Jump to:

• Peer-reviewed articles
• Scientific Presentations
• Continuing Education Presentations
• Professional Publications
• Books

Peer-reviewed articles

2024

Al Atrach,M., Phan.C-M., Jones,L. Extended release of ciprofloxacin from commercial contact lenses containing vitamin E diffusion barriers Optometry and Vision Science 2024;Online ahead of print

Arvind,A., Najappa,R., Gupta,K. K., Macedo-De-Araujo,R. J., Fadel,F. Lid wiper epitheliopathy: Topical review of current identification strategies and future perspectives Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Lid Wiper Epitheliopathy (LWE) is a recognized ocular condition affecting visual quality and ocular comfort, characterized by the damage of the marginal conjunctiva of the upper eyelid. This review critically examines the current strategies for LWE identification and explores the multifactorial etiology of LWE and its association with various ocular surface diseases. A literature review conducted on PubMed identified 67 relevant studies, which were analyzed to enhance understanding of LWE’s diagnostic criteria and its clinical implications, offering future perspectives on improving diagnostic accuracy and patient outcomes.

The association between LWE and contact lens-related discomfort is examined, with studies reporting conflicting findings regarding its prevalence and severity among soft contact lens wearers. Moreover, LWE has been linked to tear film abnormalities, altered tear composition, and eyelid margin abnormalities in non-contact lens wearers, further complicating diagnosis and management.

Current LWE grading systems, including subjective methods and semi-objective approaches, are reviewed, highlighting challenges such as subjectivity, complexity, and variability. Recent advances in LWE grading, including semi-automated methods and photographic scales, show promise but face implementation challenges in clinical settings.

The review concludes by proposing areas for further research, including investigating factors contributing to LWE onset and development, developing more sensitive diagnostic tools, and exploring the impact of LWE on ocular surface health and visual function. Standardization, validation, and innovation in grading systems are emphasized to enhance diagnostic accuracy and improve clinical outcomes for patients with LWE. Ongoing research in LWE grading is essential for addressing diagnostic challenges and optimizing assessment methodologies in clinical practice.

Aziz,A., Kuppusamy,R., Mazumder,K., Hui,A., Maulvi,F., Stapleton,F., Willcox,M. Absorption and attachment of atropine to etafilcon A contact lenses Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose: Myopia (short-sightedness) is a growing vision problem worldwide. Currently atropine eye drops are used to control the progression of myopia but these suffer from potential lack of bioavailability and low ocular residence time. Commercially available myopia control contact lenses are also used to limit myopia progression, but neither atropine nor contact lenses individually completely stop progression. Development of myopia control contact lenses which could deliver therapeutic doses of atropine is thus desirable and may provide increased efficacy. This study was designed to explore the feasibility of attaching atropine to etafilcon A contact lenses through an esterification reaction.

Methods: Carboxylic acid groups on etafilcon A contact lenses were quantified using Toluidine Blue O. The carboxylic acid groups in etafilcon A contact lenses were activated using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC-HCl) and N-hydroxysuccinimide (NHS) crosslinkers after which atropine was added to undergo potential binding via esterification. Atropine was released from lenses by alkaline hydrolysis. Reverse phase high performance liquid chromatography (HPLC) was used to detect and quantify the released atropine and its degradation products in solution. Contact lenses that had not been activated by EDC-NHS (controls) were also examined to determine the amount of atropine that could be absorbed rather than chemically bound to lenses.

Results: Each etafilcon A contact lens contained 741.1 ± 5.5 µg carboxylic acid groups which may be available for esterification. HPLC had a limit of detection for atropine of 0.38 µg/mL and for tropic acid, an atropine degradation product, of 0.80 µg/mL. The limits of quantification were 1.16 µg/mL for atropine and 2.41 µg/mL for tropic acid in NH4HCO3. The etafilcon A lenses adsorbed up to 7.69 μg atropine when incubated in a 5 mg/mL atropine solution for 24 h. However, there was no evidence that atropine could be chemically linked to the lenses, as washing in a high concentration of NaCl removed all the atropine from the contact lenses with no atropine being subsequently released from the lenses after incubating in 0.01 N NH4HCO3.

Conclusions: Etafilcon A contact lenses contain free carboxylic acids which may be an appropriate option for attaching drugs such as atropine. Etafilcon A lenses adsorbed up to 7.69 μg atropine, which would be more than enough to deliver atropine to eyes to control myopia. However, atropine could not be chemically bound to the carboxylic acids of the etafilcon A lenses using this methodology.

Bose,S., Phan,C.-M., Rizwan,M., Tse,J. W., Yim,E., Jones,L. Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material Pharmaceutics 2024;16(1):Article 26 [ Show Abstract ]

Purpose: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+).

Methods: Two GelMA+ formulations, 20% w/v, and 30% w/v concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlueTM assay and the LIVE/DEADTM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% w/v gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations.

Results: The 30% w/v GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (p < 0.05). In contrast, the 20% w/v GelMA+ degraded at a significantly faster rate (p < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% w/v GelMA+ exhibited significantly higher cell viability (p < 0.05). The 30% w/v GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (p < 0.001), corresponding to the degradation rate of the gels.

Discussion: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid.

Chow,A. H. Y., Mungalsingh,M., Thai,D., Selimos,Z., Yan,S. K., Xu,H., Jones,D. A. Suitability of multifunction devices Myah and Myopia Master for monitoring myopia progression in children and adults Ophthalmic and Physiological Optics 2024;44(5):1017-1030 [ Show Abstract ]

Purpose: To assess the feasibility of using multifunction instruments to measure axial length for monitoring myopia progression in children and adults.

Methods: Axial length was measured in 60 children (aged 6–18 years) and 60 adults (aged 19–50 years) with multifunction instruments (Myah and Myopia Master) and stand-alone biometers (Lenstar LS900 and IOLMaster 700). Repeatability (measurements by the same examiner) and reproducibility (measurements by different examiners) were computed as the within-subject standard deviation (Sw) and 95% limits of agreement (LoA). Inter-instrument agreement was computed as intraclass correlation coefficients. The threshold for detecting myopic progression was taken as 0.1 mm. Measures were repeated only in children following the administration of 1% tropicamide to determine the impact of cycloplegia on axial length.

Results: Overall, the IOLMaster 700 had the best repeatability in children (0.014 mm) and adults (0.009 mm). Repeatability Sw values for all devices ranged from 0.005 to 0.021 mm (children) and 0.003 to 0.016 mm (adults). In children, reproducibility fell within 0.1 mm 95% of the time for the Myah, Myopia Master and IOLMaster 700. Agreement among all devices was classified as excellent (ICC 0.999; 95% CI 0.998–0.999), but the 95% LoA among the Myah, Myopia Master and Lenstar LS900 was ≥0.1 mm. Cycloplegia had no statistically significant effect on axial length (all p > 0.13).
Conclusions: The Myah and Myopia Master multifunction instruments demonstrated good repeatability and reproducibility, and their accuracy was comparable to stand-alone biometers. Axial length measurements using different instruments can be considered interchangeable but should be compared with some caution. Accurate axial length measurements can be obtained without cycloplegia. The multifunction instruments Myah and Myopia Master are as well suited for monitoring myopia progression in children as the stand-alone biometers IOLMaster 700 and Lenstar LS900.

Dang,R., Ehrmann,K., Jalbert,I., Hui,A., Kang,P. Refractive power profiles of commercially available soft multifocal contact lenses for myopia control Ophthalmic and Physiological Optics 2024;Online ahead of print [ Show Abstract ]

Purpose: Lens power profiles can provide valuable insights on the imposed optical defocus and visual experience of contact lens wearers, especially in the context of myopia control. This study measured the refractive power profiles of multifocal soft contact lenses (MFCLs) currently used or that have the potential for use in myopia control using high spatial resolution aberrometry. The instrument's repeatability for determining MFCLs power profiles was also assessed.

Method: The power profiles of 10 MFCLs of various designs (centre-distance, centre-near and extended depth of focus) were measured using the Lambda-X NIMOEVO, a phase shifting Schlieren-based device. Power profiles were graphically expressed as measured power at each chord position and the maximum add power was calculated. The repeatability of the NIMOEVO was expressed as the within-subject standard deviation at each chord position for a subset of five MFCLs.

Results: The measured distance powers differed from nominal powers for more than half of the MFCLs with a definable distance zone. There were variations in the chord position of the distance and near correction zones, rate of power transitions and calculated maximum add between the MFCLs which did not depend on lens design. For half of the MFCLs, the power profile shape was inconsistent between different nominal back vertex powers of the same design. The repeatability of the NIMOEVO was dependent on the lens design, with designs featuring faster rates of power change exhibiting worse repeatability.

Conclusions: Significant differences in MFCL power profiles were found which were not adequately represented in labelling. This is likely due to the small number of parameters used to define lens power characteristics. Eye health care practitioners should be aware of potential differences in power profiles between different MFCLs, which will impact the retinal defocus introduced during lens wear and the wearer's visual experience.

Efron,N., Morgan,P., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in rigid contact lens prescribing (2000–2023): An update Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose: Rigid contact lenses have an important role in contact lens practice. The purpose of this work is to update earlier surveys by describing global trends in rigid lens fitting between 2000-2023.

Method: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023. Data relating to 342,500 fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of rigid lens fitting, defined as the fitting of any design of a contact lens manufactured in a rigid material.

Results: Overall, rigid lens prescribing increased slightly over time, from 14.2 % of lens fits in 2000 to 15.2 % in 2023 (p < 0.0001). However, post-hoc analysis shows that the change over time is best described as a decline between 2000 and 2012, followed by a steady increase subsequently. There were significant differences in rigid lens prescribing between countries (p < 0.0001). The difference between the percentage of males fitted with rigid lenses, as a proportion of all contact lenses (12.7 %), and females (12.0 %) is significant (p < 0.0001), although not clinically meaningful. Rigid lens wearers are older at fitting than soft lens wearers (38.7 vs 31.3 years,
respectively) (p < 0.0001). Analysis of 5,994 rigid lens fits prescribed currently (2019–2023) were categorised as: corneal sphere – 30 %; scleral and corneo-scleral – 28 %; corneal myopia control/orthokeratology – 21 %; and corneal complex (including toric, multifocal and monovision) – 16 %.

Conclusion: There has been a slight increase in rigid lens fitting during the second decade of this century. This increase is apparently due to a ‘repurposing’ of rigid lenses, with the growth of scleral/corneo-scleral and myopia control/orthokeratology lens fits essentially replacing conventional spherical corneal lens fits.

Efron,N., Morgan,P., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in prescribing toric soft contact lenses to correct astigmatism (2000–2023): An update Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose
There have been significant advancements in toric soft contact lens design and manufacturing technology, and increased product availability, over the past half a century. The purpose of this work is to update earlier surveys by describing international trends in toric soft lens fitting between 2000 and 2023, inclusive.

Method
An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 220,934 standard soft daily wear single vision lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of toric soft lens fitting.

Results
Overall, toric soft lens prescribing almost doubled over the time-course of this survey, from 24.4 % of standard soft daily wear single vision lens fits in 2000 to 46.2 % in 2023 (p < 0.0001). There were significant differences between countries in toric soft lens prescribing (p < 0.0001). Of all standard soft daily wear single vision contact lenses prescribed to males, 32.0 % were toric soft lenses, compared with 28.7 % for females (p < 0.0001). The mean age of toric soft lens wearers was 30.5 ± 12.5 years, compared to 27.9. ± 12.1 years for spherical soft lens wearers (p < 0.0001). Analysis of 13,582 recent toric soft lens fits (2019–2023, inclusive), in terms of material type and replacement frequency, revealed the following proportions: reusable silicone hydrogel – 51 %; daily disposable silicone hydrogel – 27 %; daily disposable hydrogel – 12 %; and reusable hydrogel – 10 %.

Conclusion
There has been a substantial increase in toric soft lens fitting throughout the 24 years of this survey, to a point whereby almost all clinically significant astigmatism is being corrected among those wearing standard soft daily wear single vision lenses.

Efron,N., Morgan,P., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in prescribing silicone hydrogel contact lenses for daily wear (2000–2023): An update Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose
Introduced around the turn of the 21st century, silicone hydrogel contact lenses alleviated hypoxic anterior eye complications due to their high oxygen transmissibility. The purpose of this work is to update earlier surveys by describing international trends in silicone hydrogel daily wear contact lens fitting between 2000 and 2023.

Method
An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023. Data relating to 260,144 daily wear soft contact lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of silicone hydrogel daily wear contact lens fitting.

Results
There has been a dramatic increase in silicone hydrogel daily wear lens fits (p < 0.0001), increasing from 2.8 % of all daily wear soft lens fits in 2000 to 73.7 % in 2023. Of all daily wear soft contact lenses prescribed to males, 44.6 % were silicone hydrogel lenses, compared with 43.5 % for females (p = 0.0146). The mean age of those wearing silicone hydrogel daily wear lenses was 32.0 ± 14.5 years, compared to 30.4 ± 13.6 years for those wearing daily wear hydrogel lenses (p < 0.0001). Between 2019–2023, the average percentage of fits was – (a) material type: silicone hydrogel – 73 %; mid-water content hydrogels – 13 %; high water content hydrogels – 9 %; and low water content hydrogels – 5 %, and (b) lens design: spherical – 44 %, toric – 32 %, multifocal – 17 %, monovision – 4 %, and ‘other’ – 3 %.

Conclusion
The dramatic increase in silicone hydrogel contact lens prescribing for daily wear has been commensurate with the introduction of multiple lens brands and an ongoing expansion of lens designs, parameters and replacement frequency options. The balance between silicone hydrogel and hydrogel lens prescribing is perhaps starting to approach an equilibrium.

Fadel,D., Macedo-de-Araújo,R. J., Barnett,M. The Patient-Physician Relationship and Role of Empathic Communication in Contact Lens Practice Journal of Contact Lens Research and Science 2024;8(1):20-36

Ganguly,S., Wulff,D., Phan,C-M., Jones,L., Tang,X. Injectable and 3D Extrusion Printable Hydrophilic Silicone-Based Hydrogels for Controlled Ocular Delivery of Ophthalmic Drugs Applied Bio Materials 2024;Online ahead of print [ Show Abstract ]

While silicone elastomers have found widespread use in the biomedical industry, 3D printing them has proven to be difficult due to the material’s slow drying time, low viscosity, and hydrophobicity. Herein, we arrested the hydrophilic silicone (HS) macrochains into a semi-interpenetrating polymer network (semi-IPN) via an in situ photogelation-assisted 3D microextrusion printing technique. The flow behavior of the pregel solutions and the mechanical properties of the printed HS hydrogels were tested, showing a high elastic modulus (approximately 15 kPa), a low tan δ, high elasticity, and delayed network rupturing. The uniaxial compression tests
demonstrated a nearly negligible permanent deformation, suggesting that the printed hybrid hydrogel maintained its elastic properties. Drug loading and diffusion in the microporous hydrogel are shown via the non-Fickian anomalous transport mechanism, leading to highly tunable loading/releasing profiles (approximately 20% cumulative release) depending on the HS concentration. The drug encapsulation exhibits exceptional stability, remaining intact without any degradation even after a storage period of 1 month. As far as we know, this is the first soft biomaterial based on HS that functions as an exceptional controlled drug delivery device.

Guthrie,S. E., Luensmann, D., Woods,J., Vega,J., Orsborn,G. Relationships Between Success Factors in Daily Disposable Multifocal Contact Lenses Clinical Optometry 2024;16157-167 [ Show Abstract ]

Purpose: To explore links between subjective comfort and vision in habitual multifocal soft contact lens (MFCL) wearers when refit with daily disposable MFCLs, to determine which factors are relevant for success with MFCLs and evaluate consistency between MFCLs of different designs.

Patients and Methods: This work examined subjective measures in a randomised, participant masked, bilateral wear crossover study at five optometry practices. Fifty-eight habitual MFCL wearers wore stenfilcon A multifocal (stenA-MF; CooperVision Inc) and delefilcon A multifocal (delA-MF; Alcon) for two-weeks. Subjective ratings included satisfaction with comfort and vision and agreement questions.

Results: Agreement with “I would like to wear this MFCL in the future” was taken to indicate success with each MFCL; agreement was significantly higher with stenA-MF. There was strong correlation between agreement responses for “I would like to wear this MFCL in the future” and “MFCL met my needs for vision” with both lenses (p< 0.01). However, it was only with stenA-MF, which had higher agreement responses to both statements (p< 0.05), that responses to these two statements correlated with satisfaction with end-of-day (EOD) comfort (p< 0.01). These differences in correlations between the two lenses are seemingly driven by greater satisfaction with stenA-MF for near and intermediate vision (p< 0.05).

Conclusion: Subjective vision and comfort were only correlated when vision met the needs of most participants. Meeting participants’ needs for vision correlated strongly with wanting to wear a MFCL. Results indicate that meeting vision needs is more important than meeting comfort needs when influencing whether presbyopic patients continue wearing MFCLs.

Jabeen,A., Luensmann,D., Woods,J., Hill,J. S., Jones,L. Evaluation of Lag of Accommodation with Full-Field Diffusion Optics Technology™ (DOT) Contrast Management Spectacle Lenses in Emmetropic Children Clinical Ophthalmology 2024;2024(18):1181-1190 [ Show Abstract ]

Purpose: To evaluate the impact on the lag of accommodation (LOA) in emmetropic children after short-term wear of full-field Diffusion Optics TechnologyTM (DOT) spectacle lenses, designed to modulate retinal contrast to control myopia progression.

Patients and Methods: This was a single-visit, prospective, randomized, subject-masked study of emmetropes (ametropes ±1.00D or less in each meridian) with no history of myopia control treatment. Unaided logMAR visual acuity was measured, and ocular dominance was determined using the sighting method. In a randomized order, participants wore plano full-field contrast management (DOT) spectacles (no clear central aperture) or control spectacles (standard single vision spectacle lenses). Each participant was given 5 minutes for adaptation to the respective lenses before open field autorefraction measurements were taken at 6 meters and 40 cm. Ten measurements were taken for each eye. Data were evaluated from the right eye and the dominant eye separately.

Results: A total of 30 participants (20 females and 10 males) with a mean age of 10.4 ± 2.8 (7 to 17) years completed the study. There was no significant difference in right eye mean LOA with contrast management spectacles 0.57 ± 0.39D versus control spectacles 0.62 ± 0.34D; Wilcoxon test, p = 0.37. For dominant eyes, LOA values were 0.60 ± 0.40D and 0.68 ± 0.33D with contrast management spectacles and control spectacles, respectively (p = 0.14). Additionally, no significant difference was observed in mean LOA between males and females or between age groups (7–11 years vs 12–17 years) for either right or dominant eyes with contrast management or control spectacles (all p > 0.05).

Conclusion: Full-field contrast management spectacle lenses had no significant effect on LOA compared to standard single vision spectacle lenses, indicating no differential impact on accommodative response over the short period of lens wear tested.

Jabeen,A., Luensmann,D., Woods,J., Hill,J., Jones,L. Evaluation of Lag of Accommodation with Full-Field Diffusion Optics Technology™ (DOT) Contrast Management Spectacle Lenses in Emmetropic Children Clinical Ophthalmology 2024;18(May):1181-1190 [ Show Abstract ]

Purpose: To evaluate the impact on the lag of accommodation (LOA) in emmetropic children after short-term wear of full-field Diffusion Optics TechnologyTM (DOT) spectacle lenses, designed to modulate retinal contrast to control myopia progression.

Patients and methods: This was a single-visit, prospective, randomized, subject-masked study of emmetropes (ametropes ±1.00D or less in each meridian) with no history of myopia control treatment. Unaided logMAR visual acuity was measured, and ocular dominance was determined using the sighting method. In a randomized order, participants wore plano full-field contrast management (DOT) spectacles (no clear central aperture) or control spectacles (standard single vision spectacle lenses). Each participant was given 5 minutes for adaptation to the respective lenses before open field autorefraction measurements were taken at 6 meters and 40 cm. Ten measurements were taken for each eye. Data were evaluated from the right eye and the dominant eye separately.

Results: A total of 30 participants (20 females and 10 males) with a mean age of 10.4 ± 2.8 (7 to 17) years completed the study. There was no significant difference in right eye mean LOA with contrast management spectacles 0.57 ± 0.39D versus control spectacles 0.62 ± 0.34D; Wilcoxon test, p = 0.37. For dominant eyes, LOA values were 0.60 ± 0.40D and 0.68 ± 0.33D with contrast management spectacles and control spectacles, respectively (p = 0.14). Additionally, no significant difference was observed in mean LOA between males and females or between age groups (7-11 years vs 12-17 years) for either right or dominant eyes with contrast management or control spectacles (all p > 0.05).

Conclusion: Full-field contrast management spectacle lenses had no significant effect on LOA compared to standard single vision spectacle lenses, indicating no differential impact on accommodative response over the short period of lens wear tested.

Jiang,Q., Zhang,Z., Niu,L., Wang,B., Fadel,D., Wei,R., Chen,Z. Changes in anterior segment after short-term scleral lens wear in healthy Chinese population Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose
To evaluate the impact of short-term scleral lens (SL) wear on anterior chamber (AC) dimension and central corneal thickness (CCT) in healthy Chinese people.

Methods
This is a prospective, daily wear study. Eligible participants were dispensed SLs to correct refractive errors. Anterior segment (AS) parameters were measured by AS optical coherence tomography (AS-OCT) before, during, and after 2 and 4 hours of lens wear. Repeated-measures analysis of variance (ANOVA) was used to analyze the changes in AS parameters over time.

Results
Twelve subjects (10 females and 2 males) with a mean age of 25.3 ± 3.8 years (ranging from 21 to 34 years) were recruited. The AC parameters, including anterior chamber depth (ACD) from the endothelium (endo-ACD), angle opening distance at 500 μm (AOD500), and trabecular-iris space area at 500 μm (TISA500), significantly decreased after wearing SLs for 4 hours (P<0.05). CCT increased by 12 μm (2.29 %) after wearing SLs for 4 hours (P=0.013).

Conclusion
This study suggests that SL wear has a significant impact on AS dimensions in patients with healthy corneas in the short term with SL in situ, but tend to recover quickly after SL removal. Further research is needed to determine whether the change in AS dimensions during SL wear affects aqueous humor (AH) outflow and causes changes in intraocular pressure (IOP).

Jin,Y., Minten,C., Jenkins,M., Jones,L., Gorbet,M. Investigation of the rhythmic recruitment of tear neutrophils to the ocular surface and their phenotypes Scientific Reports 2024;147061 [ Show Abstract ]

Hundreds of thousands of polymorphonuclear neutrophils (PMNs) are collected from the ocular surface upon waking, while few are harvested during daytime. This study aimed to investigate potential factors contributing to the circadian infiltration of tear PMNs, including changes in IL-8 and C5a in tears, and their phenotypes across different time points in a 24-h cycle. Tear PMNs were collected using a gentle eyewash after 2-h and 7-h of sleep (eye closure, EC) at night, after 2-h EC during the day, and towards the end of the afternoon. Significantly fewer cells were collected after 2-h EC during the day compared to 2-h EC at night. A positive correlation between IL-8 and PMN numbers existed, but not with C5a. Tear PMNs collected after 2-h EC at night were less degranulated and possessed a larger activation potential compared to 7-h EC. Tear PMNs from 7-h EC at night exhibited hyper-segmented nuclei and more NETosis compared to 2 h EC night, indicating an aged and activated phenotype. The diurnal-nocturnal recruitment pattern of tear PMNs may be driven by increased IL-8 in nighttime tears. Higher degranulation and NETs point to the significant activation of tear PMNs on the ocular surface during prolonged eye closure at night.

Mishra,S. K., Baidya,S., Bhattarai,A., Shrestha,S., Homagan,S., Rayamajhee,B., Hui,A., Willcox,M. Bacteriology of Endotracheal Tube Biofilms and Antibiotic Resistance: A Systematic Review Journal of Hospital Infection 2024;Online ahead of print [ Show Abstract ]

Background
Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can appear many times more resistant to antibiotics or disinfectants. This systematic review explores the prevalence and microbial profile associated with biofilm production of bacteria isolated from endotracheal tubes and its associations with antimicrobial resistance.

Methods
A comprehensive search was performed on databases PubMed, Embase, and Google Scholar for relevant articles published between January 1, 2000 and December 31, 2022. The relevant articles were exported to Mendeley Desktop 1.19.8 and screened by title and abstract, followed by full text screening based on the eligibility criteria of the study. Quality assessment of the studies was performed using the Newcastle-Ottawa Scale (NOS) customized for cross-sectional studies. Furthermore, the prevalence of antimicrobial resistance in biofilm-producers isolated from endotracheal tube specimens was investigated.

Results
Twenty studies encompassing 981 endotracheal tubes met the eligibility criteria. Pseudomonas spp. and Acinetobacter spp. were predominant isolates among the biofilm producers. These biofilms provided strong resistance against commonly used antibiotics. The highest resistance rate observed in Pseudomonas spp. was against fluoroquinolones whereas the least resistance was seen against piperacillin-tazobactam. A similar trend of susceptibility was observed in Acinetobacter spp. with a very high resistance rate against fluoroquinolones, third-generation cephalosporins and carbapenems.

Conclusion
Endotracheal tubes were associated with colonisation by biofilm forming bacteria with varying levels of antimicrobial resistance. Biofilms may promote the occurrence of recalcitrant infections in endotracheal tubes which need to be managed with appropriate protocols and antimicrobial stewardship. Research focus should shift towards meticulous exploration of biofilm-associated infections to improve detection and management.

Mohseni,M., Shokrollahi,P., Barzin, J. Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release International Journal of Biological Macromolecules 2024;263, Part 1(April):Art No 130266

Morgan,P., Efron,N., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in daily disposable contact lens prescribing (2000–2023): An update Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose
Daily disposable contact lenses offer numerous benefits in terms of ocular health and wearer convenience. The purpose of this work is to update earlier surveys by describing global trends in daily disposable lens fitting between 2000 and 2023.

Method
An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 265,106 daily wear soft lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of daily disposable lens fitting.

Results
Overall, daily disposable lens prescribing increased over time, from 17.1 % of daily wear soft lens fits in 2000 to 46.7 % in 2023 (p < 0.0001). There were significant differences between countries in daily disposable lens prescribing (p < 0.0001), and between the percentage of males fitted with daily disposable lenses, as a proportion of all daily wear soft lenses (37.2 %), compared to females (35.2 %) (p < 0.0001). Daily disposable lens wearers are slightly younger at fitting than reusable soft lens wearers (31.0 vs 31.2 years, respectively) (p < 0.0001), although this difference is not clinically meaningful. Analysis of 50,240 daily wear soft lenses fitted recently (2019–2023) were found to be prescribed for the following replacement frequencies: daily – 47 %; monthly – 42 %; 1–2 weekly – 9 %; and ≥3 monthly – 2 %.

Conclusion
There has been a substantial increase in daily disposable lens fitting throughout the first 24 years of this century. The gradual nature of this increase is commensurate with the staged introduction of daily disposable lens designs and expanded parameter ranges over the survey period.

Morgan,P., Efron,N., Woods,C. A., Jones,D. A., Jones,L., Nichols,J. International trends in prescribing extended wear soft contact lenses (2000–2023): An update Contact Lens Anterior Eye 2024;Online ahead of print [ Show Abstract ]

Purpose
Extended wear has long been considered as the ultimate contact lens modality in terms of user convenience. The purpose of this work is to update earlier surveys by describing international trends in extended wear soft lens fitting between 2000 and 2023, inclusive.

Method
An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 282,142 soft contact lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of extended wear soft lens fitting.

Results
Over the duration of the work there was a very small decrease in the prescribing of extended wear soft lenses (p < 0.0001). More detailed inspection shows that prescribing of these lenses steadily increased from 5.8 % of all soft lens fits in 2000 to 11.6 % in 2007, then steadily decreased to 5.2 % in 2023. Of all soft contact lenses prescribed to males, 9.2 % were fitted for extended wear, compared with 6.7 % for females (p < 0.0001). The mean age of extended wear soft lens wearers at fitting was 34.7 ± 14.7 years, compared to 31.1. ± 14.10 years for daily soft lens wearers (p < 0.0001). Analysis of 1,948 recent extended wear soft lens fits (2019–2023, inclusive), in terms of material type, revealed that, on average, 86 % and 14 % of extended wear soft lenses were fitted using silicone hydrogel and hydrogel materials, respectively.

Conclusion
A modest increase in extended wear soft lens prescribing from 2000 to 2007 corresponded with the introduction of high oxygen transmissibility silicone hydrogel lenses. However, prescribing of this lens type declined thereafter, probably due to ongoing concerns over their increased rate of microbial keratitis, resulting in a prescribing rate in 2023 (5.2%) that was little different to that observed in 2000 (5.8%).

Navascues-Cornago,M., Guthrie,S., Morgan,P., Woods,J. Determination of the Minimal Clinically Important Difference (MCID) for Ocular Subjective Responses Transl Vis Sci Technol 2024;13(8):28 [ Show Abstract ]

Purpose: To determine the minimal clinically important difference (MCID) for contact lens (CL)-related subjective responses and explore whether MCID values differ between subjective responses and study designs.
Methods: This was a retrospective analysis of data from seven one-week bilateral crossover studies and 14 one-day contralateral CL studies. For comfort, dryness, vision, or ease of insertion, participants rated on a 0-100 visual analogue scale (VAS) and indicated lens preference on a five-point Likert scale featuring strong, slight, and no preferences. For each criterion, four MCID estimates were calculated and averaged: mean VAS score difference for "slight preference," lower limit of 95% confidence interval VAS score difference for "slight preference," difference in mean VAS score difference between "slight" and "no preference" and 0.5 standard deviation of VAS scores.
Results: The four calculation methods generated a small range of MCID values. For bilateral studies, the averaged MCID was 7.2 (range 5.4-8.8) for comfort, 8.1 (5.2-10.6) for dryness, 7.1 (5.5-9.3) for vision and 7.6 (6.0-10.5) for ease of insertion. For contralateral studies, the averaged MCID was 6.9 (6.1-7.6) for comfort at insertion and 7.5 (6.8-8.2) for end-of-day comfort.
Conclusions: This work demonstrated very similar MCID values across subjective responses and study designs, in a population of habitual soft CL wearers. In all cases, MCID values were on average seven units on a 0 to 100 VAS.
Translational relevance: This work provides MCID values which are important for interpreting ocular subjective responses and planning clinical studies.

Phan,C. M., Chan,V. W. Y., Drolle,E., Hui,A., Ngo,W., Bose,S., Shows,A., Liang,S., Sharma,B., Subbaraman,L., Zheng,Y., Shi,X., Wu,J., Jones,L. At this time no specific clinical outcome instrument can be recommended on the basis of an evidence-based review of the literature, but the CLDEQ-8 best approaches the most validated measure Contact Lens Anterior Eye 2024;47(2):102129 [ Show Abstract ]

Purpose
To evaluate the in vitro wettability and coefficient of friction of a novel amphiphilic polymeric surfactant (APS), poly(oxyethylene)–co-poly(oxybutylene) (PEO-PBO) releasing silicone hydrogel (SiHy) contact lens material (serafilcon A), compared to other reusable SiHy lens materials.

Methods
The release of fluorescently-labelled nitrobenzoxadiazole (NBD)-PEO-PBO was evaluated from serafilcon A over 7 days in a vial. The wettability and coefficient of friction of serafilcon A and three contemporary SiHy contact lens materials (senofilcon A; samfilcon A; comfilcon A) were evaluated using an in vitro blink model over their recommended wearing period; t = 0, 1, 7, 14 days for all lens types and t = 30 days for samfilcon A and comfilcon A (n = 4). Sessile drop contact angles were determined and in vitro non-invasive keratographic break-up time (NIKBUT) measurements were assessed on a blink model via the OCULUS Keratograph 5 M. The coefficient of friction was measured using a nano tribometer.

Results
The relative fluorescence of NBD-PEO-PBO decreased in serafilcon A by approximately 18 % after 7 days. The amount of NBD-PEO-PBO released on day 7 was 50 % less than the amount released on day 1 (6.5±1.0 vs 3.4±0.5 µg/lens). The reduction in PEO-PBO in the lens also coincided with an increase in contact angles for serafilcon A after 7 days (p 0.05). The other contact lens materials had stable contact angles and NIKBUT over their recommended wearing period (p > 0.05), with the exception of samfilcon A, which had an increase in contact angle after 14 days as compared to t = 0 (p < 0.05). Senofilcon A and samfilcon A also showed an increase in coefficient of friction at 14 and 30 days, respectively, compared to their blister pack values (p < 0.05).

Conclusion
The results indicate that serafilcon A gradually depletes its reserve of PEO-PBO over 1 week, but this decrease did not significantly change the lens performance in vitro during this time frame.

Qiu,S. X., Fadel,D., Hui,A. Scleral Lenses for Managing Dry Eye Disease in the Absence of Corneal Irregularities: What Is the Current Evidence? Journal of Clinical Medicine 2024;13(13):3838 [ Show Abstract ]

Scleral lenses (SLs) are large-diameter rigid contact lenses that are a mainstay treatment for eyes with corneal irregularities. In recent years, there has been increased interest in the role of managing dry eye disease (DED) with SLs, as many patients with DED have reported symptomatic relief with SL wear. The role of SLs for DED management when there are associated corneal irregularities is supported by individual case reports and studies. This has prompted practitioners to begin advocating using SLs in DED cases, even in the absence of associated corneal irregularities and other ocular surface diseases (OSDs). There have also been discussions on potentially placing SLs earlier in the treatment hierarchy of DED, where it currently sits at a more advanced level of intervention (Step 3) in the TFOS DEWS II Report. This review will present the currently available, albeit sparse, evidence that supports and suggests this practice, as well as ancillary evidence supporting the purported benefits of SL wear in DED. The advantages of SL wear, such as corneal healing, absence of tear evaporation and contact lens dehydration, and improved visual acuity with associated increased wear comfort, and how this will benefit DED patients will be explored. Conversely, the challenges associated with fitting SLs in DED patients, including increased midday fogging, poor wettability, and subjective patient satisfaction, will also be presented, as well as a discussion on the key considerations for SL fitting in this population. Overall, while more research is needed to support the use of SLs in DED patients without associated corneal irregularities and other forms of OSD, the use of these lenses may prove to have a potentially wider role given their reported ancillary benefits in these populations.

Sara,M. Hui,A., Yasir,M., Hari Kumar,P., Kalaiselvan,P., Willcox,M. Intrastromal Corneal Ring Implants Associated Bacterial Infections Current Eye Research 2024;Online ahead of print [ Show Abstract ]

Purpose: This study examines the incidence of infection and resistance associated with Intracorneal Ring Segment (ICRS) implantation, a common outpatient surgical treatment for correcting refractive errors and corneal ectatic diseases. Although ICRS procedures are typically safe and reversible, there is a low but notable risk of microbial infections, which require prompt and sometimes invasive treatment.

Methods: Three electronic databases, PubMed, Web of Science (WoS), and Scopus, were utilised to search for literature according to PRISMA guidelines to identify infections related to the implantation of ICRS in the cornea between January 2000 and December 2022.

Results: Gram-positive organisms were involved in 86% of cases: 35.7% S. aureus, 25% coagulase-negative staphylococci species, 17.8% streptococci and 7.1% Nocardia species. Less commonly recorded were Gram-negative bacteria (14%), with Pseudomonas aeruginosa (circa 10%) and Klebsiella pneumonia (4%) being the most common Gram-negative bacteria. In rare cases, fungi have also been reported. ICRS-related bacterial infections can be categorised into early or late onset. Early onset infection typically manifests within the first few weeks after implantation and is often associated with contamination during surgery, unhygienic practices, or inadequate sterilisation techniques. On the other hand, late-onset infection may develop months or even years after the initial procedures and may be associated with persistent bacterial colonisation, secondary infections, or prolonged use of prophylactic antibiotics. S aureus is encountered in both early and late-onset infections, while Nocardia species and K. pneumoniae have generally been reported to occur in late-onset infections. In addition, vision recovery from S. aureus infections tends to be poor compared to other bacterial infections.

Conclusion: S. aureus is a predominant pathogen that often requires surgical intervention with poor outcomes. Early infections result from incision gaps and ring segment rubbing, while late infections are linked to prolonged antibiotic use. Further research is needed on novel antimicrobial ICRS to procure the vision.

Wolffsohn,J. S., Berkow,D., Chan,K. Y., Chaurasiya,S. K., Fadel,D., Haddad,M., Imane, T., Jones,L., Sheppard,A. L., Vianya-Estopa,M., Walsh,K., Woods,J., Zeri,F., Morgan,P. B. BCLA CLEAR Presbyopia: Evaluation and diagnosis Contact Lens Anterior Eye 2024;47(4):102156 [ Show Abstract ]

It is important to be able to measure the range of clear focus in clinical practice to advise on presbyopia correction techniques and to optimise the correction power. Both subjective and objective techniques are necessary: subjective techniques (such as patient reported outcome questionnaires and defocus curves) assess the impact of presbyopia on a patient and how the combination of residual objective accommodation and their natural DoF work for them; objective techniques (such as autorefraction, corneal topography and lens imaging) allow the clinician to understand how well a technique is working optically and whether it is the right choice or how adjustments can be made to optimise performance. Techniques to assess visual performance and adverse effects must be carefully conducted to gain a reliable end-point, considering the target size, contrast and illumination. Objective techniques are generally more reliable, can help to explain unexpected subjective results and imaging can be a powerful communication tool with patients. A clear diagnosis, excluding factors such as binocular vision issues or digital eye strain that can also cause similar symptoms, is critical for the patient to understand and adapt to presbyopia. Some corrective options are more permanent, such as implanted inlays / intraocular lenses or laser refractive surgery, so the optics can be trialled with contact lenses in advance (including differences between the eyes) to better communicate with the patient how the optics will work for them so they can make an informed choice.

Wong,K-Y., Liu,Y., Phan,C-M., Jones,L., Wong,M-S., Liu,J. Selection of DNA aptamers for sensing drugs treating eye disease: atropine and timolol maleate Sensors & Diagnostics 2024;Online ahead of print [ Show Abstract ]

Effective monitoring of ocular drugs is crucial for personalized medicine and improving drug delivery efficacy. However, traditional methods face difficulties in detecting low drug concentrations in small volumes of ocular fluid, such as that found on the ocular surface. In this study, we used capture-SELEX to select aptamers for two commonly used ocular drugs, timolol maleate and atropine. We identified TMJ-1 and AT-1 aptamers with binding affinities of 3.4 μM timolol maleate and 10 μM atropine, respectively. Our label-free TMJ-1 biosensor using thioflavin T staining achieved a limit of detection (LOD) of 0.3 μM for timolol maleate. The AT-1 biosensor showed an LOD of 1 μM for atropine, and exhibited a 10-fold higher sensitivity compared to UV-visible spectroscopy. Future research in this area holds promise in enhancing drug delivery monitoring and improving the treatment of ocular diseases.

Wu,T.-Y., Huang,C.-C., Tsai,H.C., Lon,T.-K., Chen,P.-Y., Darge,H. F., Hong,Z.-X., Ham,H.-J., Lin,S.-Z., Lai,J.-Y., Chen,Y.-S. Mucin-mediated mucosal retention via end-terminal modified Pluronic F127-based hydrogel to increase drug accumulation in the lungs Biomaterials Advances 2024;Jan(156):213722 [ Show Abstract ]

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. β-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.

2023

Abdi,B., Mofidfar,M., Hassanpout,F., Cilingir,E. K., Kalajahi,S., Milani,P. K., Ghanbarzadeh,M., Fadel,D., Barnett,M., Ta,C. N., Leblanc,R. M., Chauhan,A., Abbasi,F. Therapeutic contact lenses for the treatment of corneal and ocular surface diseases: Advances in extended and targeted drug delivery International Journal of Pharmaceutics 2023;638(May):122740 [ Show Abstract ]

The eye is one of the most important organs in the human body providing critical information on the environment. Many corneal diseases can lead to vision loss affecting the lives of people around the world. Ophthalmic drug delivery has always been a major challenge in the medical sciences. Since traditional methods are less efficient (∼5%) at delivering drugs to ocular tissues, contact lenses have generated growing interest in ocular drug delivery due to their potential to enhance drug bioavailability in ocular tissues. The main techniques used to achieve sustained release are discussed in this review, including soaking in drug solutions, incorporating drug into multilayered contact lenses, use of vitamin E barriers, molecular imprinting, nanoparticles, micelles and liposomes. The most clinically relevant results on different eye pathologies are presented. In addition, this review summarizes the benefits of contact lenses over eye drops, strategies for incorporating drugs into lenses to achieve sustained release, results of in vitro and in vivo studies, and recent advances in the commercialization of therapeutic contact lenses for allergic conjunctivitis.

Akbari,E., Imani,R., Shokrollahi,P., Keshel,S. H. Corneal sustained delivery of hyaluronic acid from nanofiber-containing ring-implanted contact lens Journal of Biomaterials Application 2023;37(6):992-1006 [ Show Abstract ]

Dry eye syndrome, as a persist corneal epithelial defect (PED), is an inconvenient ocular disorder that is generally treated by high-dosage, conventional eye drops. Addressing low efficacy and rather restricted bioavailability of the conventional eye drops, drug-eluting contact lenses (CLs) are widely used as alternatives in ophthalmic drug delivery applications. In the present study, a nanofiber-containing ring implant poly (vinyl alcohol) (PVA) hydrogel is designed as a carrier for hyaluronic acid (HA) delivery. hyaluronic acid is physically encapsulated in a nanofiber-containing ring-shaped hydrogel with a 2 mm width that is implanted in the final CLs hydrogel. The designed CL has 59% porosity, 275% swelling ratio and undergoes no weight loss at physiological conditions in14 days. In-vitro release studies were performed on the CLs with and without nanofibers. The results showed that nanofiber incorporation in the designed CL was highly influential in decreasing burst release and supported sustained release of HA over 14 days. In addition, nanofiber incorporation in the designed system strengthened the lens, and the young modulus of the PVA hydrogel increased from 6 to 10 kPa. Cell viability study also revealed no cell cytotoxicity and cell attachment. Overall, the study demonstrated the effective role of nanofibers in the physical strengthening of the CL. Also, the designed system holds promise as a potential candidate for HA delivery over an extended period for treating dry eye syndrome.

Bitton,E., Jones,D., Wittich,W. Financial Inequities in Optometric Education in Canada: A Comparison of Two Optometry Programs Optometry and Vision Science 2023;Online ahead of print [ Show Abstract ]

Significance: The advancing age of the population will require increased access to eyecare services to manage eye diseases and vision correction. Optometric education requires a sound financial plan to manage student debt. This study evaluates the financial inequalities of optometric programs in Canada, and how this may impact the provision of eyecare professionals.

Purpose: The objective of this study was to compare the financial inequities in Optometric education in Canada from the 2020 graduating class.

Methods: A cross-sectional study assessed monetary variables related to the study of optometry in Canada, including academic and personal expenses, and overall debt and expenses related to the COVID-19 lockdown for the 2020 graduating class.

Results: 108 optometry students from the 2020 graduating classes of the University of Montreal and the University of Waterloo responded, with 68 (53 F:15 M, age 25.66, SD = 2.01) completing the study. Waterloo students spent more years in university (P < .001); had higher academic fees (P <.001); spent more on travelling to their family residence (P =.007) and received more provincial (P = .002) and federal (P <.001) loans than Montreal students. Overall debt prior to optometry was similar amongst students but differed (P <.001) at the end of their program, with Waterloo students having a higher debt burden.

Conclusions: There is a financial inequity in optometric education in Canada depending on the chosen program. Cumulative optometry student debt for the 2020 graduating class in Canada ranges from $CAN 0 to 189,000 with an average of $CAN 65,800 and a median of $CAN 50,000. The results of this study can assist financial, government agencies and future optometry students to better understand the financial burdens and establish a financial plan to study optometry in Canada, to respond to the growing eyecare needs of the public.

Caffery,B., Pucker,A., Chidi-Egboka,C., Obinwanne,C. J., Karkness,B., Carnt,N. A., Ng,A. Y. Lubricating drops for contact lens discomfort in adults Cochrane Database of Systematic Reviews 2023 (5):CD015751 [ Show Abstract ]

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To determine the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults.

Craig,J. P., Alves,M., Wolffsohn,J., Downie,L. E., Efron,N., Galor,A., Gomes,J. A. P., Jones,L., Markoulli,M., Stapleton,F., Starr,C. E., Gallant Sullivan,A., Willcox,M. D. P., Sullivan,D. A. TFOS lifestyle report introduction: A lifestyle epidemic – Ocular surface disease Ocular Surface 2023;28(April):304-309 [ Show Abstract ]

Lifestyle defines how a person lives. While the way we live can impact our environment, thed environment can influence the way we live, and both can affect our health. The ocular surface, and in particular the tear film, is susceptible to modifications due to its external (e.g. environmental conditions, lifestyle and societal challenges, and the digital environment), applied (e.g. contact lens wear and cosmetics) or internal (e.g. nutrition, and elective medications and procedures) environments. Consequently, it is critical for clinicians to understand the impact of lifestyle choices on the ocular surface so that they can communicate with their patients to optimise their health and, wherever possible, institute preventative steps to mitigate potential health risk factors.

To increase awareness of the potential impacts of lifestyle choices on ocular surface health, the Tear Film & Ocular Surface Society (TFOS) launched the TFOS Workshop entitled “A Lifestyle Epidemic: Ocular Surface Disease.” Consistent with prior TFOS Workshops [[1], [2], [3], [4]], the aim was to review existing literature, to identify gaps in knowledge and to propose future directions for research, with the long-term goal of improving the lives of individuals affected by ocular surface disease around the world.

Under the leadership of the Workshop Chair Jennifer Craig, Vice Chair Monica Alves, and Organizer David Sullivan, a Steering Committee was formed (Table 1) to plan and execute this TFOS Lifestyle Workshop. The Steering Committee was committed to an evidence-based approach and a process of open communication, dialogue and transparency, to achieve a consensus concerning the relationship(s) between lifestyle factors and their impact on ocular surface disease.

Craig,J., Alves,M., Wolffsohn,J., Downie,L., Efron,N., Galor,A., Gomes,J., Jones,L., Markoulli,M., Stapleton,F., Starr,C., Sullivan,A., Willcox,M., Sullivan,D TFOS Lifestyle Report Executive Summary: A Lifestyle Epidemic - Ocular Surface Disease Ocular Surface 2023;30(October):240-253 [ Show Abstract ]

The Tear Film & Ocular Surface Society (TFOS) Workshop entitled ‘A Lifestyle Epidemic: Ocular Surface Disease’ was a global initiative undertaken to establish the direct and indirect impacts of everyday lifestyle choices and challenges on ocular surface health. This article presents an executive summary of the evidence-based conclusions and recommendations of the 10-part TFOS Lifestyle Workshop report. Lifestyle factors described within the report include contact lenses, cosmetics, digital environment, elective medications and procedures, environmental conditions, lifestyle challenges, nutrition, and societal challenges. For each topic area, the current literature was summarized and appraised in a narrative-style review and the answer to a key topic-specific question was sought using systematic review methodology. The TFOS Lifestyle Workshop report was published in its entirety in the April 2023 and July 2023 issues of The Ocular Surface journal. Links to downloadable versions of the document and supplementary material, including report translations, are available on the TFOS website: http://www.TearFilm.org.

Efron,N., Morgan,P., Jones,L., Nichols,J. Who cites optometry journals? Journal of Optometry 2023;Online ahead of print [ Show Abstract ]

Purpose
This work seeks to identify the most impactful journals, papers, authors, institutions, and countries that cite optometry journal articles.

Methods
The Scopus database was searched for papers citing at least one article published in any of the 18 optometry journals included in that database (i.e. ‘optometry articles’). The 10 most highly cited papers that cite optometry journal articles were determined from 82,830 papers found. A h-index for “optometry journal citations” (the hOJC-index) was derived for each entity in the categories of journals, papers, authors, institutions and countries to serve as a measure of impact.

Results
The hOJC-index of the body of papers citing optometry journal articles is 370. Papers citing optometry journal articles have themselves been cited 2,054,816 times. Investigative Ophthalmology & Visual Science (hOJC = 154) is the most impactful journal citing optometry articles and Optometry and Vision Science the most prolific (5310 papers). The most impactful paper citing optometry journal articles (5725 citations) was published in Journal of Clinical Epidemiology. Ophthalmologist Seang Mei Saw (hOJC = 69) is the most impactful author and optometrist Nathan Efron is the most prolific (288 papers). Harvard University (hOJC = 127) is the most impactful and UNSW Sydney is the most prolific institution (1761 papers). The United States is the most impactful and prolific nation (hOJC = 313; 28,485 papers).

Conclusions
Optometry journal articles are cited extensively by optometrists, ophthalmologists, and vision scientists world-wide, as well as authors from a broad spectrum of non-ophthalmic research domains. This work confirms the utility and influence of optometry journals.

Fadel,D. Medmont Meridia™: Much More Than a Corneal Topographer Clinical Optometry 2023;15 283-301 [ Show Abstract ]

In recent years, advanced diagnostic instruments have become widely available in optometric practices, offering various functions that optimize clinical information gathering. This article focuses on the Medmont Meridia™, a state-of-the-art multipurpose diagnostic device with corneal topography and cutting-edge features. Corneal topography is pivotal in the early diagnosis of corneal disorders, determining baseline ocular surface assessment, helping in contact lens fitting, and monitoring ocular health over time. The Medmont Meridia boasts Placido-disc-based imaging with extensive corneal coverage. Furthermore, the Meridia accurately measures the horizontal visible iris diameter, pupil diameter, and palpebral fissure width, which assists in making contact lens parameter decisions. Additionally, it offers sagittal height data for scleral lens design and first lens selection, streamlining the fitting process. Beyond its topography capabilities, the Meridia excels as a comprehensive dry eye assessment tool. With features like tear meniscus height, tear film surface quality, and meibography capabilities, it aids in diagnosing dry eye and monitoring its progression. The device also provides customizable dry eye reports with integrated grading scales and questionnaires, making dry eye management, patient education, and compliance more accessible. In conclusion, the Medmont Meridia consolidates a multitude of examination tools in a single instrument, enhancing practice efficiency and elevating patient care and communication. Its versatility and accuracy make it an invaluable asset in optometric practices worldwide.

Fadel,D., Gildea,C. Case Report: Remote Scleral Lens Fitting for High Toric Scleras in a Keratoconus Patient Optometry and Vision Science 2023;100(12):876-881 [ Show Abstract ]

SIGNIFICANCE
Technology plays a crucial role in customizing scleral lenses and improving lens alignment, especially in challenging scleral shapes. In addition, remote fitting technology allows optometrists to extend their expertise globally, empowering patients to access to customized lenses without travel expenses.

PURPOSE
The objective of this study was to document the difficulties encountered in fitting a scleral lens in a patient with keratoconus and pronounced scleral toricity. In addition, the study aimed to present the successful remote fitting achieved by using advanced technology.

CASE REPORT
An Irish male patient diagnosed with keratoconus exhibited high scleral toricity. Generally, keratoconus eyes often exhibit significant scleral asymmetry associated with cone decentration and disease severity. Improperly aligned scleral lenses can lead to regional changes in scleral shape, lens decentration, discomfort, and visual disturbances. Indeed, previous scleral lens fits were unsuccessful because of these issues. Corneoscleral profilometry was acquired in Ireland and then used in Italy to design customized lenses, which were then delivered to the patient's optometrist in Ireland. The first lenses designed and delivered demonstrated excellent overall performance without requiring adjustments.

CONCLUSIONS
This report highlights the importance of corneoscleral profilometry to increase efficiency and reduce lens reorders and chair time, and the remote fitting in overcoming barriers to accessing specialized lens fitting.

Huynh,C. B., Nagaarudkumaran,N., Kalyaanamoorthy,S., Ngo,W. In Silico and In Vitro Approach for Validating the Inhibition of Matrix Metalloproteinase-9 by Quercetin Eye & Contact Lens 2023;49(5):193-198 [ Show Abstract ]

Purpose:
To validate the mechanism and inhibitory activity of quercetin against matrix metalloproteinase-9 (MMP-9) using a hybrid in silico and in vitro approach.

Methods:
The structure of MMP-9 was obtained from the Protein Data Bank, and the active site was identified using previous annotations from the Universal Protein Resource. The structure of quercetin was obtained from ZINC15. Molecular docking was performed to quantify the binding affinity of quercetin to the active site of MMP-9. The inhibitory effect of various concentrations of quercetin (0.0025, 0.025, 0.25, 1.0, and 1.5 mM) on MMP-9 was quantified using a commercially available fluorometric assay. The cytotoxicity of quercetin to immortalized human corneal epithelial cells (HCECs) was quantified by obtaining the metabolic activities of the cells exposed to various concentrations of quercetin for 24 hr.

Results:
Quercetin interacts with MMP-9 by binding within the active site pocket and interacting with residues LEU 188, ALA 189, GLU 227, and MET 247. The binding affinity predicted by molecular docking was −9.9 kcal/mol. All concentrations of quercetin demonstrated significant inhibition of MMP-9 enzyme activity (all P0.99).

Conclusions:
Quercetin inhibited MMP-9 in a dose-dependent manner and was well-tolerated by HCECs, suggesting a potential role in therapy for diseases with upregulated MMP-9 as part of its pathogenesis.

Jones,L., Efron,N., Bandamwar,K., Barnett,M., Jacobs,D. S., Jalbert,I., Pult,H., Rhee,M. K., Sheardown,H., Shovlin,J. P., Stahl,U., Sranila,A., Tan,J. Tavazzi,S., Ucakhan,O. O., Willcox,M. D. P., Downie,L. TFOS lifestyle: Impact of contact lenses on the ocular surface Ocular Surface 2023;29(July):175-219 [ Show Abstract ]

Several lifestyle choices made by contact lens wearers can have adverse consequences on ocular health. These include being non-adherent to contact lens care, sleeping in lenses, ill-advised purchasing options, not seeing an eyecare professional for regular aftercare visits, wearing lenses when feeling unwell, wearing lenses too soon after various forms of ophthalmic surgery, and wearing lenses when engaged in risky behaviours (e.g., using tobacco, alcohol or recreational drugs). Those with a pre-existing compromised ocular surface may find that contact lens wear exacerbates ocular disease morbidity. Conversely, contact lenses may have various therapeutic benefits. The coronavirus disease-2019 (COVID-19) pandemic has impinged upon the lifestyle of contact lens wearers, introducing challenges such as mask-associated dry eye, contact lens discomfort with increased use of digital devices, inadvertent exposure to hand sanitizers, and reduced use of lenses. Wearing contact lenses in challenging environments, such as in the presence of dust and noxious chemicals, or where there is the possibility of ocular trauma (e.g., sport or working with tools) can be problematic, although in some instances lenses can be protective. Contact lenses can be worn for sport, theatre, at high altitude, driving at night, in the military and in space, and special considerations are required when prescribing in such situations to ensure successful outcomes. A systematic review and meta-analysis, incorporated within the review, identified that the influence of lifestyle factors on soft contact lens dropout remains poorly understood, and is an area in need of further research. Overall, this report investigated lifestyle-related choices made by clinicians and contact lens wearers and discovered that when appropriate lifestyle choices are made, contact lens wear can enhance the quality of life of wearers.

Nichols,J. J., Morgan,P. B., Jones,L. W., Efron, N Bibliometric Analysis of Ophthalmic Journals JAMA Ophthalmology 2023;141(7):651-657 [ Show Abstract ]

KEY POINTS
Question: What articles, journals, authors, institutions, and countries in the ophthalmic literature are the most highly cited and prolific and have the highest h-index for ophthalmic journal articles?

Findings: In this qualitative study, the h-index for ophthalmic journal articles was determined to be 494, which appeared comparable with the journal literature of other medical disciplines.

Meaning: While these analyses excluded ophthalmology articles in general medical journals, they suggest a strong ophthalmic research base underpins eye care, with ophthalmology having the highest h-index across a range of ophthalmic and vision disciplines contributing to this literature.

ABSTRACT
Importance: The primary vehicle for reporting and testing advances in eye care is refereed ophthalmic journals, which can be characterized using targeted bibliometric analyses.

Objective: To identify all ophthalmic journals and evaluate citation metrics relating to articles, journals, authors, institutions, and countries published therein.

Design and Setting: A bibliometric analysis was undertaken of all ophthalmic journals included in the Scopus database (Elsevier). The search was restricted to all article types published in ophthalmic journals in English from inception through November 18, 2022. After excluding general medical journals, journals published in a language other than English, and spurious titles unrelated to the ophthalmic field, the Scopus database was found to list 335 ophthalmic journal titles that have published 471 184 articles, constituting the data set for this analysis. The 20 most highly cited articles were identified. Rank-order lists by article count were assembled for journals, authors, institutions, and countries.

Main Outcomes and Measures: An h-index for ophthalmic journal articles was derived from citations and article counts for each constituent of each category.

Results: The h-index for ophthalmic journal articles was determined to be 494. The journal with the highest h-index was Ophthalmology (h-index, 297). The journal with the greatest number of articles was American Journal of Ophthalmology (38 441 articles). The most highly cited article was by Quigley and Broman, 2006 (5147 citations), concerning the epidemiology of glaucoma. The author with the highest h-index for ophthalmic journal articles was Ronald Klein, MD (h-index, 126), and the most prolific was Carol L. Shields, MD (1400 articles). Johns Hopkins University (h-index, 215) was the institution with the highest h-index for ophthalmic journal articles, and Harvard University was the most prolific (10 071 articles). The United States was the nation with the highest h-index for ophthalmic journal articles (h-index, 444) and was the most prolific (180 017 articles).

Conclusions and Relevance: In this study, the most highly cited articles published in ophthalmic journals were revealed, as well as the leading journals, authors, institutions, and countries. While excluding ophthalmology articles in general medical journals, this investigation affords a means of identifying highly cited authors, institutions, and countries which individuals or institutions can use as a guide regarding contributions to the field.

Nichols,J. J., Morgan,P. B., Jones,L. W., Efron, N The history of optometry journals from a bibliometric perspective Hindsight 2023;54(2):36-43 [ Show Abstract ]

The rich history of optometric journal publications has been well documented, but the scientific impact of all optometry journals over all time has not been published. This work aims to determine the most impactful papers, authors, institutions and countries publishing in optometry journals. A h-index for “optometry journal publications” (the “hOJP-index”) was derived for each constituent of each category to serve as a measure of impact. The hOJP-index for the 34,565 papers published in all optometry journals is 136; these papers have been cited 294,239 times. Optometry and Vision Science is the most impactful and prolific journal (hOJP=118; n=13,095 papers). The most highly cited paper, by Richard Armstrong, is entitled “When to use the Bonferroni correction” (1,172 citations). Australian optometrist Nathan Efron is the most impactful and prolific author (hOJP=41; n=273). UNSW Sydney and the University of California, Berkeley are the most impactful institutions (both hOJP=58), and UNSW Sydney is the most prolific (n=963). The most impactful and prolific nation is the United States (hOJP=109; n=12,050). This quantitative bibliometric analysis demonstrates an impactful optometric research base enshrined in optometry journals.

Pereira-da-Mota,A. F., Vivero-Lopez, M., Garg,P., Phan,C-M., Concheiro,A., Jones,L., Alvarez-Lorenzo,C. In vitro–in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model Drug Delivery and Translational Research 2023;13(4):1116-1127 [ Show Abstract ]

There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studies.

Phan,C. M., Ross,M., Fahmy,M., McEwen,B., Hofmann,I., Chan,V. Clark-Baba,C., Jones,L. Evaluating Viscosity and Tear Breakup Time of Contemporary Commercial Ocular Lubricants on an In Vitro Eye Model Translational Vision Science & Technology 2023;12(6):29 [ Show Abstract ]

Purpose: To evaluate the link between the viscosity of ophthalmic formulation and tear film stability using a novel in vitro eye model.

Methods: The viscosities and noninvasive tear breakup time (NIKBUT) of 13 commercial ocular lubricants were measured to evaluate the correlation between viscosity and NIKBUT. The complex viscosity of each lubricant was measured three times for each angular frequency (ranging from 0.1 to 100 rad/s) using the Discovery HR-2 hybrid rheometer. The NIKBUT measurements were performed eight times for each lubricant using an advanced eye model mounted on the OCULUS Keratograph 5M. A contact lens (CL; ACUVUE OASYS [etafilcon A]) or a collagen shield (CS) was used as the simulated corneal surface. Phosphate-buffered saline was used as a simulated fluid.

Results: The results showed a positive correlation between viscosity and NIKBUT at high shear rates (at 10 rad/s, r = 0.67) but not at low shear. This correlation was even better for viscosities between 0 and 100 mPa*s (r = 0.85). Most of the lubricants tested in this study also had shear-thinning properties. OPTASE INTENSE, I-DROP PUR GEL, I DROP MGD, OASIS TEARS PLUS, and I-DROP PUR had higher viscosity in comparison to other lubricants (P < 0.05). All of the formulations had a higher NIKBUT than the control (2.7 ± 1.2 seconds for CS and 5.4 ± 0.9 seconds for CL) without any lubricant (P < 0.05). I-DROP PUR GEL, OASIS TEARS PLUS, I-DROP MGD, REFRESH OPTIVE ADVANCED, and OPTASE INTENSE had the highest NIKBUT using this eye model.

Conclusions: The results show that the viscosity is correlated with NIKBUT, but further work is necessary to determine the underlying mechanisms.

Ramaswamy,M., Ho,B., Phan,C. M., Qin,N., Ren,C. L., Jones,L. Inexpensive and rapid fabrication of PDMS microfluidic devices for biological testing applications using low cost commercially available 3D printers Journal of Micromechanics and Microengineering 2023;Online ahead of print [ Show Abstract ]

Polydimethylsiloxane (PDMS) elastomers have been extensively used in the development of microfluidic devices, capable of miniaturizing biomolecular and cellular assays to the microliter and nanoliter range, thereby increasing the throughput of experimentation. PDMS has been widely used due to its optical clarity and biocompatibility, among other desirable physical and chemical properties. Despite the widespread use of PDMS in microfluidic devices, the fabrication process typically requires specialized facilities, instruments, and materials only available in a limited number of laboratories. To expand microfluidic research capabilities to a greater scientific population, we developed and characterized a simple and robust method of fabricating relatively inexpensive PDMS microfluidic devices using readily available reagents and commercially available 3D printers. The moulds produced from the 3D printers resolve designed microfluidic channel features accurately with high resolution ( >100 µm). The critical physical and chemical post-processing modifications we outline here are required to generate functional and optically clear microfluidic devices.

Schulze,M., Fadel,D., Luensmann,D., Ng,A. Y., Guthrie,S., Woods,J., Jones,L. Evaluating the Performance of verofilcon A Daily Disposable Contact Lenses in a Group of Heavy Digital Device Users Clinical Ophthalmology 2023;173165-3175 [ Show Abstract ]

Purpose: The purpose of this study was to evaluate the performance of verofilcon A daily disposable contact lenses (CL) in CL wearers who identified themselves as heavy digital device users.
Patients and Methods: This prospective, non-masked, open-label study enrolled CL wearers who reported ≥ 6 hours digital device use per day. Participants were dispensed with the verofilcon A study lenses for 14± 2 days, to be worn for at least 5 days a week and 10 hours per day, while continuing their normal routine of digital device use. Participants rated the lens performance at the Day 14 visit using a 0– 100 (with 100 being best) scale. Ratings were completed at lens insertion, after 6 hours of digital device use, just before CL removal and for overall experience. Participants also completed a 4-point (strongly agree/disagree, slightly agree/disagree) Likert scale-based questionnaire.
Results: Thirty-two participants were eligible and completed the study (27 females; age 25.8 ± 6.0 years, ranging from 19 to 40). Overall lens performance ratings at the Day 14 visit (mean ± standard deviation) for comfort, dryness, and clarity of vision were 91 ± 11, 88 ± 11, and 92 ± 9, respectively. Subjective ratings were stable throughout the day with no significant differences after insertion, after 6 hours of digital device use and before CL removal (all p> 0.05). The majority of participants agreed that the study lenses performed well, provided good all-day comfort (28/32; p< 0.01) and good all-day vision (29/32; p< 0.01). Participants also agreed that after ≥ 6 hours of digital device use they were satisfied with CL comfort (27/32; p< 0.01), vision (29/32; p< 0.01) and that the lenses provided good performance (26/32; p< 0.01).
Conclusion: Verofilcon A lenses were found to perform well, with high ratings for comfort, dryness and vision that remained high throughout the day, during extensive digital device use.

Spafford,M. M., Chow,A. H. Y., Labreche,T., Jones,D. A., Christian,L. W. T., Furtado,N. M., MacIver,S., Irving,E. L. Trust and Access: Eye Information-seeking Practices and Preferences among Canadians Optometry and Vision Science 2023;100(7):467-474 [ Show Abstract ]

SIGNIFICANCE
This study highlights the value that the public places on obtaining trusted and accessible health-related information and their preference for obtaining it from their health care practitioners. Previous research has not been specific to Canadians or vision. Findings can be used to increase eye health literacy and eye care utilization.

PURPOSE
Canadians underuse eye care and underestimate the occurrence of asymptomatic eye disease. This study explored eye information-seeking practices and preferences among a group of Canadians.

METHODS
Using snowball sampling, a 28-item online survey collected respondent perceptions about their eye and health information-seeking practices and preferences. Questions examined electronic device access, information source use, and demographics. Two open-ended questions examined information-seeking practices and preferences. Respondents were at least 18 years old and living in Canada. Individuals working in eye care were excluded. Response frequencies and z scores were computed. Written comments were assessed using content analysis.

RESULTS
Respondents searched for less eye than health information (z scores ≥ 2.25, P < .05). For eye and health information, primary care providers were the used and preferred source, and reliance on Internet searches was greater than desired. Trust and access drove information-seeking practices. Respondent comments suggested that a hierarchy of trust operates across My Health Team, My Network, and My External Sources, with a persistent threat posed by Discredited Sources. Access to information sources seemed mediated by enablers (Convenience and Accessible Features) and barriers (Unreachable Health Team and Absent Systems). Eye information was seen as more specialized and harder to find. There was a high regard for health care practitioners who provide their patients with curated trusted information.

CONCLUSIONS
These Canadians value trusted and accessible health-related information. They prefer eye and health information from their health care practitioners and value when their health team provides online curated information, particularly regarding eyes.

Stapleton,F., Abad,J. C., Barabino,S., Burnett,A., Iyer,G., Lekhanont,K., Li,T., Liu,Y., Navas,A., Obinwanne,C. J., Qureshi,R., Roshandel,D., Sahin,A., Shih,K., Tichenor,A., Jones,L. TFOS Lifestyle: Impact of societal challenges on the ocular surface Ocular Surface 2023;28(April):165-199 [ Show Abstract ]

Societal factors associated with ocular surface diseases were mapped using a framework to characterize the relationship between the individual, their health and environment. The impact of the COVID-19 pandemic and mitigating factors on ocular surface diseases were considered in a systematic review. Age and sex effects were generally well-characterized for inflammatory, infectious, autoimmune and trauma-related conditions. Sex and gender, through biological, socio-economic, and cultural factors impact the prevalence and severity of disease, access to, and use of, care. Genetic factors, race, smoking and co-morbidities are generally well characterized, with interdependencies with geographical, employment and socioeconomic factors. Living and working conditions include employment, education, water and sanitation, poverty and socioeconomic class. Employment type and hobbies are associated with eye trauma and burns. Regional, global socio-economic, cultural and environmental conditions, include remoteness, geography, seasonality, availability of and access to services. Violence associated with war, acid attacks and domestic violence are associated with traumatic injuries. The impacts of conflict, pandemic and climate are exacerbated by decreased food security, access to health services and workers. Digital technology can impact diseases through physical and mental health effects and access to health information and services. The COVID-19 pandemic and related mitigating strategies are mostly associated with an increased risk of developing new or worsening existing ocular surface diseases. Societal factors impact the type and severity of ocular surface diseases, although there is considerable interdependence between factors. The overlay of the digital environment, natural disasters, conflict and the pandemic have modified access to services in some regions.

Sullivan,D., da Costa,A. X., Del Duca,E., Doll,T., Grupcheva,C. N., Lazreg,S., Liu,S-H., McGee,S. R., Murthy,R., Narang,P., Ng,A. Y., Nistico,S., O'Dell,L., Roos,J., Shen,J., Markoulli,M. TFOS lifestyle: Impact of cosmetics on the ocular surface Ocular Surface 2023;29(July):77-130 [ Show Abstract ]

In this report the use of eye cosmetic products and procedures and how this represents a lifestyle challenge that may exacerbate or promote the development of ocular surface and adnexal disease is discussed. Multiple aspects of eye cosmetics are addressed, including their history and market value, psychological and social impacts, possible problems associated with cosmetic ingredients, products, and procedures, and regulations for eye cosmetic use. In addition, a systematic review that critically appraises randomized controlled trial evidence concerning the ocular effects of eyelash growth products is included. The findings of this systematic review highlight the evidence gaps and indicate future directions for research to focus on ocular surface outcomes associated with eyelash growth products.

Watson,S. L., Jones,L. W., Stapleton,F., Hinds,M., Ng,A.Y., Tan,J, Alster,Y., Bosworth,C., Rafaeli,O., DePuy,V, Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: A vehicle-controlled, randomized clinical trial The Ocular Surface 2023;29(July):537-546 [ Show Abstract ]

Purpose
Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD.

Methods
A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs).

Results
AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug).

Conclusions
Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated.

Wong,K. Y., Phan,C.M., Chan,Y.T., Chuy-Ying Yuen,A., Zhao,D., Chan,K. Y., Do,C. W., Chuen Lam,T., Han Qiao,J., Wulff,D., Hui,A., Jones,L., Wong,M. S. A review of using Traditional Chinese Medicine in the management of glaucoma and cataract Clinical and Experimental Optometry 2023;Online ahead of print [ Show Abstract ]

Traditional Chinese Medicine has a long history in ophthalmology in China. Over 250 kinds of Traditional Chinese Medicine have been recorded in ancient books for the management of eye diseases, which may provide an alternative or supplement to current ocular therapies. However, the core holistic philosophy of Traditional Chinese Medicine that makes it attractive can also hinder its understanding from a scientific perspective – in particular, determining true cause and effect. This review focused on how Traditional Chinese Medicine could be applied to two prevalent ocular diseases, glaucoma, and cataract. The literature on preclinical and clinical studies in both English and Chinese on the use of Traditional Chinese Medicine to treat these two diseases was reviewed. The pharmacological effects, safety profile, and drug-herb interaction of selected herbal formulas were also investigated. Finally, key considerations for conducting future Traditional Chinese Medicine studies are discussed.

Woods,C., Naroo,S., Zeri,F., Bakkar,M., Barodawala,F., Evans,V., Fadel,D., Kalikivayi,L., Lira,M., Maseedupally,V., Trave Huarte,S., Eperjesi,F. Evidence for commonly used teaching, learning and assessment methods in contact lens clinical skills education Contact Lens Anterior Eye 2023;46(2):101821 [ Show Abstract ]

Introduction
Evidence based practice is now an important part of healthcare education. The aim of this narrative literature review was to determine what evidence exists on the efficacy of commonly used teaching and learning and assessment methods in the realm of contact lens skills education (CLE) in order to provide insights into best practice. A summary of the global regulation and provision of postgraduate learning and continuing professional development in CLE is included.

Method
An expert panel of educators was recruited and completed a literature review of current evidence of teaching and learning and assessment methods in healthcare training, with an emphasis on health care, general optometry and CLE.

Results
No direct evidence of benefit of teaching and learning and assessment methods in CLE were found. There was evidence for the benefit of some teaching and learning and assessment methods in other disciplines that could be transferable to CLE and could help students meet the intended learning outcomes. There was evidence that the following teaching and learning methods helped health-care and general optometry students meet the intended learning outcomes; clinical teaching and learning, flipped classrooms, clinical skills videos and clerkships. For assessment these methods were; essays, case presentations, objective structured clinical examinations, self-assessment and formative assessment. There was no evidence that the following teaching and learning methods helped health-care and general optometry students meet the intended learning outcomes; journal clubs and case discussions. Nor was any evidence found for the following assessment methods; multiple-choice questions, oral examinations, objective structured practical examinations, holistic assessment, and summative assessment.

Conclusion
Investigation into the efficacy of common teaching and learning and assessment methods in CLE are required and would be beneficial for the entire community of contact lens educators, and other disciplines that wish to adapt this approach of evidence-based teaching.

Yamasaki,K., Dantam,J., Sasanuma,K., Hisamura,R., Mizuno,Y., Hui,A., Jones,L. Impact of in vitro lens deposition and removal on bacterial adhesion to orthokeratology contact lenses Contact Lens Anterior Eye 2023;Online ahead of print [ Show Abstract ]

Purpose
The purpose of this study was to explore the impact of several contact lens (CL) care solutions on the removal of proteins and lipids, and how deposit removal impacts bacterial adhesion and solution disinfection.

Methods
Lysozyme and lipid deposition on three ortho-k (rigid) and two soft CL materials were evaluated using an ELISA kit and gas chromatography respectively. Bacterial adhesion to a fluorosilicone acrylate material using Pseudomonas aeruginosa with various compositions of artificial tear solutions (ATS), including with denatured proteins, was also investigated. The impact of deposition of the different formulations of ATS on biofilm formation was explored using cover slips. Finally, the lysozyme and lipid cleaning efficacy and disinfection efficacy against P. aeruginosa and Staphylococcus aureus of four different contact lens care solutions were studied using qualitative analysis.

Results
While maximum lysozyme deposition was observed with the fluorosilicone acrylate material (327.25 ± 54.25 µg/lens), the highest amount of lipid deposition was recorded with a fluoro-siloxanyl styrene material (134.71 ± 19.87 µg/lens). Adhesion of P. aeruginosa to fluorosilicone acrylate lenses and biofilm formation on cover slips were significantly greater with the addition of denatured proteins and lipids. Of the four contact lens care solutions investigated, the solution based on povidone-iodine removed both denatured lysozyme and lipid deposits and could effectively disinfect against P. aeruginosa and S. aureus when contaminated with denatured proteins and lipids. In contrast, the peroxide-based solution was able to inhibit P. aeruginosa growth only, while the two multipurpose solutions were unable to disinfect lenses contaminated with denatured proteins and lipids.

Conclusion
Bacterial adhesion and biofilm formation is influenced by components within artificial tear solutions depositing on lenses, including denatured proteins and lipids, which also affects disinfection. The ability of different solutions to remove these deposits should be considered when selecting systems to clean and disinfect ortho-k lenses.

Zaidi,A., Seo,J., McCanna,D.J., Mahil,A., Jones,L. Molecular biology of two common ophthalmic viruses: Relevance to clinical practice Optometry in Practice 2023;24(1): [ Show Abstract ]

Due to the coronavirus pandemic, viruses have suddenly become a prominent topic of discussion. As such, it
is important to understand the life cycle and, ultimately, the process of inactivating viruses. To inactivate them
it is important to block the mechanisms that they use to induce infection. Due to their ability to survive on
various surfaces, appropriate cleaning practices to prevent viral spread and contamination of medical devices,
practice equipment and surfaces are paramount. Depending on the type of virus and genome configurations,
various mechanisms are used to induce a viral infection. Understanding the susceptibility of the viral outer
coating is crucial to preventing viral spread, whether through droplet transmission or while on surfaces (fomite
transmission). Knowledge of how viral receptors and proteins interact to facilitate the recognition, attachment
and entry of a virus into the host cell is vital for an understanding of how disinfectants and antivirals can be
effective. Viral replication, transcription and translation are also major targets of antivirals. This paper will
review the physiology of two major ophthalmic viruses: adenovirus and herpes simplex.

2022

Bzovey,B., Ngo,W. Eyelid Warming Devices: Safety, Efficacy, and Place in Therapy Clinical Optometry 2022;14133-147 [ Show Abstract ]

Meibomian gland dysfunction (MGD) is characterized by the obstruction and/or inflammation of the meibomian glands that result in decreased and altered meibum secretion. This results in deficiencies in the tear film lipid layer which contributes to increased evaporation and destabilization of the tear film. One of the mainstay therapies for MGD is medical devices that apply heat and/or pressure to the eyelids and promote the liquification and outflow of meibum into the tear film. Over the past two decades, there have been a surge of interest in diagnosing and managing MGD. As a result, numerous medical devices have been developed and each have their own unique approach to treating MGD. This narrative review was conducted to summarize the current state of knowledge on eyelid warming devices, specifically warm eye coverings, devices that direct heat and/or pressure to the eyelids, moisture chamber goggles, and light-based therapy. This review summarized 58 human clinical studies and found that most eyelid warming devices were efficacious in improving signs and symptoms in a wide range of MGD severities and were generally safe to use.

Chamberlain,P., Bradley,A., Arumugam,B., Hammond,D., McNally,J., Logan N., Jones,D., Ngo,C., Peixoto-de-Matos S., Hunt,C., Young G. Long-term Effect of Dual-focus Contact Lenses on Myopia Progression in Children: A 6-year Multicenter Clinical Trial Optom Vis Sci 2022;99(3):204-212 [ Show Abstract ]

Significance: Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a six-year period. Significant slowing was also observed in children switched from control to treatment lenses (3 years in each lens).

Purpose: Evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period. Assess myopia progression in children who were switched to DFCL at the end of year 3.

Methods: Part 1 was a 3-year clinical trial comparing DFCLs with control CLs (Proclear 1 day) at four investigational sites. In Part 2, subjects completing Part 1 were invited to continue for 3 additional years during which all children were treated with MiSight 1 day DFCLs (52 and 56 from the initially treated (T6) and control (T3) groups, respectively). 85 subjects (45 (T3) and 40 (T6)) completed Part 2. Cyclopleged spherical equivalent refractive errors (SERE) and axial lengths (AL) were monitored and linear mixed model was used to compare their adjusted change annually.

Results: Average age at Part 2 baseline was 13.2 ± 1.3 and 13.0 ± 1.5 for the T6 & T3 groups respectively. Slowed myopia progression in the T6 group observed during Part 1 was sustained throughout Part 2 (Mean ± SEM: Change from baseline SERE(D) = -0.52 ± 0.076 vs -0.51 ± 0.076; change in AL(mm) = 0.28 ± 0.033 vs 0.23 ± 0.033, both P > .05). Comparing progression rates in Part 2 for the T6 and T3 groups respectively indicate that prior treatment does not influence efficacy (SERE -0.51 ± 0.076 vs -0.34 ± 0.077; AL 0.23 ± 0.03 vs 0.18 ± 0.03, both P > .05). Within-eye comparisons of AL growth revealed a 71% slowing for the T3 group (3-years older than Part 1), and further revealed a small subset of eyes (10%) that did not respond to treatment.

Conclusions: DFCLs continue to slow the progression of myopia in children over a six-year period revealing an accumulation of treatment effect. Eye growth of the initial control cohort with DFCL was slowed by 71% over the subsequent 3-year treatment period.

Craig,J. P., Bitton,E., Dantam,J., Jones,L., Ngo,W., Wang,M. T. M Short-term tolerability of commercial eyelid cleansers: A randomised crossover study Contact Lens Anterior Eye 2022;45(6):101733 [ Show Abstract ]

Purpose
To evaluate the short-term tolerability of five commercially available anti-demodectic eyelid cleansers; OCuSOFT Oust Demodex (OD), I-MED I-Lid’n Lash Plus (ILL+), Labtician BlephaDex (BD), Chrissanthe Eye Cleanse (EC), and Théa Blephademodex (BDdx).

Methods
Thirty healthy non-contact lens wearers (18 female; mean ± SD age, 33 ± 12 years) were enrolled in a prospective randomised crossover study. On separate visits, spaced at least 48 h apart, participants were randomised to receive topical application of one of five eyelid cleansers or saline. Participants rated subjective ocular discomfort during the 10-minute post-application period. Visual acuity, non-invasive tear film stability, conjunctival hyperaemia, and ocular surface staining were assessed at baseline and 10 min.

Results
No inter-group differences in ocular parameters were noted at baseline (all p > 0.05). Ocular discomfort scores significantly exceeded baseline scores for 60 s following BD application, 120 s with OD, 135 s with BDdx, 150 s with ILL+, and 195 s with EC (all p < 0.05). Deterioration in non-invasive tear film stability, limbal conjunctival hyperaemia, as well as corneal, conjunctival, and lid margin staining was detected following EC application (all p < 0.05), and increased bulbar conjunctival hyperaemia was observed following both EC and ILL+ treatment (both p < 0.05).

Conclusions
Study outcomes highlight varying tolerability profiles with different anti-demodectic lid cleanser preparations, and the potential to induce tear film instability, conjunctival hyperaemia and ocular surface staining on application. Awareness of possible adverse effects arising from topical application of commercial anti-demodectic lid cleanser formulations may help clinicians set realistic patient expectations and encourage better compliance in their use of lid hygiene therapies.

Dare,E. V., Fung,C. K., McCanna,D. J., Subbaraman, L. V., Jones,L. W. Establishment of optimal culture media in corneal epithelial wound healing models Journal of Cellular Biotechnology 2022;8(1):1-12 [ Show Abstract ]

BACKGROUND: Wound healing needs to occur after injury to prevent vision loss. Models of wound healing need to be optimized to assure treatments for corneal wounds can be developed in vitro prior to investigating with in vivo studies.

OBJECTIVE: The purpose of this study was to establish the optimum media to use as a control solution in wound healing models.

METHODS: Immortalized human corneal epithelial cells were cultured in different growth media using a scratch and exclusion zone model. The effect of normoxic and hypoxic conditions on tight junctional integrity and metabolic activity of cells grown in different growth medium were also investigated.

RESULTS: Wound healing with DMEMF12 media was significantly faster than both Keratinocyte serum-free media (p < 0.05) and EpiLife (p < 0.05) after 10 hours recovery under normoxic or hypoxic conditions using the scratch model and 9 days after wounding using the exclusion zone technique (p < 0.05). Using the culture media DMEMF12, cells stained for abundant ZO-1, Cx43 and had a high metabolic activity indicating significant epithelial barrier formation, gap junction formation and high cell viability.

CONCLUSIONS: DMEMF12 led to superior wound healing under hypoxic and normoxic conditions and in two different wound healing models. © 2022-IOS Press. All rights reserved.

Desai,D. T., Maulvi,F. A., Desai,A. R., Shukla,M. R., Desai,B. V., Khadela,A. D., Shetty,K. H., Shah,D. O., Willcox,M. D. P. In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses International Journal of Pharmaceutics 2022;613121414 [ Show Abstract ]

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

Efron,N., Jones,L. W., Morgan,P. B., Nichols,J. J. Bibliometric analysis of the literature relating to silicone hydrogel and daily disposable contact lenses Journal of Optometry 2022;15(1):44-52 [ Show Abstract ]

Purpose
Publication metrics are derived for the fields of silicone hydrogel (SH) and daily disposable (DD) contact lenses.

Methods
A search of the Scopus database for papers in the fields of SH and DD contact lenses found 979 SH and 291 DD papers. Subject-specific h-indices for SH lenses (hSH-index) and DD lenses (hDD-index) were derived, in relation to five categories – authors, institutions, countries and journals – to serve as measures of impact. A short list of the most impactful entities was generated for each of the above five categories in the SH and DD fields.

Results
A paper entitled “Soft contact lens polymers: An evolution” by Nicholson and Vogt was the most highly cited article (495 citations) in both SH and DD fields. The most impactful entities for the SH and DD fields were: authors – Lyndon Jones (hSH = 33) and Philip Morgan (hDD = 15); institutions – the University of Waterloo (hSH = 37) and the University of New South Wales (hDD = 15); countries – the United States (hSH = 45) and the United Kingdom (hDD = 24); and journals – Optometry and Vision Science (hSH = 33) and Contact Lens and Anterior Eye (hDD = 17). Overall, the SH field (hSH = 64) is far more impactful than the DD field (hDD = 34).

Conclusions
Impactful papers, authors, institutions, countries and journals in the SH and DD fields are identified. Optometry is revealed as the leading profession in relation to SH and DD publications.

Efron,N., Morgan,P. B., Nichols,J. J., Walsh,K., Willcox,M. D., Wolffsohn,J. S. Jones,L. W. All soft contact lenses are not created equal Contact Lens Anterior Eye 2022;45(2):Article 101515 [ Show Abstract ]

Abstract
Soft contact lenses that have been prescribed by eye care practitioners are sometimes substituted for alternative lenses by unqualified, unregulated and sometimes even fully regulated lens suppliers, in the mistaken belief that there is essentially no difference between different soft lens types. This review considers the implications of inappropriately substituting soft contact lens types in terms of (a) lens properties: surface treatment, internal wetting agents, material, total diameter, back optic zone radius, thickness, edge profile, back surface design, optical design, power, colour (tint) and ultraviolet protection; and (b) lens usage: wearing modality (daily versus overnight wear) and replacement frequency. Potential aspects of patient dissatisfaction and adverse events when prescribed soft lenses are substituted for lenses with different properties or intended usage are considered. Substitution of 15 of the 16 lens properties considered (i.e. except for back surface design) was found to be related to at least one – and as many as six – potential sources of patient dissatisfaction and adverse ocular events. Contact lens are medical devices which are prescribed and fitted; they should never be substituted for another lens type in the absence of a new prescription further to a full finalised fitting, for the simple reason that all soft contact lenses are not created equal. A substituted lens may have properties that results in undesirable consequences in respect of vision, ocular health, comfort and cosmetic appearance, and may be incompatible with the lifestyle of the patient.

Guthrie,S., Ng,A. Y., Woods,J., Vega,J., Orsborn,G., Jones,L. Exploring the factors which impact overall satisfaction with single vision contact lenses Contact Lens Anterior Eye 2022;45(5):101579 [ Show Abstract ]

Purpose
To explore the impact of subjective factors (lens handling, comfort and vision) on overall single vision contact lens satisfaction.

Methods
Correlation analysis of a prospective, randomised, double-masked, bilateral crossover study involving 55 adapted lens wearers fitted with somofilcon A (SiHy) (clariti® 1 day, CooperVision) and etafilcon A (Hy) (1 DAY ACUVUE® MOIST, Johnson & Johnson Vision) was conducted. Subjective ratings of lens handling, comfort and vision collected after 1 week of lens wear for each lens type were correlated with overall satisfaction. Data were analysed by combining data for both lens types and also for each lens separately.

Results
For the combined analysis, significant correlations (p < 0.01) were found between subjective ratings of overall satisfaction and ratings of handing for application (r = 0.64), handling for removal (r = 0.50), comfort upon application (r = 0.59), comfort at end of day (r = 0.61), overall satisfaction with comfort (r = 0.88) and overall satisfaction with vision (r = 0.64).

Correlation analysis of the per lens data showed that lens specific correlations of overall satisfaction with handling for lens application varied greatly with lens material (SiHy: r = 0.26, p = 0.05 vs Hy: r = 0.72, p < 0.01). Correlation strength of comfort upon application/at end of day with overall satisfaction also varied with lens material (Application: SiHy: r = 0.40 vs Hy: r = 0.61; End of day: SiHy: r = 0.76 vs Hy: r = 0.58; all p ≤ 0.01).

Conclusion
Overall satisfaction was significantly correlated with the specific subjective evaluations of handling, vision and comfort. Correlations of overall satisfaction and ease of handling for each lens type suggest that, for habitual contact lens wearers, dissatisfaction with handling at the time of lens application can play a major role in overall dissatisfaction with a lens. Handling for application had a similar correlation (r) value as vision, suggesting that handling for application should not be underestimated when considering overall patient satisfaction.

Kao,E. C. Y., Seo,J., McCanna,D. J., Subbaraman,L. N., Jones,L. In vitro assessment of the biocompatibility of chemically treated silicone materials with human lens epithelial cells Nature - Scientific Reports 2022;12(1):Article 4649 [ Show Abstract ]

Cytotoxicity testing is a regulatory requirement for safety testing of new ocular implants. In vitro toxicity tests determine whether toxic chemicals are present on a material surface or leach out of the material matrix. A method of evaluating the cytotoxicity of ocular implants was developed using fluorescent viability dyes. To assess the assay’s sensitivity in detecting toxic substances on biomaterials, zinc diethydithiocarbamate (ZDEC) and benzalkonium chloride (BAK) were deposited on silicone surfaces at different concentrations. Human lens epithelial cells (HLEC) were added to the surface of these treated silicone surfaces and were assessed for viability. The viability of both the adherent and non-adherent cells was determined using confocal microscopy with, annexin V, ethidium homodimer, and calcein. Cell metabolism was also evaluated using resazurin and the release of inflammatory cytokines was quantified using a multiplex Mesoscale Discovery platform. Confocal microscopy was shown to be a sensitive assay for evaluating material toxicity, as significant toxicity (p < 0.05) from ZDEC and BAK-treated surfaces compared to the untreated silicone control was detected. Patterns of cytokine release from cells varied depending on the toxin evaluated and the toxin concentration and did not directly correlate with the reduction in cell metabolic activity measured by alamarBlue.

Kapadia,W., Qin,N., Zhao,P., Phan,C.-M., Haines,L., Jones,L. Ren,C. L. Shear-Thinning and Temperature-Dependent Viscosity Relationships of Contemporary Ocular Lubricants Translational Vision Science & Technology 2022;11(3):Article 1 [ Show Abstract ]

Purpose: To evaluate the shear viscosity of contemporary, commercially available ocular lubricants at various shear rates and temperatures and to derive relevant mathematical
viscosity models that are impactful for prescribing and developing eye drops to treat dry eye disease.

Methods: The shear viscosity of 12 ocular lubricants was measured using a rheometer and a temperature-controlled bath at clinically relevant temperatures at which users may experience exposure to the drops (out of the refrigerator [4.3°C]; room temperature [24.6°C]; ocular surface temperature [34.5°C]). Three replicates for each sample at each temperature were obtained using a standard volume (0.5 mL) of each sample. The viscosity of each ocular lubricant was measured over the full range of shear rates allowed
by the rheometer.

Results: The shear viscosity of the same ocular lubricant varied significantly among the three temperatures. In general, a higher temperature resulted in smaller viscosities than a lower temperature (an average of −48% relative change from 4.3°C to 24.6°C and −21% from 24.6°C to 34.5°C). At a constant temperature, the viscosity of an ocular lubricant over the studied shear rates can be well approximated by a power-law model.

Conclusions: Rheological analysis revealed that the ocular lubricants exhibited shear-thinning behavior at the measured temperatures. Differences in the ocular lubricants’ formulations and measured temperatures resulted in different viscosities.

Translational Relevance: When prescribing eye drops, eye care professionals can select the optimal one for their patients by considering a variety of factors, including its
rheological property at physiologically relevant shear rates and temperatures, which can improve residence time on the ocular surface, while ensuring appropriate comfort and vision. However, care must be taken when using the derived mathematical models in this study because the in vivo shear behavior of the ocular lubricants has not been examined and might show deviations from those reported when placed on the ocular surface.

Khanal,S., Bai,Y., Ngo,W., Nichols,K. K., Wilson,L., Barnes,S., Nichols,J. J. Human meibum and tear film derived cholesteryl and wax esters in meibomian gland dysfunction and tear film structure: Cholesteryl and wax esters in meibomian gland dysfunction Ocular Surface 2022;23(January):12-23 [ Show Abstract ]

Purpose
This study evaluated the presence and roles of cholesteryl esters (CEs) and wax esters (WEs) from human tear film and meibum in meibomian gland dysfunction (MGD).

Methods
Out of 195 enrolled subjects, 164 and 179 subjects provided tear and meibum samples, respectively. Subjects were classified into normal, asymptomatic MGD, MGD, and mixed (MGD & aqueous deficient). The precorneal tear film (PCTF) thinning rate (evaporation) was measured using optical coherence tomography. Lipids extracted from tear and meibum samples were infused into a SCIEX 5600 TripleTOF mass spectrometer. CE and WE intensities quantified with Analyst 1.7 TF and LipidView 1.3 were compared across disease groups in MetaboAnalyst 5.0 and correlated with PCTF thinning rates.

Results
The numbers of unique CEs and WEs identified in the samples were 125 and 86, respectively. Unsupervised Principal Component (PC) analysis and supervised Partial Least Square Discriminant analysis exhibited little separation among groups for both CEs and WEs in tears and meibum. Spearman's correlation analyses showed no association between either the first or second PC scores with PCTF thinning rates.

Conclusion
The abundances of human PCTF and meibum-derived CEs and WEs were independent of MGD disease status and PCTF thinning (evaporation). CEs and WEs alterations do not contribute to alterations in tear film dynamics in MGD, such as has been demonstrated by the (O-acyl) ω-hydroxy fatty acids (OAHFAs).

Leat,S. J., Saraf,A., Rose,K., Christian,L. W., Irving,E. L., Jones, D. A., McCulloch, D. L. Measuring recognition visual acuity in young children–testability with the Waterloo Differential Acuity Test (WatDAT) Clinical and Experimental Optometry 2022;Online ahead of print [ Show Abstract ]

Clinical relevance: Visual acuity measurement is important for the detection and monitoring of eye disorders. Developing accurate and sensitive visual acuity tests suitable for young children is therefore desirable.

Background: Recognition or form visual acuity (VA), which is measured with matching in children aged 3 years and up, is more sensitive for detecting visual deficits compared to resolution VA. The Waterloo Differential Acuity Test (WatDAT) is a proposed recognition VA test using the concept of identifying the "odd one out" among distractors. The WatDAT is expected to be cognitively easier than matching tests and therefore may be used in younger children. The purpose of this study is to investigate the testability of the WatDAT paradigm in children aged 12-36 months, and to determine the optimum format and number of distractors.

Methods: Fifty-one typically-developing children aged 12-36 months participated in the study. Data for Patti Pics (PP) and Face targets (FT) were collected for formats with 3, 4 and 5 distractors. The targets were presented binocularly on a computer touch screen at 30 cm. The task was to touch the face among identical non-faces or a house among circles. Following initial training, there were 5 presentations for each distractor format. Testability was defined as correctly identifying at least 4/5 presentations and was also determined for uncrowded PP symbols using matching.

Results: Of participants aged 18-36 months, 87% could perform the WatDAT PP targets with 3 distractors compared to 68% for the FT, while 48% could perform matching with PP. The testability for FT increased to 85% for children ≥22 months. Younger children showed lower testability. For the 3 distractor format, PP targets gave 9% testability in children 12 to <18 months, and FT gave a testability of 16% in children 12 to <22 months.

Conclusion: WatDAT testability is higher than matching VA tests. This indicates that the newly developed WatDAT has potential for measuring recognition VA in children 18 months and older.

Lourenco Nogueira,C., Boegel,S. C., Shukla,M., Ngo,W., Jones,L., Aucoin,M. G. Antiviral Activity of Contemporary Contact Lens Care Solutions against Two Human Seasonal Coronavirus Strains Pathogens 2022;11(4):472 [ Show Abstract ]

Background: Given that reports have suggested SARS-CoV-2 can be transmitted via conjunctiva, the ability of contact lens (CL) care products to reduce the infectiousness of two seasonal human coronavirus (HCoV) (HCoV-229E and HCoV-OC43) surrogates for SARS-CoV-2 was investigated.

Methods: Biotrue and Boston Simplus (Bausch&Lomb), OPTI-FREE Puremoist and Clear Care (Alcon), and cleadew and cleadew GP (Ophtecs) were tested. Their ability to inactivate HCoV was evaluated using contact times of 4 and 6 h as well as 1% and 10% of virus inoculum.

Results: Non-oxidative systems (Biotrue, Boston Simplus, and OPTI-FREE) did not exhibit a significant log10 reduction compared to controls for the two viral strains for either incubation time (all p > 0.05) when 10% tests were performed. For the 1% test, while Boston Simplus and OPTI-FREE exhibited a significant log10 reduction of both HCoV-229E (after 6 h) and HCoV-OC43 (after either 4 or 6 h incubation), those products showed less than 1 log10 reduction of the two infectious viruses. Oxidative systems based on hydrogen peroxide or povidone-iodine showed a significant log10 reduction compared with the controls for both HCoV-229E and HCoV-OC43 in all tested conditions (all p < 0.01). Clear Care led to virus inactivation to below the limit of quantification for tests performed with 1% of inoculum after 6 h incubation, while cleadew and cleadew GP led to inactivation of the two viruses to below the limit of quantification in all tested conditions.

Conclusion: Oxidative CL disinfection systems showed significant virucidal activity against HCoV-229E and HCoV-OC43, while non-oxidative systems showed minimal ability to inactivate the HCoV species examined.

Lourenco Nogueira,C., Boegel,S. C., Shukla,M., Ngo,W., Jones,L. Aucoin,M. G. The impact of a rub and rinse regimen on removal of human coronaviruses from contemporary contact lens materials Contact Lens Anterior Eye 2022;45(6):101719 [ Show Abstract ]

Purpose
To assess the influence of contemporary contact lens (CL) materials on human coronavirus attachment and the influence of a rub and rinse step to remove these viruses.

Methods
The binding rates of HCoV-229E and HCoV-OC43 to eight soft CL materials and four rigid gas permeable materials were analyzed. The impact of a rub and rinse step to remove these viruses from all materials was examined. The efficacy of Biotrue (Bausch & Lomb), OPTI-FREE Puremoist (Alcon), Clear Care (Alcon) and cleadew (Ophtecs) to remove virus contamination from two representative soft lens materials (etafilcon A and lotrafilcon B) was also determined.

Results
Approximately 102 to 103 infectious viral particles were recovered from each CL material. Although some materials were more prone to coronavirus adhesion, contamination of both viral types was reduced to below the limit of quantification (LQ) from all materials using a simple saline rinse step. Exposure to Clear Care and cleadew reduced the number of infectious viral particles from both etafilcon A and lotrafilcon B to below the LQ, while for Biotrue and OPTI-FREE Puremoist, infectious viral particles were reduced to below the LQ only when additional rub and rinse steps were included.

Conclusion
Human coronavirus contamination can be easily removed from CL surfaces. Although CL care products containing hydrogen peroxide and povidone-iodine efficiently removed virus contamination from CL surfaces without the need for a rub and rinse step, a full regimen including rub and rinse steps is crucial when using CL care products based on non-oxidative systems.

Luensmann,D., Schaeffer,J. L., Rumney,N. J., Stanberry,A., Fonn,D. Magnitude of astigmatism – A comparison between eyes Contact Lens Anterior Eye 2022;45(5):101510 [ Show Abstract ]

Purpose
Astigmatism is a highly prevalent refractive error and while studies typically focus to describe the axis symmetry between eyes, little is known about the refractive symmetry. Therefore, this study determined the astigmatic power symmetry between eyes in a large clinic population.

Methods
A clinical chart review was conducted at three optometric practices in the United States, the United Kingdom and Canada and subjective refraction data from 88,891 patients 14–70 years of age who presented with at least −0.25DC refractive astigmatism in at least one eye were included in the analysis. Data were obtained at these practices between January 2014 and March 2017. The overall distribution (%) and magnitude (DC) of astigmatism was determined and refractive differences between eyes were identified.

Results
The mean age of the patients was 42.1 ± 15.9 years and included 51,685 (58%) female and 37,206 (42%) male patients. In this data pool of 177,782 eyes, 10.9% required zero astigmatic correction, while 56.2% had astigmatism of −0.25 to −0.75DC. In total 23.9% of patients presented with astigmatism of at least −0.75DC in only one eye, while the other eye had 0 to −0.50DC. Overall, the difference in astigmatism between eyes was less than −0.75DC for 82.1% of astigmatic patients. For patients who presented with astigmatism of −1.00DC in the right eye, 80.8% of them had an astigmatic prescription of −1.00 ± 0.50DC in the left eye. For an astigmatic prescription of −4.00DC in the right eye, only 40.6% of patients exhibited astigmatism of −4.00DC ± 0.50DC in the left eye.

Conclusions
The majority of patients exhibited a difference in astigmatism between eyes of less than −0.75DC, however the refractive cylinder power symmetry was significantly lower in patients with higher refractive astigmatism.

Nagaarudkumaran,N., Mirzapur,P., McCanna,D. J., Ngo,W. Temporal Change in Pro-Inflammatory Cytokine Expression from Immortalized Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress Current Eye Research 2022;47(11):1488-1495 [ Show Abstract ]

Purpose
To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.

Methods
HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD).

Results
Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1β, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark.

Conclusion
Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line.

Ng,A. Y., Woods,J., Jahn,T., Jones,L., Ritter,J. Effect of a novel omega-3 and omega-6 fatty acid supplement on dry eye disease: a 3-month randomized controlled trial Optometry & Vision Science 2022;99(1):67-75 [ Show Abstract ]

SIGNIFICANCE
Supplementing diet with a novel combination of omega-3 and omega-6 fatty acids significantly improved symptoms in extremely symptomatic participants with dry eye disease (DED).

PURPOSE
This study aimed to determine the effect of daily intake of a novel combination of essential fatty acids on signs and symptoms of DED.

METHODS
Participants with moderate to severe DED were enrolled in a prospective, randomized, double-masked parallel group study. Participants ingested either the treatment supplement containing omega-3 and omega-6 fatty acids (1200 mg eicosapentaenoic acid, 300 mg docosahexaenoic acid, 150 mg γ-linoleic acid) or the placebo (coconut and olive oil) daily for 3 months. To determine compliance, Omega-3 Index blood tests were conducted. At baseline and at 1 and 3 months, the following assessments were conducted: Ocular Surface Disease Index (OSDI) questionnaire and Symptom Assessment Questionnaire in Dry Eye, noninvasive tear breakup time, tear meniscus height, tear osmolarity, ocular redness, surface staining, Schirmer test, and meibography.

RESULTS
Fifty participants (mean ± standard deviation baseline OSDI score, 52.2 ± 16.5) completed the study: 24 randomized to treatment and 26 randomized to placebo. Although there was an improvement in OSDI score at 3 months for both groups (treatment: −13.4 points, P = .003; placebo: −7.8 points, P = .02), participants with baseline OSDI scores >52 demonstrated an even larger significant improvement in symptoms with the treatment at 3 months compared with baseline (n = 13, −20.8 points, P = .002). There were no significant changes in any of the ocular assessments at 1 or 3 months (all P > .05). After 3 months, Omega-3 Index increased by 34% in the treatment group (baseline, 5.3 ± 0.8; 3 months, 8.0 ± 2.1; P < .001) and did not change in the placebo group (baseline, 4.8 ± 0.8; 3 months, 4.8 ± 0.6; P = .95).

CONCLUSIONS
Supplementation with eicosapentaenoic acid, docosahexaenoic acid, and γ-linoleic acid resulted in a significant and clinically meaningful improvement of dry eye symptoms in extremely symptomatic participants with DED (OSDI ≥52).

Nichols,J. J., Morgan,P. M., Efron,N, Jones,L. W. Global optometrist research ranking derived from a science-wide author database of standardised citation indicators Clinical and Experimental Optometry 2022;105(1):20-25 [ Show Abstract ]

Clinical relevance
Publications in refereed scientific journals provide a rigorous research base that underpins clinical optometric practice. Leading optometrists who generate this literature can be identified and ranked using standardised citation indicators.

Background
This work seeks to identify and rank all optometrists included in a Science-Wide author database of standardised citation indicators (S-W) and to compare this ranking with the Global Optometrist Top 200 Research Ranking (T200).

Methods
A search was conducted for the names of all optometrists in the T200 who were included in the S-W, which is a world-wide listing of the top 2% of scientists in each of 174 subfield disciplines, ranked according to a composite citation indicator (cns) that excludes self-citations and corrects for multiple authorships and author order.

Results
The names of 66 optometrists are found in the S-W. Of these, 58 are designated as working in the primary sub-field ‘Ophthalmology & Optometry’; this listing, in rank-order of cns, is referred to as the ‘S-W-derived Optometrist Research Ranking’ (S-WORR). Australian optometrist Nathan Efron is ranked #1 in the S-WORR. The number (%) of optometrists in the S-WORR from each country is: the United States – 26 (45%), Australia – 12 (21%), the United Kingdom – 11 (19%), Canada – 5 (9%), Spain – 2 (3%), Hong Kong – 1 (2%) and South Africa – 1 (2%). The universities housing the equal highest number of optometrists in the S-WORR (five each) are the University of California, Berkeley, USA; the University of New South Wales, Australia; and Queensland University of Technology, Australia. There is a moderately strong correlation between T200 and S-WORR rankings (ρ = 0.6017, N = 58, p < 0.0001).

Conclusions
The S-WORR represents an elite cohort of optometrists who ought to be celebrated for their outstanding, leading and impactful contributions to optometric research.

Osae,E. A., Jones,L., Nichols,J. J. The impact of contact lenses on meibomian gland morphology Ocular Surface 2022;24(April):148-155 [ Show Abstract ]

Despite years of experience with contact lenses, controversy remains as to whether contact lenses adversely impact the meibomian glands (MG). This review summarizes the present body of evidence, showing that contact lens wear is associated with alterations in MG morphology (up to 80% higher gland atrophy compared to non-wearers) and qualitative changes in MG secretion. Key factors such as duration of contact lens wear, contact lens type (e.g., soft vs. rigid), edge design, and material modulus of elasticity are discussed in relation to the extent of MG morphological changes, the quality of MG secretion and other ocular surface parameters. Longitudinal studies of sufficient statistical power are needed to better understand how contact lens wear affects the MG, risk factors, and the clinical sequelae of these changes.

Pereira-da-Mota,A. F., Phan,C-M., Concheiro,A., Jones,L., Alvarez-Lorenzo,C. Testing drug release from medicated contact lenses: The missing link to predict in vivo performance Journal of Controlled Release 2022;343(March):672-702 [ Show Abstract ]

Contact lenses (CLs) offer a wide variety of advantages as ocular drug-releasing platforms, but the feasibility of medicated CL development is constrained by numerous scientific, technological, and regulatory challenges. One main difficulty is the setting of release rate specifications for each drug, since at present there are no standardized in vitro release models that can appropriately predict the performance of drug-eluting CLs once placed onto the eye. CL-adapted release tests may provide knowledge on how the drug release pattern should perform in vivo to trigger and maintain the therapeutic effects for both anterior and posterior ocular tissues. Moreover, in vitro release tests are valuable tools for quality assessment during production and to investigate the effect of a change in composition or process variables. This review aims to shed light on biorelevant ways of evaluating in vitro drug release from CLs and the feasibility of establishing in vitro-in vivo correlations (IVIVC) to predict in vivo performance. First, general guidelines and Pharmacopeia release tests for topical ophthalmic formulations as well as in vitro release tests implemented for drug-CLs in the last two decades are analyzed. Then, development of an appropriate method to investigate IVIVC is attempted from the few papers simultaneously reporting in vitro release profiles and either in vivo release or therapeutic response. Finally, key points to be considered for in vitro testing drug release from a medicated CL are suggested to pave the way to the clinical arena.

Rueff,E., Tichenor,A. A., Ngo,W., Pucker,A. D. A review of meibomian gland structure, function, and contact lens wear Contact Lens Anterior Eye 2022;45(5):101560 [ Show Abstract ]

Purpose: To provide a balanced literature review of the studies that have evaluated the effect of contact lenses on meibomian gland (MG) health.

Methods: A PubMed.gov literature search was conducted on or before May 15, 2021. No other time constraints were applied. Search terms included the following: "meibomian gland(s)" plus "contact lens(es)" or "meibography" plus "contact lens(es)". Only full text articles written in English were considered. The reference lists of recovered papers were used to identify articles missed during the primary search. Included articles were required to discuss the impact of contact lenses on MG morphology or function and were graded according to the level of evidence presented.

Results: The literature indicates that contact lenses impact MG function; however, the data are equivocal regarding contact lenses inducing MG structural changes. The literature likewise indicates that the mechanism(s) by which contact lenses impact the MGs are likely multifactorial. Recent data suggests that MGs may have some plasticity. Detected differences between studies likely stem from varied populations evaluated, study designs, and the duration of the evaluation periods.

Conclusions: With this literature review finding conflicting relationships between MG health and contact lens use, future longitudinal studies with standardized clinical MG assessments are needed to determine the true impact of contact lenses on MG health. Until these data are obtained, contact lens wearers should undergo a full MG evaluation, especially because recent data suggest that MG treatments may restore MG structure and function.

Thite,N., Desiato,A., Shinde,L., Wolffsohn,J. S., Naroo,S. A., Santodomingo Rubido,J., Cho,P., Jones,D., Villa-Collar,C., Carrillo,G., Chan,O., Wang,H., Iomdina,E., Tarutta,E., Proskurina,O., Fan,C. S., Zeri,F., Bakkar,M. M., Barodawala,F., Dabral,N., Lafosse,E., Lee,C., Nichols,J. J., Chan, J., Park,K., Nair,V., Van Der Worp,E., Vankudre,G., Maseedupally,V., Bhattarai,Y., Nagzarkar,D., Brauer,P., Gil-Cazorla,R. Differences in Practitioner Experience, Practice Type, and Profession in Attitudes Toward Growing Contact Lens Practice Eye & Contact Lens 2022;48(9):369-376 [ Show Abstract ]

Objective: To investigate eye care practitioners' attitudes and perceptions toward potential interventions that can enhance contact lens (CL) practice across the world, and how this is influenced by their practice setting.

Methods: A self-administered, anonymized survey was constructed in English and then forward and backward translated into six more languages. The survey was distributed online via social media platforms and mailing lists involving reputed international professional bodies.
Results: In total, 2,222 responses from 27 countries with sufficient responses were analyzed (53% females, median age- 37 years). Most of the respondents were optometrists (81.9%) and 47.6% were from stand-alone/independent practices. Median working experience in CL prescribing was 11.0 years (IQR: 18.0, 4-22 years). Over two-third of them declared themselves to be very hopeful (22.9%) or hopeful (45.1%) about the future of their CL practice. Among the potential interventions proposed, continuous update of knowledge and skills and competently managing CL-related complications were rated the most important (median score: 9/10 for each). Practitioners working in national/regional retail chains expressed higher proactivity in recommending CLs (9/10) than those in local chains, hospitals, and universities (for all 8/10, P<0.05). National differences were also identified in eye care practitioner attitudes and perceptions (P<0.05).

Conclusions: The study provided important information to delineate a variety of elements characterizing CL practice across the world. These insights can serve as a basis to design strategies at national and international levels

von Ahrenschildt,A., Hanneberg,L., Robich,M., Jones-Jordan,L., Marx,S., Sickenberger,W., Powell,D., Kwan,J. T., Wong,S., Srinivasan,S., Jones,L., Pucker,A. D. Morphological characteristics of Meibomian Glands and their Influence on Dry Eye disease in contact lens wearers Ocular Surface 2022;24(April):93-99 [ Show Abstract ]

Purpose:
Meibomian glands (MG) are now easily imaged via clinical meibography machines. The purpose of this work was to explore the utility of the known MG morphology metrics for predicting dry eye disease (DED) in contact lens (CL) wearers.

Methods:
Successful and previous CL wearers were recruited. DED was diagnosed if the participant's worst eye had a reduced tear meniscus height (TMH) of <0.2 mm or non-invasive tear break-up time (NITBUT) of [removed]5.0. Meibography was performed and images were subjectively graded by two examiners for the following MG characteristics: distorted, tortuous, hooked, abnormal gap, overlapping, fluffy areas, tadpoling, thinned, thickened, ghost, no extension to lid margin, shortened and dropout (atrophy). DED diagnostic ability of each metric was determined with receiver operating characteristic (ROC) analysis.

Results:
A total of 112 participants were recruited, with 18.8% having DED and 60.7% being female. The only MG morphology metrics that were marginally predictive of DED were thickened upper eyelid MGs (p = 0.046), thickened mean upper plus lower eyelid MGs (p = 0.007), and atrophy of upper eyelid MGs (p = 0.043); however, none of these metrics reached a meaningful area under the curve in ROC analysis (all <0.70).

Conclusion:
While abnormal MG morphology is likely suggestive of DED in CL wearers, none of the MG morphology metrics evaluated alone in this study had clinically meaningful predictive value for detecting DED in this group of current and previous CL wearers.

Walsh,K., Jones,L., Moody,K. Addressing common myths and misconceptions in soft contact lens practice Clinical and Experimental Optometry 2022;105(5):459-473 [ Show Abstract ]

Advances in contact lens technology over the past 50 years since the commercialisation of the first soft lenses in 1971 have been incredible, with significant changes in contact lens materials, frequency of replacement, care systems and lens designs occurring. However, despite the widespread availability of contact lenses, penetration rates for those who need vision correction remain in the low single digits and many practitioners seem to hold on to concepts around the potential value of contact lenses that appear based in the dim and distant past and are certainly no longer valid today. This review addresses 10 common ‘myths and misconceptions’ around soft contact lenses using an evidence-based approach that can hopefully dispel some of these incorrect assumptions.

Wolffsohn,J. S., Dhallu,S., Aujla,M., Laughton,D., Tempany,K., Powell,D., Gifford,K., Gifford,P., Wan,K., Cho,P, Stahl,U., Woods,J. International multi-centre study of potential benefits of ultraviolet radiation protection using contact lenses Contact Lens Anterior Eye 2022;45(6):101593 [ Show Abstract ]

Purpose
To examine the effects of long-term ultraviolet radiation (UVR) blocking wearing contact lenses on ocular surface health, eye focus and macular pigment.

Method
210 pre-presbyopic patients were recruited from Birmingham UK, Brisbane Australia, Hong Kong China, Houston USA and Waterloo Canada (n = 42 at each site). All patients had worn contact lenses for ≥ 5 years, half (test group) of a material incorporating a UVR-blocking filter. Ocular health was assessed using slit-lamp biomicroscopy and UV autofluorescence. Accommodation was measured subjectively with a push-up test and overcoming lens-induced defocus. Objective stimulus response and dynamic measures of the accommodative response were quantified with an open-field aberrometer. Macular pigment optical density (MPOD) was assessed using heterochromatic flicker photometry (MPS II).

Results
The two groups of participants were matched for age, sex, race, body-mass-index, diet, lifestyle, UVR exposure, refractive error and visual acuity. Limbal (p = 0.035), but not bulbar conjunctival redness (p = 0.903) was lower in eyes that had worn UVR-blocking contact lenses compared to controls. The subjective (8.0 ± 3.7D vs 7.3 ± 3.3D; p = 0.125) and objective (F = 1.255, p = 0.285) accommodative response was higher in the test group, but the differences did not reach significance. However, the accommodative latency was shorter in eyes that had worn UVR-blocking contact lenses (p = 0.003). There was no significant different in MPOD with UVR filtration (p = 0.869).

Conclusions
Blocking the transmission of UVR is beneficial in maintaining the eye’s ability to focus, suggesting that presbyopia maybe delayed in long-term UVR-blocking contact lenses wearers. These lenses also provide protection to the critical limbal region.

Yee,A., Phan,C-M., Jones,L. Uptake and release of polyhexamethylene biguanide (PHMB) from hydrogel and silicone hydrogel contact lenses using a radiolabel methodology Contact Lens Anterior Eye 2022;45(5):101575 [ Show Abstract ]

Purpose
The purpose of this study was to evaluate the uptake and release of radiolabelled polyhexamethylene biguanide (PHMB) on reusable daily wear contact lenses (CLs) over 7 days.

Methods
Three silicone hydrogel (SH) contact lens materials (lotrafilcon B, balafilcon A, senofilcon A) and two conventional hydrogel (CH) materials (etafilcon A, omafilcon A) were examined. In experiment 1 (1-day study), CLs were soaked in 2 mL of phosphate buffered solution (PBS) containing radiolabelled 14C PHMB (1 µg/mL) for 8 h. The release kinetics of 14C PHMB from the CLs was measured at t = 0.25, 0.5, 1, 2, 4, 8, and 24 h in fresh 2 mL PBS. In experiment 2 (7-day study), the CLs were soaked in the 14C PHMB (1 µg/mL) solution for 8 h followed by a 16-hour release in 2 mL PBS. The lens cycle was repeated daily for 7 days. After both experiments, the residual amount of PHMB remaining within the lenses was extracted to determine the total uptake of PHMB.

Results
In experiment 1, the total uptake of PHMB for etafilcon A was significantly greater than senofilcon A (p = 0.01). There were no significant differences in total uptake of PHMB between other lens materials (p > 0.05). Etafilcon A released more PHMB compared to all other lens types over a 24-hr period (p < 0.001). In experiment 2, all CL materials continued to sorb more PHMB over time (p < 0.001). By day 7, the amount of PHMB sorbed by etafilcon A was significantly greater than senofilcon A (p = 0.02). After day 2, the CH materials released significantly more PHMB than the SH materials (p < 0.01).

Conclusion
The CL materials continued to sorb PHMB with no signs of saturation after 7 days. All lens materials released a consistent amount of PHMB each day. Radioactive labelling provides a sensitive method of assessing the uptake and release of PHMB from CL materials.

2021

Bai,Y., Ngo,W., Khanal,S., Nichols,K. K., Nichols,J. J. Human precorneal tear film and lipid layer dynamics in meibomian gland dysfunction Ocular Surface 2021;21(July):250-256 [ Show Abstract ]

Purpose: To evaluate the precorneal tear film (PCTF) and lipid layer (TFLL) thicknesses and thinning rates in meibomian gland dysfunction (MGD) using a combined ultra-high-resolution optical coherence tomography (OCT) and thickness dependent fringe (TDF) interferometry system.

Methods: Based on the Tear Film and Ocular Surface Society (TFOS) International Workshop on Meibomian Gland Dysfunction diagnostic algorithm, the Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify subjects into four groups: Normal (OSDI<13 and MGS<10), MGD (OSDI≥13 and MGS≥10), Asymptomatic MGD (OSDI<13 and MGS≥10), and Mixed (OSDI≥13 and MGS<10). The OCT/TDF system was used to capture PCTF and TFLL thicknesses and thinning rates. Kruskal-Wallis was used to compare median PCTF and TFLL thicknesses and thinning rates.

Results: There were 190 subjects categorized into four groups: Normal (n = 63), MGD (n = 51), Asymptomatic MGD (n = 29), and Mixed (n = 47). The PCTF was significantly thinner in the Mixed group (3.3 [1.2]) than in the Normal (p < 0.001), MGD (p < 0.001) and Asymptomatic MGD (p = 0.009) groups. Relative to the Normal (4.5 [4.5] μm/min) and Mixed (5.0 [2.0] μm/min) groups, the rate of PCTF thinning was faster in the MGD (8.1 [3.0] μm/min, both p < 0.001) and Asymptomatic MGD (6.9 [3.1] μm/min, p = 0.009 and p = 0.04, respectively) groups. The correlation between PCTF thinning rate and TFLL thickness was ρ = −0.46, p < 0.001.

Conclusions: Symptomatic and asymptomatic MGD shows rapid PCTF thinning rates (evaporation), while the PCTF thickness was reduced in mixed disease. Thicker lipid layers were associated with slower PCTF thinning.

Chan,V. W. Y., Phan,C-M., Ngo,W., Jones,L. Lysozyme Deposition on Contact Lenses in an In Vitro Blink-Simulation Eye Model Versus a Static Vial Deposition Model Eye & Contact Lens 2021;47(7):388-393 [ Show Abstract ]

Purpose:
To evaluate active lysozyme deposition on daily disposable (DD) contact lenses (CL) using a novel in vitro blink model.

Methods:
Three conventional hydrogel DD CL materials (etafilcon A, omafilcon A, nelfilcon A) and three silicone hydrogel DD CL materials (delefilcon A, senofilcon A, somofilcon A) were tested. The device blink rate was set to 6 blinks/min with a tear flow rate of 1 μL/min using an artificial tear solution (ATS) containing lysozyme and other typical tear film components. After incubation at 2, 4, or 8 hr, lenses were removed, and lysozyme activity was measured. A separate experiment was conducted with lenses incubated in a static vial containing 480 μL of ATS.

Results:
Etafilcon A deposited significantly higher amounts of active lysozyme (402±102 μg/lens) than other lens materials after 8 hr (P<0.0001). Etafilcon A had a higher amount of active lysozyme using the blink model compared with the static vial (P=0.0435), whereas somofilcon A (P=0.0076) and senofilcon A (P=0.0019) had a higher amount of lysozyme activity in the vial compared with the blink model.

Conclusion:
The blink model can be tuned to provide quantitative data that closely mimics ex vivo studies and can be used to model deposition of lysozyme on CL materials.

Chan,V. W. Y., Phan,C-M., Walther,H., Ngo,W., Jones,L. Effects of Temperature and Blinking on Contact Lens Dehydration of Contemporary Soft Lens Materials Using an In Vitro Blink Model Translational Vision Science & Technology 2021;10(8):11 [ Show Abstract ]

Purpose: The purpose of this studywas to evaluate the effects of temperature and blinking on contact lens (CL) dehydration using an in vitro blink model.

Methods: Three silicone hydrogel (delefilcon A, senofilcon A, and comfilcon A) and two conventional hydrogel (etafilcon A and omafilcon A) CL materials were evaluated at 1
and 16 hours. The water content (WC) of the CLs was measured using a gravimetric method. Lenses were incubated on a blink model, internally heated to achieve a clinically relevant surface temperature of 35°C. An artificial tear solution (ATS) was delivered to the blink model at 4.5 μL/min with a blink rate of 6 blinks/min. A comparison set of lenses were incubated in a vial containing either 2 mL of ATS or phosphate-buffered saline (PBS) at 35°C.

Results: Increasing temperature to 35°C resulted in a decrease in WC for all tested CLs over time (P ≤ 0.0052). For most CLs, there was no significant difference in WC over time between ATS or PBS in the vial (P > 0.05). With the vial system, WC decreased and plateaued over time. However, on the blink model, for most CLs, the WC significantly decreased after 1 hour but returned toward initial WC levels after 16 hours (P > 0.05).

Conclusions: The reduction in WC of CLs on the eye is likely due to both an increase in temperature and dehydration from air exposure and blinking.

Translational Relevance: This study showed that the novel, heated, in vitro blink model could be used to provide clinical insights into CL dehydration on the eye.

Chang,J. M. L., Seo,J., Kwan,M. M. Y., Oh,S., McCanna,D. J., Subbaraman,L., Jones,L. Determining the Toxicity of UV Radiation and Chemicals on Primary and Immortalized Human Corneal Epithelial Cells Journal of Visualized Experiments 2021;173(July):e62675 [ Show Abstract ]

This article describes the methods of measuring the toxicity of ultraviolet (UV) radiation and ocular toxins on primary (pHCEC) and immortalized (iHCEC) human corneal epithelial cell cultures. Cells were exposed to UV radiation and toxic doses of benzalkonium chloride (BAK), hydrogen peroxide (H2O2), and sodium dodecyl sulfate (SDS). Metabolic activity was measured using a metabolic assay. The release of inflammatory cytokines was measured using a multi-plex interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) assay, and cells were evaluated for viability using fluorescent dyes.

The damaging effects of UV on cell metabolic activity and cytokine release occurred at 5 min of UV exposure for iHCEC and 20 min for pHCEC. Similar percent drops in metabolic activity of the iHCEC and pHCEC occurred after exposure to BAK, H2O2, or SDS, and the most significant changes in cytokine release occurred for IL-6 and IL-8. Microscopy of fluorescently stained iHCEC and pHCEC BAK-exposed cells showed cell death at 0.005% BAK exposure, although the degree of ethidium staining was greater in the iHCECs than pHCECs. Utilizing multiple methods of assessing toxic effects using microscopy, assessments of metabolic activity, and cytokine production, the toxicity of UV radiation and chemical toxins could be determined for both primary and immortalized cell lines.

Craig,J.P., Muntz,A., Wang,M.T.M., Luensmann,D., Tan,J., Travé-Huarte,S., Xue,A.L., Jones,L.W., Willcox,M.D.P., Wolffsohn,J.S. Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial Ocular Surface 2021;20(April):62-69 [ Show Abstract ]

Purpose
To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).

Methods
Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180.

Results
Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED.

Conclusions
Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.

Das,N., Menon,N., DeAlmeida,L., Woods,P., Heynen,M., Jay,G., Caffery,B., Krawetz,R., Schmidt,T. Dufour,A. Proteomics analysis of tears and saliva from Sjogren’s syndrome patients Frontiers in Pharmacology 2021;12(3299):787193 [ Show Abstract ]

Sjogren's syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tear and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Pathway enrichment analysis of the changing proteins by Metascape identified leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation in tears of SS patients. In healthy controls' tears, an enrichment for proteins related to glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients' saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls' saliva, an enrichment for proteins related to JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients' tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings will improve our mechanistic understanding of the disease and changes in SS patients' protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.

Downie,L. E., Bandlitz,S., Bergmanson,J. P. G., Craig,J. P., Dutta,D., Maldonado-Codina,C., Ngo,W., Sowjanya Siddireddy,J., Wolffsohn,J. S. CLEAR - Anatomy and physiology of the anterior eye Contact Lens Anterior Eye 2021;44(2):132-156 [ Show Abstract ]

A key element of contact lens practice involves clinical evaluation of anterior eye health, including the cornea and limbus, conjunctiva and sclera, eyelids and eyelashes, lacrimal system and tear film. This report reviews the fundamental anatomy and physiology of these structures, including the vascular supply, venous drainage, lymphatic drainage, sensory innervation, physiology and function. This is the foundation for considering the potential interactions with, and effects of, contact lens wear on the anterior eye. This information is not consistently published as academic research and this report provides a synthesis from all available sources. With respect to terminology, the report aims to promote the consistent use of nomenclature in the field, and generally adopts anatomical terms recommended by the Federative Committee for Anatomical Terminology. Techniques for the examination of the ocular surface are also discussed.

Efron,N., Jones,L. W., Morgan,P. B., Nichols,J. J. Bibliometric analysis of the literature relating to scleral contact lenses Contact Lens Anterior Eye 2021;44(4):101447 [ Show Abstract ]

Adolf Eugene Fick, a German ophthalmologist working in Zurich, published the first journal paper on contact lenses in 1888. In this paper, he described the process of fabricating and fitting afocal scleral contact lenses first on rabbits, then on himself and finally on a small group of volunteer patients with keratoconus.

Efron,N., Jones,L. W., Morgan,P. B., Nichols,J. J. On the art and science of rigid contact lens fitting Clinical and Experimental Optometry 2021;104(6):684-690 [ Show Abstract ]

Examination of the literature can help answer the age-old question of the extent to which rigid contact lenses can be considered an art versus a science.

Efron,N., Morgan,P. B., Jones,L. W., Morgan,G. A., Nichols,J. J. Global optometrist top 200 research ranking Clinical and Experimental Optometry 2021;104(4):471-485 [ Show Abstract ]

Clinical relevance: Clinical optometric practice is underpinned by a rigorous research base, the
primary evidence for which is publications in refereed scientific journals. Leading optometrists who
publish this work should be identified and celebrated.
Background: This work aims to derive publication metrics of the leading optometric researchers
worldwide.
Methods: An extensive global search was conducted to discover leading optometric researchers; 480
names were identified. A custom-designed bibliographic search tool was developed to interrogate
the Scopus database (Elsevier) and extract publication metrics using the unique Scopus Author
Identifier number for each optometrist. On 13 January 2021, the full list was reduced to 200
optometrists (the ‘Top 200’) ranked by h-index – the ‘Global Optometrist Top 200 Research
Ranking’. The output from the custom tool automatically updates every 24 hours and is available at
www.optomrankings.com.
Results: The Top 200 have h-indices ranging from 20 to 67 and have published between 28 and 440
papers. Sixty one (30.5%) are women. Konrad Pesudovs has the highest h-index (67) and citations
(51,193). The most prolific author is Robert Hess (442 papers). David Piñero is publishing at the
fastest rate (17.6 papers per year). The Top 200 work in 13 nations, of whom 172 (86.0%) work in
four nations: USA – 76 (38.0%), Australia – 43 (21.5%), UK – 41 (20.5%) and Canada – 16 (8.0%). Of
the 72 institutions represented, the University of California, Berkeley, USA is home to the most Top
200 optometrists (17) and has the highest combined h-index of Top 200 optometrists (132).
Conclusions: The optometric profession is supported by a robust research base, prosecuted by
a large international cohort of optometric researchers who publish extensively on a broad range of
ophthalmic issues and whose work is highly cited. The 200 most impactful optometrists in the world
are identified

Efron,N., Morgan,P. B., Jones,L. W., Nichols,J. J. 21st century citation analysis of the field of contact lenses Clinical and Experimental Optometry 2021;104(5):634-638 [ Show Abstract ]

Clinical relevance: The scientific foundations for clinical contact lens practice are rooted in the ophthalmic literature. This analysis of contact lens papers celebrates contemporary research achievements in the contact lens field.

Background: This work aims to assemble contact lens-related publication metrics so as to identify the most impactful papers published so far this century, as well the top countries, authors, institutions and journals.

Methods: A search was undertaken of the titles of papers on the Scopus database to identify contact lens-related articles published this century. The ten most highly cited papers were determined from the total list of 4,164 papers found. Rank-order lists by count were assembled for the ‘top 25ʹ in each of four categories: authors, institutions, countries and journals. A 20-year subject-specific contact lens h-index (hCL-20-index) was derived for each author, institution, country and journal to serve as a measure of impact in the field. The top 10 constituents (of the top 25) of each category were ranked by hCL-20-index and tabulated for consideration.

Results: The most highly cited paper this century is entitled ‘Soft contact lens polymers: An evolution’, by Nicholson and Vogt. Lyndon Jones is the most impactful author, with a hCL-20-index of 32. The University of New South Wales (Australia) produces the most impactful contact lens-related papers, and the United States is the most highly-ranked country. Optometry and Vision Science is the most impactful journal in the contact lens field.

Conclusions: Contact lens materials and lens-associated keratitis are topics of high interest in the contemporary contact lens literature, with an emerging interest in orthokeratology for myopia control and glucose monitoring. Impactful 21st century authors, institutions, countries and journals are identified. Optometry is revealed as the leading profession in relation to the publication of impactful contact lens-related papers.

Efron,N., Morgan,P. B., Jones,L. W., Nichols,J. J. Bibliometric analysis of the refractive error field Clinical and Experimental Optometry 2021;104(5):641-643 [ Show Abstract ]

Research into the epidemiology, aetiology, and optics of ametropia is a fundamental cornerstone of the correction and management of refractive errors by eye care practitioners. At present, much of this work is driven by the clinical concern that myopia is a common cause of vision loss, with uncorrected myopia the leading cause of vision impairment globally. Holden et al. predict that by 2050, about 50% of the population of the world will be myopic.
The aetiology of myopia continues to be hotly debated, centring around the relative impact of nature (genetics) versus nurture (environment). Research aimed at optimising optical (spectacles and contact lenses) and surgical (laser refractive techniques) modes of correcting refractive error continues unabated, and novel approaches for arresting the progression of myopia, using ophthalmic lenses, contact lenses (including orthokeratology), pharmacological approaches, or lifestyle modification, are also under active investigation. As is the case in all fields of investigation, the foundation of these various lines of refractive error research is rooted in the ophthalmic literature. Modern bibliographic search tools enable targeted interrogation of this vast literature to facilitate identification of the research foundations that underpin our understanding of refractive error. This Viewpoint uses
these bibliographic search tools and employs a subjectspecific measure of impact to identify key papers, authors, institutions, countries, and journals in the field of refractive error research.

Efron,N., Morgan,P. B., Jones,L. W., Nichols,J. J. Bibliometric analysis of the keratoconus literature Clinical and Experimental Optometry 2021;21(Sep):1-6 [ Show Abstract ]

Clinical Relevance
Clinicians, researchers funding agencies and indeed the general public can benefit from knowledge of the most highly cited papers and most impactful authors, institutions, countries and journals in the field of keratoconus.

Background
Bibliometrics relating to the keratoconus literature were derived to enable identification of the most impactful papers published, as well as the leading authors, institutions, countries and journals.

Methods
A search was undertaken of the titles of papers on the Scopus database to identify keratoconus-related articles. The 20 most highly cited papers were determined from the total list of 4,419 papers found. Rank-order lists by count were assembled for the ‘top 20ʹ in each of four categories: authors, institutions, countries and journals. A subject-specific keratoconus-related h-index (hKC-index) was derived for each constituent of each category to serve as a measure of impact in the field. The top 10 constituents of each category were ranked by hKC-index and tabulated for consideration.

Results
The hKC-index of the keratoconus field is 125. The 4,419 papers have been cited a total of 98,010 times, and 18.5% of these papers have never been cited. The most highly cited paper is a general review of keratoconus by Yaron Rabinowitz, who is also the most impactful author in the field (hKC = 31). The Cedars Sinai Medical Center in the United States produces the most impactful keratoconus-related papers (hKC = 36), and the United States is the most impactful country (hKC = 91). The Journal of Cataract and Refractive Surgery is the most impactful journal (hKC = 55).

Conclusion
Keratoconus is a topic of high interest in the clinical and scientific literature. Highly cited papers and impactful authors, institutions, countries and journals are identified.

Efron,N., Morgan,P. B., Jones,L. W., Nichols,J. J. Bibliometric Analysis of the Emerging Field of Myopia Management Optometry & Vision Science 2021;98(9):1039-1044 [ Show Abstract ]

SIGNIFICANCE
Identification of the most impactful articles, authors, institutions, countries, and journals in myopia management provides a useful baseline reference for clinicians, researchers, and funding agencies in respect of this emerging field.

This work aims to assemble publication metrics for myopia management to identify the most impactful articles, authors, institutions, countries, and journals in this emerging field of research. A search of the titles of articles was undertaken on the Scopus database to identify myopia management–related articles. The 25 most highly cited articles were determined from the total list of 1064 articles found. Rank-order lists by count were assembled for the top 25 in each of four categories: authors, institutions, countries, and journals. A subject-specific myopia management–related h-index (hMM-index) was derived for the entire field, in addition to each of the four categories, to serve as measures of impact in the field. Top 15 lists were generated for each category ranked by hMM-index and tabulated for consideration. An article by Christine Wildsoet and colleagues, describing choroidal and scleral mechanisms of compensation for spectacle lenses in chicks, has generated the most citations (412); Earl Smith is the most impactful author (hMM = 19); the University of Houston produces the most impactful articles (hMM = 31); the United States is the most highly ranked country (hMM = 60); and Optometry and Vision Science is the most impactful journal. Although still in its infancy, myopia management is a topic of emerging interest in the clinical and scientific ophthalmic literature. Impactful authors, institutions, countries, and journals are identified. Optometry is revealed as the leading profession in relation to the publication of myopia management–related articles.

Heynen,M., Ng,A., Martell,E., Subbaraman,L. N., Jones,L. Activity of Deposited Lysozyme on Contemporary Soft Contact Lenses Exposed to Differing Lens Care Systems Clinical Ophthalmology 2021;15(April):1727-1733 [ Show Abstract ]

Purpose: The amount of protein deposition on soft contact lenses and to what extent the proteins are denatured may have an impact on comfortable wearing times of contact lenses. The purpose of this study was to evaluate the effects of two lens care systems on total protein and the quantity and activity of lysozyme deposited on worn senofilcon A, silicone hydrogel contact lenses.

Participants and Methods: Thirty symptomatic soft contact lens wearers were enrolled into a 4-week prospective, randomized, bilateral eye, daily-wear, crossover, double-masked study. Participants were fitted with biweekly senofilcon A lenses and were assigned either a polyquaternium-1 and myristamidopropyl dimethylamine-containing system (OPTI-FREE RepleniSH) or a peroxide-based system (CLEAR CARE). After each wear period, proteins were extracted from the lenses and analyzed for total protein, total lysozyme quantity and activity.

Results: The use of either the peroxide-based system or the polyquaternium-1 and myristamidopropyl dimethylamine-containing system resulted in no difference (P> 0.05) to the amount of total protein deposited on the lenses (6.7 ± 2.8 micrograms/lens versus 7.3 ± 2.8 micrograms/lens, respectively) or to the amount of denatured lysozyme deposits (0.8 ± 0.7 versus 0.9 ± 0.7 micrograms/lens), respectively. The total amount of lysozyme deposited on the lenses was significantly lower when using the peroxide-based system (1.3 ± 0.9 micrograms/lens) compared to the polyquaternium-1 and myristamidopropyl dimethylamine-containing system (1.7 ± 1.0 micrograms/lens) (P=0.02).

Conclusion: The inactivation of lysozyme deposited on senofilcon A lenses when disinfected with the peroxide-based or the polyquaternium-1 and myristamidopropyl dimethylamine-containing systems were neither statistically nor clinically significant and the overall amounts of denatured lysozyme recovered from the lenses were low (< 1 microgram/lens).

Huynh,C. B., Ngo,W. Quantifying the Effect of Spectacle Frame Dimensions on Wind-Induced Ocular Plane Evaporation Using an in Vitro Model Eye & Contact Lens 2021;47(347):351 [ Show Abstract ]

Purpose: To quantify the effect of spectacle frame dimensions on wind-induced ocular plane evaporation.

Methods: A drop of 0.5 μL water was pipetted onto an eye of a mannequin head. The face was fitted with a spectacle frame. A fan positioned 10 cm away directed air (185 CFM) toward the face and the time required for the drop to evaporate was recorded. This procedure was repeated with 31 different frames to obtain evaporation times for various eye sizes, vertical heights, vertex distances, temperature, and humidity. This was also repeated 30 times without spectacle wear to obtain evaporation times for various temperature and humidity conditions.

Results: Spectacle wear increased evaporation times compared with nonspectacle wear, in both high (>35%) and low humidity (<30%) conditions (both P<0.01). Humidity was correlated with evaporation time, regardless of spectacle and nonspectacle wear (both P<0.01). Evaporation time did not correlate with spectacle eye size, vertical height, or vertex distance (all P≥0.21).

Conclusion: This study showed that spectacle wear guarded against wind-induced evaporation at the ocular plane compared with nonspectacle wear. However, once spectacles were worn, eye size, vertical height, and vertex distance were not correlated with evaporation times. Humidity drove evaporation independent of spectacle wear.

Jin,Y., Dixon,B., Jones,L., Gorbet,M. The Differential Reactive Oxygen Species Production of Tear Neutrophils in Response to Various Stimuli In Vitro International Journal of Molecular Sciences 2021;22(23):12899 [ Show Abstract ]

A large number of polymorphonuclear neutrophils (PMNs) invade the ocular surface during prolonged eye closure (sleep); these leukocytes are commonly referred as tear PMNs. PMNs contribute to homeostasis and possess an arsenal of inflammatory mediators to protect against pathogens and foreign materials. This study examined the ability of tear PMNs to generate reactive oxygen species (ROS), an essential killing mechanism for PMNs which can lead to oxidative stress and imbalance. Cells were collected after sleep from healthy participants using a gentle eye wash. ROS production in stimulated (phorbol-12-myristate-13-acetate (PMA), lipopolysaccharides (LPS) or N-Formylmethionyl-leucyl-phenylalanine (fMLP)) and unstimulated tear PMNs was measured using luminol-enhanced chemiluminescence for 60 min. A high level of constitutive/spontaneous ROS production was observed in tear PMNs in the absence of any stimulus. While tear PMNs were able to produce ROS in response to PMA, they failed to appropriately respond to LPS and fMLP, although fMLP-stimulated tear PMNs generated ROS extracellularly in the first three minutes. Higher ROS generation was observed in isolated tear PMNs which may be due to priming from the magnetic bead cell separation system. The differential responses of tear PMNs in ROS generation provide further evidence of their potential inflammatory roles in ocular complications involving oxidative stress.

Jones,L., Hui,A., Phan,C-M., Read,M. L., Azar,D., Buch,J., Ciolino,J. B., Naroo,S. A., Pall,B., Romond,K., Saknaridurg,P., Schnider,C. M., Terry,L., Willcox,M. CLEAR - Contact lens technologies of the future Contact Lens Anterior Eye 2021;44(2):398-430 [ Show Abstract ]

Contact lenses in the future will likely have functions other than correction of refractive error. Lenses designed to control the development of myopia are already commercially available. Contact lenses as drug delivery devices and powered through advancements in nanotechnology will open up further opportunities for unique uses of contact lenses.

This review examines the use, or potential use, of contact lenses aside from their role to correct refractive error. Contact lenses can be used to detect systemic and ocular surface diseases, treat and manage various ocular conditions and as devices that can correct presbyopia, control the development of myopia or be used for augmented vision. There is also discussion of new developments in contact lens packaging and storage cases.

The use of contact lenses as devices to detect systemic disease has mostly focussed on detecting changes to glucose levels in tears for monitoring diabetic control. Glucose can be detected using changes in colour, fluorescence or generation of electric signals by embedded sensors such as boronic acid, concanavalin A or glucose oxidase. Contact lenses that have gained regulatory approval can measure changes in intraocular pressure to monitor glaucoma by measuring small changes in corneal shape. Challenges include integrating sensors into contact lenses and detecting the signals generated. Various techniques are used to optimise uptake and release of the drugs to the ocular surface to treat diseases such as dry eye, glaucoma, infection and allergy. Contact lenses that either mechanically or electronically change their shape are being investigated for the management of presbyopia. Contact lenses that slow the development of myopia are based upon incorporating concentric rings of plus power, peripheral optical zone(s) with add power or non-monotonic variations in power. Various forms of these lenses have shown a reduction in myopia in clinical trials and are available in various markets.

Khanal,S., Ngo,W., Nichols,K. K., Wilson,L., Barnes,S., Nichols,J. J. Human meibum and tear film derived (O-acyl)-omega-hydroxy fatty acids in meibomian gland dysfunction Ocular Surface 2021;21(July):118-128 [ Show Abstract ]

Purpose: The molecular basis of the tear film and lipid layer alterations in meibomian gland dysfunction (MGD) is unknown. This study aimed to identify and compare (O-acyl)-omega-hydroxy fatty acids (OAHFAs) derived from human meibum and tears in MGD. Methods: Of 195 eligible subjects (18–84 years, 62.6% female), 183 and 174 provided samples for tears and meibum, respectively. Subjects were classified into four groups: Normal, Asymptomatic MGD, MGD, and Mixed. Samples from the right eye of each subject were infused into the SCIEX 5600 TripleTOF mass spectrometer in negative ion mode. Lipid intensities identified with Analyst1.7 TF and SCIEX LipidView1.3 were normalized by an internal standard and total ion current, then statistically compared in MetaboAnalyst 4.0. Results: In meibum and tears, 76 and 78 unique OAHFAs were identified, respectively. The five most frequent and abundant OAHFAs were 18:2/16:2, 18:1/32:1, 18:1/30:1, 18:2/32:1, and 18:1/34:1. Two OAHFAs, 18:2/20:2 and 18:2/20:1, were identified only in tears. Initial univariate analysis revealed three differently regulated OAHFAs in meibum and eight in tears. Partial Least Square Discriminant Analysis showed 18:1/32:1, 18:2/16:2, 18:1/34:1 and 18:0/32:1 in tears, and 18:2/16:2, 18:1/32:1 and 18:2/32:2 in meibum, had variable importance in projection scores >1.5 and contributed the most to the separation of groups. In both meibum and tears, all OAHFAS except 18:2/16:2 were reduced in MGD compared to the normal group. Conclusion: MGD is accompanied by differential expression of specific OAHFAs in meibum and tears. These results suggest OAHFAs play a role in the altered biochemical profile of the tear film lipid layer in humans with MGD.

Kondela,T., Dushanov,E., Vorobyeva,M., Mamatkulov,K., Drolle,E., Soloviov,D., Hrubovcak,P., Kholmurodov,K., Arzumanyan,G., Leonenko,Z., Kucerka,N Investigating the competitive effects of cholesterol and melatonin in model lipid membranes Biochimica et Biophysica Acta - Biomembranes 2021;1863(9):183651 [ Show Abstract ]

We have studied the impact of cholesterol and/or melatonin on the static and dynamical properties of bilayers made of DPPC or DOPC utilizing neutron scattering techniques, Raman spectroscopy and molecular dynamics simulations. While differing in the amplitude of the effect due to cholesterol or melatonin when comparing their interactions with the two lipids, their addition ensued recognizable changes to both types of bilayers. As expected, based on the two-component systems of lipid/cholesterol or lipid/melatonin studied previously, we show the impact of cholesterol and melatonin being opposite and competitive in the case of three-component systems of lipid/cholesterol/melatonin. The effect of cholesterol appears to prevail over that of melatonin in the case of structural properties of DPPC-based bilayers, which can be explained by its interactions targeting primarily the saturated lipid chains. The dynamics of hydrocarbon chains represented by the ratio of trans/gauche conformers reveals the competitive effect of cholesterol and melatonin being somewhat more balanced. The additive yet opposing effects of cholesterol and melatonin have been observed also in the case of structural properties of DOPC-based bilayers. We report that cholesterol induced an increase in bilayer thickness, while melatonin induced a decrease in bilayer thickness in the three-component systems of DOPC/cholesterol/melatonin. Commensurately, by evaluating the projected area of DOPC, we demonstrate a lipid area decrease with an increasing concentration of cholesterol, and a lipid area increase with an increasing concentration of melatonin. The demonstrated condensing effect of cholesterol and the fluidizing effect of melatonin appear in an additive manner upon their mutual presence.

Mirzapour,P., McCanna,D. J., Jones,L. In vitro analysis of the interaction of tear film inflammatory markers with contemporary contact lens materials Contact Lens Anterior Eye 2021;44(5):101430 [ Show Abstract ]

Purpose
Several clinical studies have suggested that reusable silicone hydrogel contact lens materials exhibit a two-times increased rate of corneal infiltrative events compared to reusable hydrogels. One potential factor contributing to this complication relates to the differential uptake of tear film-based pro-inflammatory cytokines. The purpose of this study was to use an in vitro assay to investigate whether four pro-inflammatory cytokines differed in their uptake onto six contemporary contact lens materials.

Methods
Conventional hydrogel (etafilcon A, omafilcon A) and silicone hydrogel (balafilcon A, comfilcon A, senofilcon A, somofilcon A) contact lens materials were soaked in solutions containing pro-inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α. Samples of the soaking solutions were collected over various time points and analyzed using the Meso Scale Discovery system, which served as a measurement of cytokine uptake onto the contact lens materials.

Results
Both conventional hydrogels (etafilcon A, omafilcon A) and two of the four silicone hydrogels tested (balafilcon A, comfilcon A), exhibited some uptake of IL-1β, IL-8 or TNF-α (p 0.05). There was no uptake of IL-6 onto any of the contact lens materials investigated (p > 0.05).

Conclusion
The contact lens materials tested did not exhibit any uptake of IL-6 and furthermore, did not exhibit more than 10 ± 3 % to 25 ± 12 % uptake of IL-1β, IL-8 or TNF-α. Numerous factors could contribute to the reported increase in corneal infiltrative events with reusable silicone hydrogel materials, however, based on these results, it appears that uptake of these four cytokines are unlikely to contribute to this finding.

Morgan,P. B., Murphy,P. J., Gifford,K. L., Gifford,P., Golebiowski,B., Johnson,L., Makrynioti,D., Moezzi,A. M., Moody, K., Navascues-Cornago,M., Schweizer,H., Swiderska,K., Young,G., Willcox,M. CLEAR - Effect of contact lens materials and designs on the anatomy and physiology of the eye Contact Lens Anterior Eye 2021;44(2):192-219 [ Show Abstract ]

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia).

However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation.

In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.

Nichols,J. J., Jones,L., Morgan,P. B., Efron,N. Bibliometric analysis of the meibomian gland literature Ocular Surface 2021;20(April):212-214 [ Show Abstract ]

There is a rich history of interest in the sebaceous glands located posterior to the tarsal plates in the eyelids, to which we refer today as the meibomian glands (MGs). Although there is acknowledgement of the MGs preceding the work of Johann Heinrich Meibom in the 1600's, he is credited with advancing our knowledge and study of these glands.

The MGs produce a distinct lipid secretion (‘meibum’) made up of a variety of lipid classes, mostly composed of nonpolar wax and cholesterol esters, although other nonpolar and polar lipids are certainly known to exist in the meibum. The normal function of meibum is to make its way to the tear film lipid layer, ultimately forming a resistive barrier to evaporation of the aqueous component of the tear film. In disease, the MGs lose their ability to secrete a normal meibum composition and/or are impeded due to factors such as atrophy of the MGs, keratinization of the orifice of the gland from which the meibum is secreted onto the eyelid margin, or bacterial colonization of the eyelid, altering the secretion itself once expressed. These conditions today are known as blepharitis, including anterior and posterior blepharitis (which includes meibomian gland dysfunction).

Given the extensive study of MGs, a bibliometric analysis is warranted to acknowledge and celebrate those contributing to this important part of ophthalmic research.

Nichols,J. J., Jones,L., Morgan,P. B., Efron,N. Bibliometric analysis of the orthokeratology literature Contact Lens Anterior Eye 2021;44(4):101390 [ Show Abstract ]

The wearing of rigid lenses can result in changes to corneal curvature and the planned, temporary reduction of myopia by wearing flat-fitting rigid lenses (termed orthokeratology) was first reported in the 1960’s [1]. In the late 1970’s and early 1980’s, several studies evaluated this concept and concluded that the reduction in myopia was relatively short-lived, unpredictable, inconsistent and limited to only a low degree of myopia; as such, orthokeratology was largely ignored at this time [2, 3, 4].
A renewed interest in orthokeratology occurred in the late 1990’s and early 2000’s due to the simultaneous development of corneal topographers, highly oxygen permeable rigid lens materials and the development of sophisticated reverse geometry lenses that produced more predictable reductions in myopia [5, 6, 7, 8, 9]. This permitted contact lens fitters to adopt the concept of ‘overnight orthokeratology’, where patients wore the lenses during sleep and corneal shape changes occurred that reduced the degree of myopia to the point where the patient could remove the lens on waking and spend several days with no vision correction being required [10,11].
In 2005, Cho and colleagues reported that orthokeratology lenses used in children could slow the progression of myopia and this observation resulted in a resurgence in interest in orthokeratology [12]. Numerous publications since have shown that this myopia control effect is repeatable and many practitioners now adopt this modality on a routine basis to slow the progression of myopia, particularly in Asian countries [9,13, 14, 15, 16, 17].
The purpose of this paper is to report a bibliometric analysis of the literature on orthokeratology lenses so as to determine the most widely cited papers and most prolific authors, institutions, countries and journals related to this topic, and to recognise and celebrate the key stakeholders in this area of contact lens research.

Nichols,J. J., Morgan,P. M., Jones,L. W., Efron,N 21st century bibliometric analysis of the field of dry eye disease Clinical and Experimental Optometry 2021;104(5):639-640 [ Show Abstract ]

In 2012, the lead author of this paper (JJN) conducted a citation analysis of dry eye research to identify the leading papers, authors, institutions, countries and journals in the field. That analysis was essentially an historical overview of publications on this topic extending back over the past century. Because a strong and growing foundation of scientific literature is a fundamental component of evidenced-based clinical care of patients, the current work was conducted to update the research community on trends in the 21st century dry eye literature, and to compare this new literature with the prior analysis in the context of events or trends in the dry eye field.

Omali,N. B., Subbaraman,L. N., Heynen,M., Lada,M., Canavan,K., Fadli,Z., Ngo,W., Jones,L. Lipid deposition on contact lenses in symptomatic and asymptomatic contact lens wearers Cont Lens Anterior Eye 2021;44(1):56-61 [ Show Abstract ]

Purpose
Lipid deposition on contact lenses (CL) has traditionally been believed to reduce comfort during CL wear. The purpose of this study was to quantify lipid deposition on CL in a group of symptomatic and asymptomatic adapted CL wearers.

Methods
This was a single-masked, randomized clinical trial. Only confirmed symptomatic (comfortable lens wear time (CWT) 10 h and minimal reduction in comfort over the course of the day) participants were recruited to participate in the study. Participants wore senofilcon A lenses in combination with a polyquaternium-based care solution (OPTI-FREE Replenish). Worn CL samples were collected on Day 14. Deposited lipid amounts from the lenses (including cholesteryl ester, cholesterol and triolein) were quantified using a liquid chromatography-mass spectrometry technique.

Results
Lipid deposition was significantly higher in CL extracts of asymptomatic wearers compared to the symptomatic wearers for all lipid types quantified, including cholesteryl ester (2.1 ± 0.6 vs 1.6 ± 0.5 log μg/lens), cholesterol (1.5 ± 0.3 vs 1.1 ± 0.3 log μg/lens) and triolein (0.3 ± 0.2 vs 0.1 ± 0.1 log μg/lens) (all p < 0.002). The amount of cholesteryl ester deposited was greatest (p = 0.0001), followed by cholesterol, then triolein, for both the asymptomatic and symptomatic groups (both p = 0.0001).

Conclusion
This study demonstrated that the asymptomatic group deposited a significantly greater amount of lipid on their CL. Although lipid levels measured are considered low to trigger any observable clinical deposition, they may influence other clinical outcomes, particularly comfort.

Phan,C. M., Qiao,H., Yee,A., Jones,L. Deposition of Fluorescently Tagged Lysozyme on Contact Lenses in a Physiological Blink Model Eye & Contact Lens 2021;47(2):127-133 [ Show Abstract ]

PURPOSE: To visualize the deposition of fluorescein isothiocyanate (FITC) lysozyme on daily disposable contact lenses (CLs) using a novel blink model.

METHODS: Three daily disposable conventional hydrogel CLs (etafilcon A, omafilcon A, and nelfilcon A) and three silicone hydrogel CLs (delefilcon A, senofilcon A, and somofilcon A) were evaluated in the study. The CLs were mounted onto a novel blink model and exposed to an artificial tear solution containing FITC lysozyme for 2 and 10 hr. The flow rate and blink speed were set to 1 μL/min and 6 blinks/min, respectively. After the incubation period, a 5-mm-diameter disc was punched out from the center of the lens and mounted on a microscope slide. The slides were imaged using the Zeiss 510 Meta confocal laser scanning microscope, which scanned the lens from the front to the back surface at 5-μm increments.

RESULTS: There was an increase in deposition of FITC lysozyme for all lens types with increasing incubation time (P0.05). The conventional hydrogel CLs deposited higher amounts of FITC lysozyme than the silicone hydrogel CLs (P<0.001), with etafilcon A depositing the highest at all time points (P<0.05). Interestingly, at the 2-hr incubation time, most CLs showed a higher amount of deposition at the front surface than the back surface of the lens. In particular, etafilcon A showed preferred deposition at the front surface at all time points.

CONCLUSION: The results suggest that there is differential deposition at the front surface of the CL, which is exposed to the prelens tear film, compared with the back surface of the CL, which is exposed to the postlens tear film. Therefore, it may be beneficial to design CL materials with differing surface properties for the front and back surfaces of the CL to enhance interactions with the tear film and ocular surface.

Phan,C. M., Shukla,M., Walther,H., Heynen,M., Suh,D., Jones,L. Development of an In Vitro Blink Model for Ophthalmic Drug Delivery Pharmaceutics 2021;13(Article 300):1-10 [ Show Abstract ]

Purpose: The purpose of this study was to develop an advanced in vitro blink model that
can be used to examine the release of a wide variety of components (for example, topical ophthalmic
drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using
computer-aided design software and printed using a stereolithography 3D printer. The eyelid and
eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated
tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each
blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The
flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and
senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye
model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min.
Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation,
nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL)
than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau
profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was
sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05).
Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye
model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure
the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink
mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better
results than a simple, static vial incubation model.

Schulze,M., Ng,A. Y., Yang,M., Panjwani,F., Srinivasan,S., Jones,L., Senchyna,M. Bulbar redness and dry eye disease: comparison of a validated subjective grading scale and an objective automated method Optometry & Vision Science 2021;98(2):113-120 [ Show Abstract ]

SIGNIFICANCE
In this study, assessments of conjunctival redness were performed to evaluate whether patients with or without dry eye disease (DED) could be discriminated based on this measure. Our findings suggest that subjectively grading redness by quadrant, as opposed to automated en face measurements, may be more suitable for this purpose.

PURPOSE
This study aimed to quantify bulbar redness using the validated bulbar redness (VBR) grading scale and an automated objective method (Oculus Keratograph 5M; K5M) in participants with DED and non-DED controls.

METHODS
Participants with DED (Ocular Surface Disease Index score ≥20 and Oxford scale corneal staining ≥2) and controls (Ocular Surface Disease Index score ≤10 and corneal staining ≤1) attended two study visits. In part 1A of visit 1, baseline bulbar redness was graded with the VBR scale in each conjunctival quadrant of both eyes, followed by automated measurements of temporal and nasal redness with the K5M. This was immediately followed by part 1B, during which a topical vasoconstrictor was instilled into both eyes. Redness assessments were repeated 5 and 30 minutes after instillation with both instruments. Participants returned 14 days later for visit 2, where the same assessments as for visit 1A were repeated.

RESULTS
Seventy-four participants (50 DED and 24 controls) completed the study. There were statistically significant differences in redness between the DED and control groups when assessed with the VBR scale (14/16 comparisons; all, P < .05), whereas no significant differences in K5M-derived redness between the DED and non-DED groups were found at any location or time point. Both subjective and objective instruments detected statistically significant reductions in redness 5 and 30 minutes after instillation of the vasoconstrictor (all, P < .01).

CONCLUSIONS
Although both subjective and objective instruments were sensitive to detecting changes in redness induced by vasoconstriction, statistically significant differences in redness between DED and control groups were only found using the VBR scale.

Spafford,M. M., Jones,D. A., Christian,L. W., Labreche,T., Furtado,N. M., MacIver,S., Irving,E. L. What the Canadian public (mis)understands about eyes and eye care Clinical and Experimental Optometry 2021;Online ahead of print [ Show Abstract ]

Clinical relevance
Inadequate public knowledge about eyes and eye care poses avoidable risks to vision-related quality of life.

Background
This study of eye care knowledge among Canadians extends earlier findings from focus groups.

Methods
Perceptions about eyes and eye care were sought using a 21-item online survey and snowball sampling. Inclusion criteria were living in Canada and being at least 18-years old; eye care professionals and staff were excluded. Response frequencies were converted to percentages, with eye condition items analysed according to ‘expected’ or ‘unexpected’ eye impacts. Proportions selecting these impacts or ‘unsure’ were determined.

Results
There were 424 respondents: 83.0% aged 20-65 years and 69.6% female. Mismatches existed between perceived recommendations and behaviours for booking eye exams: within two years (86.7% vs. 68.4%) and symptom-driven (3.3% vs. 13.0%). First eye exams after age one year were deemed appropriate by 43.6%. Few respondents associated glaucoma with no symptoms (6.0%) or amblyopia with blurred vision (13.5%). A notable proportion incorrectly related tunnel vision with age-related macular degeneration (AMD, 36.8%) and cataract (21.9%). Identifying all ‘expected’ responses was unlikely for glaucoma (1.9%), amblyopia (6.7%), and cataract (12.0%). Most respondents identified no ‘expected’ effects for glaucoma (63.8%) and AMD (46.2%) and some ‘expected’ effects for cataract (59.5%) and amblyopia (72.6%). Selecting ‘unsure’ was 9-10 times more common among respondents choosing no ‘expected’ impacts than those choosing some. Awareness of thyroid-associated eye disease was lowest (32.4%) of seven conditions. Respondents were most likely to consult optometrists for routine eye exams, eye disease, diabetes eye checks and blurred vision but family physicians for red eyes and sore eyes. Respondents typically paid for their eye exams and eyewear but wanted government to pay.

Conclusion
Vision-threatening knowledge gaps and misinformation about eyes and eye care among Canadian respondents highlight the need for accessible, targeted public education.

Stapleton,F., Bakkar,M., Carnt,N., Chalmers,R., Kumar Vijay,A., Marasini,S., Ng,A. Y., Tan,J., Wagner,H., Woods,C., Wolffsohn,J. S. CLEAR - Contact lens complications Contact Lens Anterior Eye 2021;44(2):330-367 [ Show Abstract ]

Contact lens-related complications are common, affecting around one third of wearers, although most are mild and easily managed. Contact lenses have well-defined anatomical and physiological effects on the ocular surface and can result in other consequences due to the presence of a biologically active material. A contact lens interacts with the tear film, ocular surface, skin, endogenous and environmental microorganisms, components of care solutions and other antigens which may result in disease specific to contact lens wear, such as metabolic or hypersensitivity disorders. Contact lens wear may also modify the epidemiology or pathophysiology of recognised conditions, such as papillary conjunctivitis or microbial keratitis. Wearers may also present with intercurrent disease, meaning concomitant or pre-existing conditions unrelated to contact lens wear, such as allergic eye disease or blepharitis, which may complicate the diagnosis and management of contact lens-related disease.

Complications can be grouped into corneal infection (microbial keratitis), corneal inflammation (sterile keratitis), metabolic conditions (epithelial: microcysts, vacuoles, bullae, tight lens syndrome, epithelial oedema; stromal: superficial and deep neovascularisation, stromal oedema [striae/folds], endothelial: blebs, polymegethism/ pleomorphism), mechanical (corneal abrasion, corneal erosion, lens binding, warpage/refractive error changes; superior epithelial arcuate lesion, mucin balls, conjunctival epithelial flaps, ptosis, discomfort), toxic and allergic disorders (papillary conjunctivitis, solution-induced corneal staining, incomplete neutralisation of peroxide, Limbal Stem Cell Deficiency), tear resurfacing disorders/dry eye (contact lens-induced dry eye, Meibomian gland dysfunction, lid wiper epitheliopathy, lid parallel conjunctival folds, inferior closure stain, 3 and 9 o'clock stain, dellen, dimple veil) or contact lens discomfort. This report summarises the best available evidence for the classification, epidemiology, pathophysiology, management and prevention of contact lens-related complications in addition to presenting strategies for optimising contact lens wear.

Thite,N., Desiato,A., Shinde,L., Wolffsohn,J. S., Naroo,S. A., Santodomingo-Rubido,J., Cho,P., Jones,D., Villar-Collar,C., Carillo,G., Chan,O., Wang,H., Iomdina,E., Tattura,E., Proskurina,O., Shing Fan,C., Zeri,F., Bakkar,M. M., Barodawala,F., Dabral,N., Lafosse,E., Lee,C., Nichols,J. J., Chan,J., Park,K., Nair,V., van der Worp,E., Vankudre,G., Maseedupalli,V., Bhattarai,Y., Nagzarkar,D., Brauer,P., Gil-Cazorla,R. Opportunities and threats to contact lens practice: A global survey perspective Contact Lens Anterior Eye 2021;44(6):101496 [ Show Abstract ]

Aim
To understand the views of contact lens (CL) practitioners across the globe regarding what they perceive as opportunities and threats in CL practice.

Methods
A self-administered anonymised questionnaire, constructed in English and translated in six more languages, was distributed through reputed international professional bodies and academic institutions worldwide. The questionnaire included items on demographic characteristics, type of practice, and questions designed to explore practitioners’ perspective on the future of their CL practice over the next five years.

Results
A total of 2408 valid responses were analysed. Multifocal CLs for presbyopia, CLs for myopia control, use of daily disposable (DD) CLs for occasional wear, and biocompatible materials to improve comfort were identified as promising areas of opportunities by practitioners (all 8/10). Respondents from North America, and Europe valued DDCLs for occasional wear moderately more favourable (Median: 9/10 for all) as compared to colleagues in Asia (Median: 8/10, p < 0.001), South America (Median: 8/10, p < 0.01), and Africa (Median: 8/10p < 0.01). Multifocal CLs for presbyopia was perceived as a better opportunity by practitioners in North America and Europe (Median: 9/10 for both), as well as in Australasia (Median: 8/10), in comparison to Asia, Africa, and Middle East (for all Median: 6/10, p < 0.001). Practitioners expressed concerns about the availability of CLs and CL prescriptions online without direct professional involvement (both 9/10).

Conclusions
Overall, the most appealing opportunities for CL practice growth were identified in occasional use of DD CLs, biocompatible materials to reduce CL discomfort, multifocal CLs for presbyopia correction and management of myopia control with CLs. Lack of regulation in CL sales, especially online, seemed to be a constant threat. The insights from this study can be used to design targeted strategies to enhance CL practice across the globe and in specific geographical areas.

Tichenor,A., Cofield,S., Gann,D., Elder,M., Ng,A. Y., Walsh,K., Jones,L., Nichols,J. Frequency of Contact Lens Complications Between Contact Lens Wearers Using Multipurpose Solutions Versus Hydrogen Peroxide in the United States and Canada Eye & Contact Lens 2021;47(5):277-282 [ Show Abstract ]

Objectives: To retrospectively compare frequency of contact lens (CL) complications in soft CL users of hydrogen peroxide (H2O2) and multipurpose solutions (MPS).

Methods: This was a multicenter, retrospective chart review of CL records from each patient's three most recent eye examinations at academic and private practices. Patients must have used the same solution type for at least 3 years. Univariate analyses were conducted using t tests, and chi-square or Fisher's exact test for categorical measures.

Results: There were 1,137 patients included, with 670 (59%) using MPS and 467 (41%) H2O2. In total, 706 (62%) experienced at least one complication; 409 used MPS and 297 used H2O2. There was no difference in the proportion of patients experiencing at least one complication between MPS (61%) and H2O2 (64%) (P=0.38). Multipurpose solutions users were more likely to report discomfort compared with H2O2 users (P=0.04). Presumed microbial keratitis was experienced by 16 MPS and nine H2O2 users (P=0.60).

Conclusions: No significant differences were found in the frequency of CL complications between MPS and H2O2. H2O2 users were less likely to report discomfort and thus switching to a H2O2 system may be an alternative in CL users with discomfort.

Ulkuseven,E., McCanna,D. J., Subbaraman,L. N., Jones,L. W. The Effect of Antimicrobial Peptides on the Viability of Human Corneal Epithelial Cells Probiotics and Antimicrobial Proteins 2021;13(2):518-526 [ Show Abstract ]

Antimicrobial peptides are polypeptides composed of less than 100 amino acids and are a class of antibiotics with strong activity against some infectious bacteria. This study examined the safety of four chosen antimicrobial peptides using primary human corneal epithelial cells (HCEC) and explored their potential therapeutic use. The efficacy of the peptides was also studied by evaluating the minimum inhibitory concentrations (MIC) against Gram-negative and Gram-positive bacteria. One of the peptides (polymyxin E) was found to have antibacterial efficacy against a common Gram-negative bacterium (MIC 1.56 μg/mL for Pseudomonas aeruginosa), and another one (nisin) was found to have antibacterial efficacy against a common Gram-positive bacterium (MIC 125 μg/mL for Staphylococcus aureus). Metabolic activity and live/dead/apoptotic effects were measured with fluorescent dyes after HCEC were exposed to the peptides for 30 min. Three of the peptides exhibited lower toxicity against HCEC than a currently marketed eye drop product. Regarding both efficacy and safety, two of the peptides (polymyxin E and nisin) were found to have potential use for treating ocular infections.

Vincent,S. J., Cho,P., Yin Chan,K., Fadel,D., Ghorbani-Mojarrad,N., González-Méijome,J. M., Johnson,L., Michaud,L., Simard,P., Jones,L. CLEAR - Orthokeratology Contact Lens Anterior Eye 2021;44(2):240-269 [ Show Abstract ]

Orthokeratology (ortho-k) is the process of deliberately reshaping the anterior cornea by utilising specialty contact lenses to temporarily and reversibly reduce refractive error after lens removal. Modern ortho-k utilises reverse geometry lens designs, made with highly oxygen permeable rigid materials, worn overnight to reshape the anterior cornea and provide temporary correction of refractive error. More recently, ortho-k has been extensively used to slow the progression of myopia in children.

This report reviews the practice of ortho-k, including its history, mechanisms of refractive and ocular changes, current use in the correction of myopia, astigmatism, hyperopia, and presbyopia, and standard of care. Suitable candidates for ortho-k are described, along with the fitting process, factors impacting success, and the potential options for using newer lens designs. Ocular changes associated with ortho-k, such as alterations in corneal thickness, development of microcysts, pigmented arcs, and fibrillary lines are reviewed. The safety of ortho-k is extensively reviewed, along with an overview of non-compliant behaviours and appropriate disinfection regimens. Finally, the role of ortho-k in myopia management for children is discussed in terms of efficacy, safety, and potential mechanisms of myopia control, including the impact of factors such as initial fitting age, baseline refractive error, the role of peripheral defocus, higher order aberrations, pupil size, and treatment zone size.

Walther,H., Lorentz,H., Heynen,M., Kay,L., Jones,L. W. The Impact of Incubation Conditions on in Vitro Phosphatidylcholine Deposition on Contact Lens Materials Optometry & Vision Science 2021;98(4):341-349 [ Show Abstract ]

SIGNIFICANCE: Previous in vitro measurements of contact lenses commonly investigate the impact of nonpolar
tear film lipids (i.e., sterols). Polar lipids, however, are equally important stabilizing components of the tear film.
This research explores and presents further knowledge about various aspects of polar lipid uptake that may impact
contact lens performance.

PURPOSE: This study evaluated the impact of incubation time, lipid concentration, and replenishment of an artificial
tear solution (ATS) on the uptake of phosphatidylcholine (PC) onto conventional hydrogel (CH) and silicone
hydrogel (SH) contact lens materials.

METHODS: Four SHs and two CH lens materials (n = 4) were soaked in a complex ATS containing radioactive
14C-PC as a probe molecule. Phosphatidylcholine uptake was monitored at various incubation time points (1, 3,
7, 14, and 28 days), with different ATS lipid concentrations (0.5, 1, 2) and with and without regular replenishment
of the ATS. Phosphatidylcholine was extracted from the lenses, processed, and counted by a β counter,
and accumulated PC (μg/lens) was extrapolated from standard lipid calibration curves.

RESULTS: All materials exhibited increasing PC deposition over time. Conventional hydrogel materials showed significantly lower PC uptake rates (P < .001) than any of the SH materials. Increasing lipid concentration in the ATS
resulted in increased PC binding onto the contact lens materials (P < .001). Replenishing the ATS every other day,
however, impacted the PC deposition differently, showing increased binding (P < .001) on CHs and reduced PC
deposition for SH materials (P < .001).

CONCLUSIONS: Length of incubation, lipid concentration in the ATS, and renewal of the incubation solution all
influenced the amount of PC that sorbed onto various lens materials and therefore need to be considered when
conducting future in vitro deposition studies.

Willcox,M., Keir,N., Maseedupallu,V., Masoudi,S., McDermott,A., Mobeen,R., Purslow,C., Santodomingo-Rubio,J., Tavazzi,S., Zeri,F., Jones,L. W. CLEAR - Contact lens wettability, cleaning, disinfection and interactions with tears Contact Lens Anterior Eye 2021;44(2):157-191 [ Show Abstract ]

Contact lens materials have undergone significant changes over the past 20 years, particularly with respect to the introduction of silicone hydrogel materials. Whilst this development addressed hypoxic issues, other important areas relating to contact lens success, notably comfort, require further research.

Contact lens wettability remains a crucially important part of biocompatibility. Contact lenses can be made more wettable by incorporation of surfactants into blister packs, internal wetting agents, surface treatments or care solutions. However, there remains no clear association between contact lens wettability and comfort, making it challenging to determine the potential for these approaches to be of significant clinical benefit. Most contact lenses are used on a daily wear, reusable basis, which requires them to be disinfected when not worn. The ideal disinfecting solution would also improve comfort during wear. However, balancing these requirements with other factors, including biocompatibility, remains a challenge. Soft lens materials invariably take up and subsequently release certain components of disinfecting solutions onto the ocular surface. This may affect tear film stability and the normal ocular microbiome, and further research is needed in this area to determine whether this has any affect on comfort. Finally, contact lens materials sorb components of the tear film, and these interactions are complex and may change the biochemistry of the tear film, which in turn may affect their comfort.

In conclusion, the interaction between lens materials, tear film and disinfection solution plays an important role in the biocompatibility of lenses. However, the exact role and whether this can be altered to improve biocompatibility and comfort during wear remains debatable. This report summarises the best available evidence to examine this complex relationship and the opportunities for practitioners to enhance in-eye comfort of contemporary lenses, along with providing suggestions for areas of study that may provide further information on this topic.

Wolffsohn,J. S., Dumbleton,K., Huntjens,B., Kandel,H., Koh,S., Kunnen,C. M. E., Nagra,M., Pult,H., Sulley,A. L., Vianya-Estopa,M., Walsh,K., Wong,S., Stapleton,F. CLEAR - Evidence-based contact lens practice Contact Lens Anterior Eye 2021;44(2):368-397 [ Show Abstract ]

Evidence-based contact lens -->practice involves finding, appraising and applying research findings as the basis for patient management decisions. These decisions should be informed by the strength of the research study designs that address the question, as well as by the experience of the practitioner and the preferences and environment of the patient. This reports reviews and summarises the published research evidence that is available to inform soft and rigid contact lens history and symptoms taking, anterior eye health examination (including the optimised use of ophthalmic dyes, grading scales, imaging techniques and lid eversion), considerations for contact lens selection (including the ocular surface measurements required to select the most appropriate lens parameter, lens modality and material selection), evaluation of lens fit, prescribing (teaching self-application and removal, adaptation, care regimen and cleaning instructions, as well as -->minimising risks of lens wear through encouraging compliance) and an aftercare routine.

Wolffsohn,J. S., Morgan,P. B., Barnett,M., Downie,L. E., Jacobs,D. S. Jones,L. W., Richdale, K., Stapleton,F., Vincent,S. J., Willcox,M. Contact Lens Evidence-Based Academic Reports (CLEAR) Contact Lens Anterior Eye 2021;44(2):129-131 [ Show Abstract ]

Since contact lenses were invented in 1887, innovations have included advances in optical design, material, care systems, wear modality, lens size, lens shape and applications. Over 19,000 peer reviewed academic papers on the contact lenses have been published. The Contact Lens Evidence-based Academic Reports (CLEAR) follow the exemplary work of organisations such as the Tear Film and Ocular Surface Society dry eye, meibomian gland disease, contact lens discomfort and dry eye II workshops and the International Myopia Institute white papers on myopia control, in collating and appraising the academic literature in an ocular field of interest. CLEAR represent the work of nearly 100 multidisciplinary experts in the field, who set out to critically review, synthesise and summarise the research evidence on contact lenses to date; this serves to inform both clinical practice, manufacturing innovation and future research directions.

Wolffsohn,J. S., Travé-Huarte,S., Jones,L., Craig,J. P., Wang,M. T. M., the TFOS ambassadors. Clinical practice patterns in the management of dry eye disease: A TFOS international survey Ocular Surface 2021;21(July):78-86 [ Show Abstract ]

Purpose
To examine clinical management and prescribing patterns for dry eye disease (DED), in relation to severity and subtype, by eye care practitioners across the globe.

Methods
An online, anonymous cross-sectional survey (on Qualtrics) translated into 14 languages was distributed to eye care practitioners across the globe. The survey included six questions around the management of DED, in relation to severity and subtype.

Result
The survey was completed by 1139 eyecare professionals (37% ophthalmologists and 58% optometrists) from 51 countries. Management varied significantly by continent and country (p < 0.01). The most commonly recommended management approaches, internationally, included general advice (87%), low (85%) and high (80%) viscosity-enhancing unpreserved lubricants and lid wipes/scrubs (81%). Some treatments were prescribed largely independently of severity (e.g. artificial tears and nutritional supplements) while oral antibiotics, punctal occlusion, topical anti-inflammatory/immunosuppressants, secretagogues, biologics, therapeutic contact lenses and surgical approaches were prescribed by more practitioners as severity increased. Essential fatty acids, lipid sprays/drops, lid hygiene, warm compresses, intense pulsed light therapy and antibiotics (topical or oral) were more commonly recommended for evaporative DED, while punctal occlusion, therapeutic contact lenses, secretagogues and biologics were more commonly recommended for aqueous deficient DED.

Conclusions
DED management differs across continents and countries. A wide range of management strategies are utilised at each severity level and between subtypes. The survey results enable clinicians to benchmark their practice to that of their peers, indicate where further research is required to optimise patient management and inform industry on how best to target product development.

Woods,J., Jones,D., Jones,L., Jones,S., Hunt,C., Chamberlain,P., McNally,J Ocular health of children wearing daily disposable contact lenses over a 6-year period Contact Lens Anterior Eye 2021;44(4):101391 [ Show Abstract ]

Purpose
To report on the ocular health and safety of children fit with soft hydrogel daily-disposable contact lenses, and followed for 6-years in a double-masked clinical trial investigating the performance of a dual-focus contact lens designed to control myopia progression.

Methods
Children aged 8−12 years, naïve to contact lens wear, were enrolled across four international sites. During years 1–3, children were randomised to either MiSight® 1 day or Proclear® 1 day (both omafilcon A, CooperVision, Inc.). The lenses were identical in material and geometry except for the front optical zone design. At the end of year-3, all those wearing Proclear 1 day were switched to MiSight 1 day, therefore all wore MiSight 1 day in years 4−6. Subjects agreed to wear the lenses at least 10-hours/day, 6-days/week. After dispensing, study visits were at 1-week, 1-month, 6-months and every 6-months until 6-years. At each visit, ocular measurements and subjective responses were recorded. Biomicroscopy used 0–4 grading scales; grade 0 represented no findings.

Results
144 children were enrolled: 69F:75M; mean age 10.1 years; mean cycloplegic spherical-equivalent refraction -2.11D; ethnicities included 34 East-Asian, 12 West-Asian, and 79 Caucasian. 92 completed the 6-years. Only three subjects discontinued due to an ocular adverse event (AE). No contact lens related AEs were classified as serious. The incidence rate of infiltrative AEs was 0.61% (6.1/1000 wearing-years; 95%CI: 0.24%–1.57%). The most common biomicroscopy findings were limbal, bulbar and tarsal hyperaemia and tarsal roughness. 99% of all biomicroscopy findings were grade-1 or lower. After 6-years of lens wear, ocular health by biomicroscopy was similar to pre-lens wear.

Conclusions
Across the 6-years, there were no contact lens related serious AEs and biomicroscopy showed no significant changes. Results suggest that children this age can successfully wear daily-disposable hydrogel contact lenses with minimal impact on ocular physiology.

Xu,M., Sivak,J. G., McCanna,D. J. Neutralization of the eye and skin irritant benzalkonium chloride using UVC radiation Cutaneous and Ocular Toxicology 2021;40(2):78-84 [ Show Abstract ]

Benzalkonium chloride (BAK) is a widely used disinfectant and preservative which is effective against a wide range of viruses (e.g. SARS-CoV and SARS-CoV-2), bacteria and fungi. However, it is toxic to the eye and skin. This study investigated the neutralization of BAK using ultraviolet C (UVC) radiation as an effort to reduce BAK toxicity potential.

Methods
BAK solutions were irradiated with a germicidal UVC lamp at various doses. Human corneal epithelial cells (HCEC) were then exposed to the UVC-irradiated BAK solutions for 5 minutes. After exposure, the cultures were assessed for metabolic activity using PrestoBlue; for cell viability using confocal microscopy with viability dyes; and for tight junction proteins using immunofluorescence staining for zonula occludens (ZO)-1.

Results
UVC radiation reduced BAK toxicity on cell metabolic activity in a dose-dependent manner. When the solution depth of BAK was 1.7 mm, the UVC doses needed to completely neutralize the toxicity of BAK 0.005% and 0.01% were 2.093 J/cm2 and 8.374 J/cm2, respectively. The cultures treated with UVC-neutralized BAK showed similar cell metabolic activity and cell viability to those treated with phosphate buffered saline (PBS) (p = 0.806 ∼ 1.000). The expression of ZO-1 was greatly disturbed by untreated BAK; in contrast, ZO-1 proteins were well maintained after exposure to UVC-neutralized BAK.

Conclusions
Our study demonstrates that the cell toxicity of BAK can be neutralized by UVC radiation, which provides a unique way of detoxifying BAK residues. This finding may be of great value in utilizing the antimicrobial efficacy of BAK (e.g. fighting against SARS-CoV-2) while minimizing its potential hazards to human health and the environment.

Yamasaki,K., Drolle,E., Nakagawa,H., Hisamuare,R., Ngo,W., Jones,L. W. Impact of a low molecular weight hyaluronic acid derivative on contact lens wettability Cont Lens Anterior Eye 2021;44(3):101334 [ Show Abstract ]

Purpose
To investigate the interaction of a novel low molecular weight hyaluronic acid derivative containing hydrophobic groups with soft contact lenses and its effect on lens hydrophilicity compared with a conventional form of hyaluronic acid.

Methods
This investigation studied the uptake of fluorescently-labelled hyaluronic acid and a low molecular weight hyaluronic acid derivative to four types of contact lenses using fluorescent microscopy and confocal laser scanning microscopy. Further, the four lens types were used to compare efficacy in improving hydrophilicity, as well as maintenance of contact angle measurements, in commercially available multipurpose solutions that contained either hyaluronic acid, the low molecular weight hyaluronic acid derivative, or an alternative wetting agent.

Results
The low molecular weight hyaluronic acid derivative was found to sorb more readily to silicone hydrogel lenses and exhibit a greater accumulation over time than conventional hyaluronic acid. Multipurpose solutions containing the low molecular weight hyaluronic acid derivative showed an increase in lens hydrophilicity through decreases in contact angle measurements when compared with those obtained from lenses treated with multipurpose solutions containing conventional hyaluronic acid or alternative wetting agents. This increase in lens hydrophilicity associated with the low molecular weight hyaluronic acid derivative was also maintained over multiple cycles in phosphate buffered saline, while alternative solutions with conventional hyaluronic acid did not.

Conclusion
Overall, lens treatment using a low molecular weight hyaluronic acid derivative-based solution lead to improved in vitro lens hydrophilicity.

Yamasaki,K., Mizuno,Y., Kitamura,Y., McCanna,D. J., Ngo,W., Jones,L. W. The efficacy of povidone-iodine, hydrogen peroxide and a chemical multipurpose contact lens care system against Pseudomonas aeruginosa on various lens case surfaces Cont Lens Anterior Eye 2021;44(1):18-23 [ Show Abstract ]

Purpose
To determine the antimicrobial efficacy of a povidone-iodine system (PVP-I; cleadew, OPHTECS Corporation, Kobe, Japan), a peroxide system (AOSEPT Plus with HydraGlyde, Alcon, Fort Worth, TX), and a chemical multipurpose system (renu fresh, Bausch & Lomb, Rochester, NY) on contact lens case surfaces that are both in contact and not in contact with the solutions during lens disinfection.

Methods
The surfaces of the inner walls, underside of the lid, and lens holder (if applicable) of the cases were inoculated with P. aeruginosa ATCC 27853. The cases were disinfected with the solutions as per their manufacturer instructions. After disinfection, the inoculated surfaces were swabbed and the amount of surviving P. aeruginosa was determined. Following this experiment, separate cases were inoculated and disinfected as before. This time the cases were agitated after recommended disinfection time and the amount of P. aeruginosa in the disinfecting solution was quantified immediately, and again after resting for 7 days. Experiments were conducted in triplicate (n = 3).

Results
Units are expressed in log CFU. All three solutions significantly reduced P. aeruginosa on direct-contact surfaces (all p < 0.039). On non-contact surfaces, the reduction of P. aeruginosa in the PVP-I system (pre-disinfection: 6.8 ± 0.5, post-disinfection: 1.0 ± 0.0; p < 0.001) was significant, but not for the hydrogen peroxide system (pre-disinfection: 6.3 ± 0.6, post: 5.5 ± 0.5; p = 0.194) and the chemical multipurpose system (pre-disinfection: 6.6 ± 0.1, post-disinfection: 5.6 ± 0.8; p = 0.336). After 7 days post-disinfection, no P. aeruginosa regrowth was observed in the PVP-I system (Day 1: 1.0 ± 0.0, Day 7: 1.0 ± 0.0; p = 1) and the chemical multipurpose system (Day 1: 4.2 ± 0.2, Day 7: 1.8 ± 0.9; p = 0.012), however regrowth was observed in the hydrogen peroxide system (Day 1: 3.4 ± 0.6, Day 7: 6.1 ± 0.4; p = 0.003).

Conclusion
The PVP-I system was more effective against P. aeruginosa on non-contact surfaces than the hydrogen peroxide system or the chemical multipurpose system and is capable of inhibiting regrowth of P. aeruginosa for at least 7 days post-disinfection.

Yang,M., Ngo,W., Srinivasan,S., Heynen,M. L., Dantam,J., Subbaraman,L. N., Jones,L., Senchyna,M. Optimization of goblet cell density quantification methods Experimental Eye Research 2021;207(June):108607 [ Show Abstract ]

The purpose of this study was to develop a standardized, accurate and efficient method for estimating conjunctival goblet cell density (GCD) via optimizing sample storage conditions and quantification methods. Conjunctival impression cytology (CIC) membranes were collected from both eyes of 32 participants and were randomized to two storage durations (2-3 weeks, 6-7 weeks) and two storage container types (microcentrifuge tube, flat histology cassette). The CIC membranes were stained and subdivided into 25 areas (5 mm × 5 mm) for imaging and the GCs were counted under 200X magnification using three different methods: (1) full CIC membrane GC count of the 25 images with cell-counting software ("full"; reference method), (2) partial membrane GC count of 9 images with cell-counting software ("partial"), and (3) manual counting of the 25 images ("manual"). In all cases, GCD was determined by dividing the GC count by the counting area. The average time required for quantification was recorded to gauge efficiency. Results showed no significant difference in GC count between the two storage durations (p = 0.745) or storage container types (p = 0.552). The median (interquartile range (IQR)) time required to quantify a CIC membrane for the full, partial, and manual methods of GC counting, was 14.8(17.6), 4.6(5.2) and 5.0 (5.0) minutes, respectively. The agreement of GCD values between the full and manual methods (bias: 0.4, 95% LOA: [-4.6, 5.5]) was stronger than that comparing the full and partial methods (bias: 0.5, 95% LOA: [-18, 17]). All together, through systematic examination of key procedural variables, an optimized method for GCD quantification within 7 weeks of sample collection was outlined. Adaption of procedures described in this paper to facilitate accurate and efficient GCD quantification may serve as a valuable step in clinical trials investigating DED pathophysiology and/or novel DED treatment strategies.

Yee,A., Chan,V., Heynen,M., Phan,C. M., Jones,L. Uptake and release of a multipurpose solution biocide (MAP-D) from hydrogel and silicone hydrogel contact lenses using a radiolabel methodology Eye & Contact Lens 2021;47(5):249-255 [ Show Abstract ]

Purpose:
The purpose of this study was to evaluate the uptake and release of radiolabelled myristamidopropyl dimethylamine (MAP-D) on reusable daily wear contact lenses (CLs) over 7 days.

Methods:
Three silicone hydrogel (SH) CL materials (lotrafilcon B, balafilcon A, senofilcon A) and two conventional hydrogel (CH) materials (etafilcon A, omafilcon A) were tested. A short-term (experiment 1, N=4) and a longer-term (experiment 2, N=3) study was conducted. In experiment 1, the CLs were incubated in 2 mL of phosphate buffered solution (PBS) containing 14C MAP-D (5 μg/mL) for 8 hrs. The release of 14C MAP-D was measured at t=0.25, 0.5, 1, 2, 4, 8, and 24 hr in PBS. In experiment 2, the CLs were incubated in the 14C MAP-D solution for 8 hrs followed by a 16-hr release in PBS. This cycle was repeated daily for 7 days. At the end of both experiments, lenses were extracted to determine the total uptake of MAP-D. The radioactivity was measured using a beta scintillation counter.

Results:
In experiment 1, all three SH lenses sorbed similar amounts of MAP-D (P=0.99), all of which were higher than the two CH materials (P<0.01). However, the CH materials released a greater amount of MAP-D than the SH materials (P<0.01). In experiment 2, the uptake of MAP-D in SH materials increased over 7 days, whereas the amount of MAP-D remained constant in the CH materials (P=0.99). Similar to experiment 1, the CH lenses released more MAP-D than SH lenses after 7 days (P<0.01).

Conclusion:
The SH materials absorbed greater amounts of MAP-D compared to CH materials. However, the CH materials released the greatest amount of MAP-D. Radioactive labelling of MAP-D offers a highly sensitive method of assessing the uptake and release profiles of biocides to CL materials.

Yee,A., Walsh,K., Schulze,M., Jones,L The impact of patient behaviour and care system compliance on reusable soft contact lens complications Contact Lens Anterior Eye 2021;44(5):101432 [ Show Abstract ]

Reusable soft daily wear contact lenses (CLs) remain popular and were fit to just over half of all wearers in the most recent international CL prescribing survey. Unlike daily disposable CLs, reusables require cleaning and disinfecting after every use, along with storage in a CL case. These additional requirements add a number of steps to the daily wear and care routine, increasing the opportunities for CL wearers to exhibit non-compliant behaviour. The impact of non-compliance ranges from poor lens comfort through to potentially sight- threatening infective keratitis. The coronavirus pandemic has refocused the profession on the importance of hand hygiene in particular, and the need for promoting safe CL wear in general. This review summarises typical non-compliant behaviour related to reusable CLs, and examines strategies and opportunities to better support wearers. Patient education has a central role in encouraging compliant behaviour, although patient recall of information is low, and personal belief systems may result in continuation of non-compliant behaviour despite awareness of the risks. CL care solutions are required for the daily disinfection of lenses, however misuse of multipurpose solutions (MPS) and hydrogen peroxide (H2O2)-based care systems can challenge their ability to be fully efficacious. Standard efficacy testing is reviewed, with consideration of how well current protocols model real-world use of CL solutions. Although some recommendations are in place for the inclusion of additional variables such as lens cases, CL materials, organic soil and efficacy against Acanthamoeba, opportunity still exists to reevaluate global standards to ensure consistency of testing in all markets. Finally, potential future innovations are discussed which may further support increased safety in reusable lens wear through novel antimicrobial additions to both CL materials and cases

2020

Bitton,E., Elder,M., Srinivasan,S., Luensmann,D., Jones,L. Dry Eye Disease in University-based Clinics in Canada: A Retrospective Chart Review Optometry & Vision Science 2020;97(11):944-953 [ Show Abstract ]

SIGNIFICANCE
Dry eye disease (DED) imposes a substantial burden on patients, which can lead to significant economic consequences for society. We provide insights into the DED patient population and DED diagnostic/management practices in Canada, which to date have been inadequately addressed in the literature.

PURPOSE
The purpose of this study was to describe DED patient demographic/clinical characteristics alongside DED diagnosis/management in university-based optometry clinics in Canada.

METHODS
This was a retrospective chart review of nonconcurrent non-Sjögren patients with DED at two university-based optometry clinics in Montreal and Waterloo. Waterloo charts with a diagnosis of DED and all charts from the Montreal dry eye clinic were considered for inclusion.

RESULTS
Overall, 200 charts were reviewed. Most patients were female (Montreal, 76%; Waterloo, 72%), and the mean age was 57.2 ± 14.9 years at Montreal and 52.6 ± 20.1 years at Waterloo. Patients commonly reported multiple health conditions (e.g., allergies [Montreal, 44%; Waterloo, 36%]), and high use of systemic nonocular medications was observed (Montreal, 76%; Waterloo, 62%). Clinical signs and symptoms of DED were recorded more often in Montreal patients than in Waterloo patients (e.g., dryness symptoms, 100 vs. 72%; tear breakup time, 100 vs. 60%). Warm compresses (Montreal, 63%; Waterloo, 83%) and artificial tears (Montreal, 94%; Waterloo, 96%) were the most frequently recommended nonmedical treatment and ocular lubricant, respectively. Topical steroids were the most frequently prescribed medications (Montreal, 22%; Waterloo, 21%), with typically three to four different interventions recommended per patient at each clinic. No relationship was found between symptoms and clinical signs or recommended interventions.

CONCLUSIONS
This retrospective chart review provided the demographics, clinical characteristics, diagnosis, and management options for DED patients in Canadian university-based optometry clinics. The more comprehensive assessments conducted at Montreal may be beneficial to better monitor the progression of DED and to determine treatment effects over time.

Cheung,S., Subbaraman,L. N., Ngo,W., Jay,G. D., Schmidt,T. A., Jones,L. Localization of full-length recombinant human proteoglycan-4 in commercial contact lenses using confocal microscopy Journal of Biomaterials Science, Polymer Edition 2020;31(1):110-122 [ Show Abstract ]

The aim of this study was to determine the sorption location of full-length recombinant human proteoglycan 4 (rhPRG4) tagged with fluorescein isothiocyanate (FITC) to four silicone hydrogel contact lenses [balafilcon A (PureVision, Bausch + Lomb), senofilcon A (Acuvue Oasys, Johnson & Johnson), comfilcon A (Biofinity, CooperVision), lotrafilcon B (Air Optix, Alcon)] and one conventional hydrogel lens [etafilcon A (Acuvue 2, Johnson & Johnson)], using confocal laser scanning microscopy (CLSM). Lenses (n = 3 each) were incubated under two conditions: (1) FITC-rhPRG4 solution at 300 μg/mL and (2) phosphate-buffered saline, for 1 h at 37 °C in darkness with gentle shaking. The central 4 mm of each lens was removed and viewed with the Zeiss 510 CLSM using an argon laser at 488 nm (FITC excitation 495 nm, emission 521 nm). Depth scans were taken at 1 μm intervals to a maximum depth of 100 μm. All lens materials demonstrated sorption of rhPRG4. Both senofilcon A and balafilcon A revealed FITC-rhPRG4 penetration into the bulk of the lens, generally favoring the surface. rhPRG4 was observed exclusively on the surface of lotrafilcon B, with no presence within the bulk of the lens. rhPRG4 was evenly distributed throughout the bulk of the lens, as well as on the surface, for comfilcon A and etafilcon A. The sorption profile of FITC-rhPRG4 was successfully visualized using CLSM in various contact lens materials. The polymer composition, surface treatment and pore size of the material can influence the sorption of rhPRG4.

Dantam,J., Subbaraman,L. N., Jones,L. Adhesion of Pseudomonas aeruginosa, Achromobacter xylosoxidans, Delftia acidovorans, Stenotrophomonas maltophilia to contact lenses under the influence of an artificial tear solution Biofouling 2020;36(1):32-43 [ Show Abstract ]

Corneal infection is a devastating sight-threatening complication that is associated with contact lens (CL) wear, commonly caused by Pseudomonas aeruginosa. Lately, Achromobacter xylosoxidans, Delftia acidovorans, and Stenotrophomonas maltophilia have been associated with corneal infection. This study investigated the adhesion of these emerging pathogens to CLs, under the influence of an artificial tear solution (ATS) containing a variety of components commonly found in human tears. Two different CL materials, etafilcon A and senofilcon A, either soaked in an ATS or phosphate buffered saline, were exposed to the bacteria. Bacterial adhesion was investigated using a radio-labeling technique (total counts) and plate count method (viable counts). The findings from this study revealed that in addition to P. aeruginosa, among the emerging pathogens evaluated, A. xylosoxidans showed an increased propensity for adherence to both CL materials and S. maltophilia showed lower viability. ATS influenced the viable counts more than the total counts on CLs.

Desai,A. R., Maulvi,F. A., Desai,D. M., Shukla,M. R., Ranch,K. M., Vyas,B. A., Shah,S. A., Sandeman,S., Shah,D. O. Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release Materials Science and Engineering: C 2020;112(July):110885 [ Show Abstract ]

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Drolle,E., Ngo,W., Leonenko,Z., Subbaraman,L., Jones,L. Nanoscale Characteristics of Ocular Lipid Thin Films Using Kelvin Probe Force Microscopy 2020;9(7):1-11 [ Show Abstract ]

Purpose: To describe the use of Kelvin probe force microscopy (KPFM) to investigate the electrical surface potential of human meibum and to demonstrate successful use of this instrument on both human meibum and a meibum model system (six-lipid stock [6LS]) to elucidate nanoscale surface chemistry and self-assembly characteristics.

Materials and Methods: 6LS and meibum were analyzed in this study. Mica-supported thin films were created using the Langmuir-Blodgett trough. Topography and electrical surface potential were quantified using simultaneous atomic force microscopy/KPFM imaging.

Results: Both lipid mixtures formed thin film patches on the surface of the mica substrate, with large aggregates resting atop. The 6LS had aggregate heights ranging from 41 to 153 nm. The range in surface potential was 33.0 to 125.9 mV. The meibum thin films at P = 5 mN/m had aggregates of 170 to 459 nm in height and surface poten- tial ranging from 15.9 to 76.1 mV, while thin films at P = 10 mN/m showed an aggregate size range of 147 to 407 nm and a surface potential range of 11.5 to 255.1 mV.

Conclusions: This study showed imaging of the differences in electrical surface poten- tial of meibum via KPFM and showed similarities in nanoscale topography. 6LS was also successfully analyzed, showing the capabilities of this method for use in both in vitro and ex vivo ocular research.

Translational Relevance: This study describes the use of KPFM for the study of ocular surface lipids for the first time and outlines possibilities for future studies to be carried out using this concept.

Efron,N., Brennan,N. A., Chalmers,R. L., Jones,L. W., Lau,C., Morgan,P. B., Nichols,J. J., Szczotka-Flynn,L. B., Willcox,M. D. Thirty years of ‘quiet eye’ with etafilcon A contact lenses Contact Lens Anterior Eye 2020;43(3):285-297 [ Show Abstract ]

Frequent replacement contact lenses made from the etafilcon A hydrogel lens material were introduced onto the market over 30 years ago, and etafilcon A remains the most widely used hydrogel lens material today. Although the prescribing of silicone hydrogel lenses is increasing, millions of lens wearers globally have been wearing hydrogel lenses for many years and exhibit a physiologically-stable ‘quiet eye’, with a low profile of adverse events. Hydrogel lenses are demonstrated to maintain a low inflammatory response and infection risk profile during daily wear, which in the case of etafilcon A, may be related to its low modulus, and the naturally-protective, anti-microbial, non-denatured lysozyme absorbed into the lens from the tear fluid. Although improved corneal physiology from decreased hypoxia with silicone hydrogel lenses is well accepted, equivalent levels of corneal oxygenation are maintained during daily wear of low to medium powered hydrogel lenses, which do not impede the daily corneal de-swelling process, and do not induce clinically significant changes in ocular health. Therefore, hydrogel lenses remain an important alternative for daily wear in modern contact lens practice.

Jin,Y., Jones,L., Gorbet,M. Investigation of the response of tear-film neutrophils to interleukin 8 and their sensitivity to centrifugation, fixation, and incubation Scientific report 2020;10(1):19690 [ Show Abstract ]

During eye closure, a large number of neutrophils (polymorphonuclear neutrophils, PMNs) invade the ocular surface and are often referred to as tear-film PMNs. While immunophenotyping experiments have been performed on tear-film PMNs, the impact of commonly used experimental procedures on their phenotype as well as their response to interleukin-8 (IL-8), a physiological inflammatory mediator, have not yet been investigated. A gentle eye wash method was used to collect cells at home. In the morning upon awaking, participants washed their eyes with sterile phosphate buffer saline (PBS) and collected the runoff into a sterile polypropylene tube. The cell collection was then delivered to the lab within two hours. The effects of centrifugation, incubation and fixation with paraformaldehyde (PFA) before (pre-fixed staining) or after (post-fixed staining) incubation with antibodies were characterized. Tear-film PMNs as well as blood PMNs (used for comparison) were also stimulated with IL-8. To assess the reproducibility of cell collection and variability in receptor expression over time, participants were also asked to collect cells three times over a period of a month. The change in expression of surface receptors, CD11b, CD16, CD55, CD66b, important inflammatory and activation markers, and CD45 (PAN leukocyte marker) was assessed by flow cytometry. Fixing tear-film PMNs prior to the staining with antibodies resulted in a significant (fivefold or more) reduction in the expression of CD11b, CD16 and CD45 when compared to unfixed samples, while CD16 was the only receptor to undergo significant downregulation upon post-staining fixation. Furthermore, additional centrifugation step prior to antibody incubation as well as long (4 h) incubation at 37 °C resulted in significant reductions in expression of CD11b, CD16 and CD55 when compared to control samples. As opposed to blood PMNs, stimulating tear-film PMNs with IL-8 did not induce any significant changes in expression of CD11b, CD16, CD55 and CD66b. When working with collected tear-film PMNs, our results suggest that any additional centrifugation and incubation step should be avoided, or at least limited, and post fixation staining is recommended in order to preserve cell phenotype and cell integrity of tear film PMNs. Our study also adds further information on the reproducibility of the gentle eye wash as well as the inability of tear-film PMNs to modulate their surface receptors upon stimulation with IL-8. The latter may be due to prior exposure to IL-8, activation in the closed-eye environment, or a reduced ability to respond to inflammatory stimulus. Further mechanistic studies will be needed to gain a better understanding of the tear-film neutrophil phenotype.

Jones,L., Walsh,K., Willcox,M., Morgan,P., Nichols,J. The COVID-19 pandemic: Important considerations for contact lens practitioners Cont Lens Anterior Eye 2020;43(3):196-203 [ Show Abstract ]

A novel coronavirus (CoV), the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), results in the coronavirus disease 2019 (COVID-19). As information concerning the COVID-19 disease continues to evolve, patients look to their eye care practitioners for accurate eye health guidance. There is currently no evidence to suggest an increased risk of contracting COVID-19 through contact lens (CL) wear compared to spectacle lens wear and no scientific evidence that wearing standard prescription spectacles provides protection against COVID-19 or other viral transmissions.

During the pandemic there will potentially be significant changes in access to local eyecare. Thus, it is imperative CL wearers are reminded of the steps they should follow to minimise their risk of complications, to reduce their need to leave isolation and seek care. Management of adverse events should be retained within optometric systems if possible, to minimise the impact on the wider healthcare service, which will be stretched. Optimal CL care behaviours should be the same as those under normal circumstances, which include appropriate hand washing (thoroughly with soap and water) and drying (with paper towels) before both CL application and removal. Daily CL cleaning and correct case care for reusable CL should be followed according to appropriate guidelines, and CL exposure to water must be avoided. Where the availability of local clinical care is restricted, practitioners could consider advising patients to reduce or eliminate sleeping in their CL (where patients have the appropriate knowledge about correct daily care and access to suitable lens-care products) or consider the option of moving patients to daily disposable lenses (where patients have appropriate lens supplies available). Patients should also avoid touching their face, including their eyes, nose and mouth, with unwashed hands and avoid CL wear altogether if unwell (particularly with any cold or flu-like symptoms).

Luensmann,D., Omali,N. B., Suko,A., Drolle,E., Heynen,M., Subbaraman,L. S., Scales,C., Fadli,Z., Jones,L. Kinetic Deposition of Polar and Non-polar Lipids on Silicone Hydrogel Contact Lenses Current Eye Research 2020;45(12):1477-1483 [ Show Abstract ]

Purpose: This study investigated kinetic lipid uptake to four silicone hydrogel (SiHy) lenses over a period of four weeks, using an in-vitro radiolabel method.

Methods: Four contemporary monthly replacement SiHy lenses (lotrafilcon B, senofilcon C, comfilcon A, samfilcon A) were incubated in three different solutions: 1) An artificial tear solution (ATS) containing 14C-labeled phosphatidylcholine (PC), 2) an ATS containing 14C-cholesteryl oleate (CO) and 3) an ATS containing four 14C-radiolabeled lipids (PC, phosphatidylethanolamine, CO, and cholesterol (total lipid)). After 16 hours, lipids were extracted twice from the lenses with chloroform:methanol and the radioactive counts determined the lipid quantities to simulate 1 day of wear. OPTI-FREE PureMoist (Alcon) was used to clean and disinfect the remaining lenses daily and the lipid quantities were further determined after 2 weeks and 4 weeks.

Results: The amount of total lipid increased for all lenses over time (p < .01). After four weeks, total lipid accumulated was 20.26 ± 0.15 µg/lens for senofilcon C, which was significantly higher (p < .01) than all other lens materials (samfilcon A - 17.84 ± 0.21; comfilcon A - 16.65 ± 0.12; lotrafilcon B - 7.41 ± 0.56 µg/lens). CO was highest on lotrafilcon B (1.26 ± 0.13 µg/lens) and senofilcon C attracted the most PC (3.95 ± 0.12 µg/lens) compared to the other materials.

Conclusion: The amount of both polar and non-polar lipid deposition on monthly replacement SiHy lenses increased over 4 weeks, with significant differences being seen between lens materials.

Luensmann,D., van Doorn,K., May,C., Srinivasan,S., Jones,L. The Impact of Cosmetics on the Physical Dimension and Optical Performance of Contemporary Silicone Hydrogel Contact Lenses Eye & Contact Lens 2020;46(3):166-173 [ Show Abstract ]

Purpose: Contact lens wearers may inadvertently expose their lenses during the lens insertion and removal process or while wearing their lenses to cosmetic products being used. This study investigated the impact of
various cosmetics on the physical dimension and optical properties of three recently marketed monthly replacement silicone hydrogel contact lenses.

Methods: In this in vitro study, three monthly replacement silicone hydrogel lens types including senofilcon C (ACUVUE VITA, Johnson & Johnson), samfilcon A (Bausch+Lomb ULTRA, Bausch+Lomb), and lotrafilcon
B+EOBO (polyoxyethylene-polyoxybutylene) (AIR OPTIX plus HydraGlyde, ALCON), were individually coated with cosmetic products followed by a 1-hr soak in phosphate-buffered saline. Cosmetic products
included; three hand creams (HC1: Glysomed; HC2: Vaseline Healthy Hand & Nail Conditioning; and HC3: Intense Relieve), three make-up removers (MR1: Lid-Care Towelettes; MR2: Gentle waterproof eye and
Lip Makeup Remover; and MR3: Oil-Free Makeup Remover), and three mascaras (MA1: Great Lash—waterproof; MA2a: Wonder’Lash—waterproof, and MA3: Voluminous Original). The contact lens dimensions were
determined for diameter, sagittal depth, and base curve, using the Chiltern (Optimec Limited), whereas lens power and optical quality were assessed using the Contest Plus II (Rotlex). Six replicates for each lens/cosmetic combination were used. The impact of cosmetics was tested between lenses and compared with uncoated control lenses.

Results: For lens diameter, makeup removers (MR2 & MR3) demonstrated the largest impact, with an increase of up to 0.26 mm (MR2) and 0.35 mm (MR3) for senofilcon C and samfilcon A, respectively (P,0.01 compared to baseline), whereas lotrafilcon B+EOBO showed a decrease of 0.01 mm (P,0.01 between lens types). For sagittal depth, mascara MA1 demonstrated the greatest impact, followed by makeup removers MR2 & MR3. All lenses showed increases in sagittal depth after MA1 exposure (0.1660.06 mm in lotrafilcon B+EOBO, 0.2460.22, and 0.2660.09 mm in samfilcon A and senofilcon C, respectively; P,0.01 for all lenses compared with baseline). For base curve, the makeup removers (MR2 & MR3) caused increases for both senofilcon C (up to 0.36 mm) and samfilcon A (up to 0.35 mm), but lotrafilcon B+EOBO was unaffected. Lens power changes were generally minor (,0.25 D). However, senofilcon C showed a significant change of 21.1860.65 D (more minus) after MA1 exposure (P,0.001). Image quality was most affected by mascaras, although given that all lens types were adversely affected to similar degrees, none of the lenses performed better or worse after mascara application (P.0.05). The parameters of the different lens types were not significantly affected by the hand creams.

Conclusion: Makeup removers and mascaras changed the lens parameters to varying degrees, which may affect the fit and overall performance of the lens, whereas no such effect was noted with hand creams. Lotrafilcon B+EOBO was typically less affected compared with senofilcon C or samfilcon A.

Maulvi,F. A., Parmar,R. J., Desai,A. R., Desai,M. D., Shukla,M. R., Ranch,K. M., Shah,S. A., Shah,D. O. Tailored gatifloxacin Pluronic® F-68-loaded contact lens: Addressing the issue of transmittance and swelling. International journal of pharmaceutics International Journal of Pharmaceutics 2020;581(May 15):119279 [ Show Abstract ]

Loading of gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and gatifloxacin loading capacity as well as sustained drug delivery. Optimization of gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and gatifloxacin loading capacity of 92.56 μg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo gatifloxacin release data for rabbit tear fluid showed sustained release with a high gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.

Maulvi,F. A., Patel,P. J., Soni,P. D., Desai,A. R., Desai,D. T., Shukla,M. R., Ranch,K. M., Shah,S. A., Shah,D. O. Novel Poly(vinylpyrrolidone)-Coated Silicone Contact Lenses to Improve Tear Volume During Lens Wear: In Vitro and In Vivo Studies ACS Omega 2020;5(29):18148-18154 [ Show Abstract ]

Poly(vinylpyrrolidone) (PVP-K90) is widely used to manage dry eye syndrome (DES). The marketed eye drop solutions (high dose) need frequent instillation, affecting the routine lifestyle of patients. PVP-K90-laden contact lenses can be used to overcome the limitations of eye drop solutions (low bioavailability and frequent instillation). However, the conventional methods of PVP-K90 loading show poor loading capacity and short duration of effect. In the present study, we have developed PVP-K90-coated contact lenses via a short curing approach to increase the PVP-K90 loading capacity with a sustained release profile to manage dry eye syndrome. PVP-K90 was loaded by a soaking method (SM-PVP), direct loading (during fabrication, DL-PVP), a combination of soaking and direct loading (DL-SM-PVP), and a novel coating process (SM-PVP-C and DL-SM-PVP-C). The swelling studies suggested improvement in the water uptake (hydration) property of the contact lenses due to the presence of PVP-K90. The optical transparency was within an acceptable range. The in vitro release of PVP-K90 was in the following order: PVP-coated contact lens (168 h) > DL-SM-PVP (168 h) > DL-PVP (96 h) > SM-PVP (72–96 h). PVP-coated contact lenses showed a high burst effect (lubricating effect) and sustained release (3161–448 ng/h between 24 and 168 h) due to high PVP loading/coating in comparison to the uncoated respective contact lenses (964–113 ng/h between 24 and 96 h). In animal studies, the PVP-K90-coated contact lens showed higher tear volume in comparison to the respective uncoated contact lenses and an eye drop solution. This study demonstrates a novel approach of coating a high amount of PVP-K90 on contact lenses for sustained release to manage several ocular diseases like dry eye syndrome, conjunctivitis, and other ocular injuries.

Muntz,A., Subbaraman,L.N., Craig,J. P., Jones,L. Cytomorphological assessment of the lid margin in relation to symptoms, contact lens wear and lid wiper epitheliopathy Ocular Surface 2020;18(2):214-220 [ Show Abstract ]

Purpose: Lid wiper epitheliopathy (LWE) is insufficiently understood from a cytological perspective. This study explored the relationship between lid margin cytomorphology, LWE, contact lens wear, and lens-related symptoms. Methods: Habitual, symptomatic (n = 20) and asymptomatic (n = 20) soft, rigid gas permeable (n = 18) and non-contact lens wearers (n = 19) were enrolled. LWE was graded using lissamine green and the Korb scale. Subjective symptoms were assessed using the Ocular Surface Disease Index and the Contact Lens Dryness Evaluation Questionnaire. Impression cytology samples obtained from the central upper and lower lid margins of both eyes stained histologically to highlight keratinization and imaged using high-resolution microscopy. A masked investigator digitally delimited and measured the average sagittal width of the lid wiper conjunctiva and mucocutaneous junction using ImageJ. Results: The upper lid wiper conjunctiva measured 424 ± 171 μm, 404 ± 75, 667 ± 219 and 266 ± 64 in asymptomatic soft, symptomatic soft, rigid and non-contact lens wearers, respectively. The corresponding lower lid wiper conjunctivae measured 141 ± 57 μm, 232 ± 150, 519 ± 212 and 225 ± 102, which was significantly narrower than that of the upper eyelid in most cases (p < 0.05). Symptoms were not associated with lid margin changes; however, rigid lens wear and clinical LWE were associated with histologically enlarged lid wiper conjunctival areas and increased keratinization. Conclusion: A novel, exploratory account of histological measures of LWE and cytomorphological change associated with contact lens wear suggests mechanical or frictional cellular insult is occurring at the lid wiper conjunctiva.

Qiao,H., Luensmann,D., Heynen,M., Drolle,E., Subbaraman,L. N., Scales,C., Riederer,D., Fadli,Z., Jones,L. In Vitro Evaluation of the Location of Cholesteryl Ester Deposits on Monthly Replacement Silicone Hydrogel Contact Lens Materials Clinical Ophthalmology 2020;14(September):2821-2828 [ Show Abstract ]

Purpose: The deposition profile of cholesteryl ester on the surface and throughout the matrix of silicone hydrogel contact lens (CL) materials was determined under conditions that mimic a daily wear regimen.

Methods: In this in vitro study, four SiHy CL materials (senofilcon C, lotrafilcon B, comfilcon A and samfilcon A) were incubated in an artificial tear solution (ATS) for up to 30 days. CL incubation was alternated between the ATS (16 hours) and a multipurpose care regimen (8 hours). The ATS included fluorescently tagged cholesteryl ester (5-cholesten-3ß-ol 6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]caproate; CE-NBD) and confocal laser scanning microscopy visualized the distribution of the lipid through the CLs.

Results: The distribution of CE-NBD was homogenous from the anterior to posterior surface in senofilcon C and comfilcon A, at all time points. For lotrafilcon B and samfilcon A, CE-NBD localization was heterogeneous, with greater amounts on the surfaces on Day 1 and Day 14 compared to the lens matrix; however, differences in concentration between the surface and bulk diminished by Day 30.

Conclusion: The distribution of the non-polar lipid CE-NBD varied with lens material chemistry. While some lens materials deposited the lipid primarily on the surface after 16 hours of exposure, all materials exhibited a homogenous distribution after one month.

Keywords: lipid distribution, silicone hydrogel contact lenses, cholesteryl ester, artificial tear solution

Rangarajan,R., Ketelson,H. A., Do,R., McCanna,D. J., Suko,A., Enstone,D., Subbaraman,L., Dantam,J., Jones,L. W. Effect of Artificial Tear Formulations on the Metabolic Activity of Human Corneal Epithelial Cells after Exposure to Desiccation Journal of Visualized Experiments 2020 (159):e60812 [ Show Abstract ]

Artificial lipid-containing tear formulations are developed to reduce tear evaporation by the restoration of a deficient tear lipid layer. Artificial tear formulations that prevent cell desiccation will result in ocular surface protection and the maintenance of cell metabolic activity. During dehydration, cells undergo the process of loss of metabolic activity and subsequently cell death. This work describes a method for assessing the efficacy of artificial tear formulations. The metabolic dye (i.e., alamarBlue) changes from a low fluorescent molecule resazurin to a fluorescent molecule resorufin in viable cells. The biological performance of an artificial tear formulation is measured as the ability of the formulation to (a) maintain cell viability and (b) provide cell protection from desiccation. Growth media and saline are used as controls for the cell viability/desiccation tests. Cells are incubated with test solutions for 30 min and then desiccated for 0 or 5 min at 37 °C and 45% relative humidity. Cell metabolic activity after initial exposure and after cell desiccation is then determined. The results show the comparative effects of eye drop formulations on cell metabolic activity and desiccation protection. This method can be used to test dry eye formulations that are designed to treat individuals with evaporative dry eye.

Shows,A., Redfern,R. L., Sickenberger,W., Fogt,J. S., Schulze,M., Lievens,C., Szcottka-Flynn,L., Schwarz,S., Tichenor,A. A., Marx,S., Lemp-Hull,J. M. Lipid Analysis on Block Copolymer–containing Packaging Solution and Lens Care Regimens: A Randomized Clinical Trial Optometry & Vision Science 2020;97(8):565-572 [ Show Abstract ]

SIGNIFICANCE: Lotrafilcon B lenses packaged in and cared for with block copolymer–containing (polyoxyethylenepolyoxybutylene; EOBO) lens care solutions resulted in lower cholesterol extraction than each of the habitual silicone hydrogel lens/multipurpose solution (MPS) regimens tested.

PURPOSE: This study aimed to compare the extracted cholesterol of lotrafilcon B lenses packaged in and cared for with EOBO-containing lens care solutions with the extracted cholesterol of habitual silicone hydrogel lenses cared for with MPS not containing EOBO.

METHODS: In this prospective, randomized, observer-masked parallel study, habitual wearers of senofilcon C, senofilcon A, comfilcon A, and samfilcon A contact lenses using a non-EOBO MPS were randomized 1:1 to lotrafilcon B lenses packaged in and cared for with EOBO-containing solutions or to their habitual lenses and MPS. Subjects randomized to lotrafilcon B were further randomized to one of two EOBO-containing lens care solutions, OPTI-FREE PUREMOIST or CLEAR CARE PLUS with HydraGlyde (Alcon Laboratories, Inc., Fort Worth, TX). A subset of right eye lenses was collected after wear, and total cholesterol was extracted and measured using a fluorometric enzymatic assay.

RESULTS: Of 143 lenses analyzed, 95 were from subjects randomized to their habitual lenses/MPS and 48 to lotrafilcon B + EOBO lenses plus CLEAR CARE PLUS with HydraGlyde or OPTI-FREE PUREMOIST. The mean amounts of cholesterol extracted from lotrafilcon B + EOBO lenses cared for with CLEAR CARE PLUS with HydraGlyde (0.28 ± 0.18 μ g/lens) and OPTI-FREE PUREMOIST (0.28 ± 0.48 μ g/lens) were significantly lower than those extracted from senofilcon C (4.18 ± 3.25 μ g/lens), senofilcon A (2.19 ± 2.69 μ g/lens), comfilcon A (2.17 ± 1.47 μ g/lens), and samfilcon A (2.07 ± 1.48 μ g/lens) lenses used with MPS (P < .0001 each).

CONCLUSIONS: Cholesterol sorption was significantly lower in wearers of lotrafilcon B lenses cared for with polyoxyethylene-polyoxybutylene–containing lens care solutions than in users of habitual silicone hydrogel lenses cared for with non–polyoxyethylene-polyoxybutylene MPS.

Silverstein,S., Yeu,E., Tauber,J., Guillon,M., Jones,L., Galarreta,D., Srinivasan,S., Manoj,V. Symptom Relief Following a Single Dose of Propylene Glycol-Hydroxypropyl Guar Nanoemulsion in Patients with Dry Eye Disease: A Phase IV, Multicenter Trial Clinical Ophthalmology 2020;14(October):3167-3177 [ Show Abstract ]

Purpose: To evaluate symptom relief in patients with dry eye disease (DED) following a single drop of propylene glycol-hydroxypropyl guar (PG-HPG) nanoemulsion (Systane® Complete) lubricant eye drops.

Methods: This was a Phase IV, multicenter, open-label, interventional study in adult patients with DED of aqueous-deficient, evaporative, and mixed subtypes. Patients instilled one drop of PG-HPG in each eye at Day 1. Endpoints included change from baseline in dry eye symptom and soothing sensation scores on Day 1 at 0, 4, and 8 hours post-dose. Symptom scores were assessed on a 0– 10 scale (0=no symptoms; 10=worst imaginable symptom). Tolerability of the drop was assessed based on assessment score on Day 1 following instillation for overall cohort and by DED subtype.

Results: A total of 134 patients received treatment (mean age: 56.6 years; female: 75.4%). Median changes from baseline at Day 1 in dry eye symptom scores were − 1.0 (95% confidence interval [CI]:-3.0,-1.0), − 2.0 (95% CI:-3.0,-2.0), and − 2.0 (95% CI:-2.0,-1.0) at 0, 4, and 8 hours respectively. Subgroup analysis showed a median change from baseline in dry eye symptom score of − 2 (95% CI:-3.0,-1.0) for aqueous-deficient and evaporative subtypes and − 1 (95% CI:-3.0,-1.0) for mixed subtype at 8 hours. Median soothing sensation scores were 3 at 0 and 4 hours and 3.5 at 8 hours, with a range of 0– 10. Median (range) tolerability assessment scores were 0 (0– 8) for burning sensation, stinging sensation, blurring, and 0 (0– 10) for foreign body sensation. Tolerability assessment scores by DED subtype confirmed that the majority of patients reported scores in the range of 0– 5 for all components and in all subgroups analyzed.

Conclusion: Our study demonstrated that PG-HPG nanoemulsion provided instant/immediate and sustained symptom relief for 8 hours post-single application and was well tolerated in patients with DED, demonstrated by their responses on each of the assessment scales.

Keywords: aqueous-deficient dry eye, dry eye disease, evaporative dry eye, propylene glycol-hydroxypropyl guar nanoemulsion ocular lubricant, mixed dry eye

Tse,J., Rizwan,M., Rasmussen,J., Jones,L., Yim,E. K. F. Gelatin Methacrylate as an Enzyme-Controlled Release Vehicle of Hyaluronic Acid for the Treatment of Recurrent Corneal Erosion Applied Bio Materials 2020;3(9):6214-6223 [ Show Abstract ]

Recurrent corneal erosion (RCE) is a condition where the superficial corneal epithelial cells sporadically shed because of poor attachment to the underlying basement membrane, resulting in pain and discomfort. RCE-afflicted corneas exhibit elevated biological factors and enzymes, such as matrix metalloproteinase (MMP)-9. Soft bandage contact lenses (BCLs) are a commonly recommended treatment as they permit continued vision during recovery. However, they do not outperform alternative treatments as they currently lack active ingredients for ocular surface repair. Development of BCLs with a sustained release of active ingredients to promote RCE wound healing over an extended period of time would be clinically valuable. We fabricated gelatin methacrylate (GelMA) hydrogels with MMP-9-triggered controlled release for further BCL development. GelMA disks were characterized to determine the optimal concentration and methacrylation degree for sustained release in the presence of MMP-9. The chosen active ingredient, 60 kDa hyaluronic acid (HA), was verified to promote wound healing in rabbit corneal epithelial cell and human corneal epithelial cell wound assays. The active ingredient was loaded into GelMA hydrogels, and the bioavailability of the vehicle was determined. The GelMA hydrogels revealed a tunable profile for diffusion and enzyme-mediated controlled release of a model molecule. The 60 kDa HA-loaded GelMA disks showed improvement in wound healing at HA loadings of 150 and 250 μg by improving the wound healing rates by 28% (68.7% wound closure) and 26% (67.9% wound closure), respectively, compared to the control (50.5% wound closure) at 24 h. The HA-loaded GelMA disks with 150 and 250 μg HA also exhibited shortened wound closure time of 75 h compared to >147 h with a bolus daily delivery of HA for wound closure. Overall, we demonstrated that the fabricated GelMA hydrogels offered an enzyme-triggered option as a sustained release material for future RCE treatments.

van der Worp,E., Wolffsohn,J., Jones,L. When was the last time you fitted a soft lens? Cont Lens Anterior Eye 2020;43(5):415-417 [ Show Abstract ]

A recent webinar “discussing the topic of soft lenses, examining dropout rates and putting forward suggestions for how eye care practitioners can ‘get control’ over their fitting” was hosted by the British Contact Lens Association (BCLA). However, the webinar and this editorial addresses much more than merely’ lens fitting’ and ‘dropouts.’ It seems that the profession is almost at a crossroads in which its future is defined by whether the profession stands as contact lens fitters and specialists or whether contact lenses are simply a commodity that can be sold over the internet.

Willcox,M. D. P., Walsh,K. Nichols,J. J., Morgan,P. B., Jones,L. W. The ocular surface, coronaviruses and COVID‐19 Clinical and Experimental Optometry 2020;103(4):418-424 [ Show Abstract ]

The ocular surface has been suggested as a site of infection with Coronavirus‐2 (SARS‐CoV‐2) responsible for the coronavirus disease‐19 (COVID‐19). This review examines the evidence for this hypothesis, and its implications for clinical practice. Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), responsible for the COVID‐19 pandemic, is transmitted by person‐to‐person contact, via airborne droplets, or through contact with contaminated surfaces. SARS‐CoV‐2 binds to angiotensin converting enzyme‐2 (ACE2) to facilitate infection in humans. This review sets out to evaluate evidence for the ocular surface as a route of infection. A literature search in this area was conducted on 15 April 2020 using the Scopus database. In total, 287 results were returned and reviewed. There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface. Evidence from animal studies is limited, with a single study suggesting viral particles on the eye can travel to the lung, resulting in very mild infection. Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID‐19, along with isolated cases of conjunctivitis as a presenting sign. Coronaviruses have been rarely isolated from tears or conjunctival swabs. The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection. Additionally, hypotheses that the virus could travel from the nasopharynx or through the conjunctival capillaries to the ocular surface during infection are probably incorrect. Conjunctivitis and isolation of the virus from the ocular surface occur only rarely, and overwhelmingly in patients with confirmed COVID‐19. Necessary precautions to prevent person‐to‐person transmission should be employed in clinical practice throughout the pandemic, and patients should be reminded to maintain good hygiene practices.

Wolffsohn,J. S., Calossi,A., Cho,P., Gifford,K., Jones,L., Jones,D., Guthrie,S., Li,M., Lipener,C., Logan,N. S., Malet,F., Peixoto-de-Matos,S. C., González-Méijome,J. M., Nichols,J. J., Orr,J. B., Santodomingo-Rubido,J., Schaefer,T., Thite,N., van der Worp,E., Tarutta,E., Iomdina,E., Ali,B. M., Villa-Collar,C., Abesamis-Dichoso,C., Chen,C., Pult,H., Blaser,P., Parra Sandra Johanna,G., Iqbal,F., Ramos,R., Carrillo Orihuela,G., Boychev,N. Global trends in myopia management attitudes and strategies in clinical practice – 2019 Update Cont Lens Anterior Eye 2020;43(1):9-17 [ Show Abstract ]

Purpose: A survey in 2015 identified a high level of eye care practitioner concern about myopia with a reported moderately high level of activity, but the vast majority still prescribed single vision interventions to young myopes. This research aimed to update these findings 4 years later. Methods: A self-administrated, internet-based questionnaire was distributed in eight languages, through professional bodies to eye care practitioners globally. The questions examined: awareness of increasing myopia prevalence, perceived efficacy of available strategies and adoption levels of such strategies, and reasons for not adopting specific strategies. Results: Of the 1336 respondents, concern was highest (9.0 ± 1.6; p < 0.001) in Asia and lowest (7.6 ± 2.2; p < 0.001) in Australasia. Practitioners from Asia also considered their clinical practice of myopia control to be the most active (7.7 ± 2.3; p < 0.001), the North American practitioners being the least active (6.3 ± 2.9; p < 0.001). Orthokeratology was perceived to be the most effective method of myopia control, followed by pharmaceutical approaches and approved myopia control soft contact lenses (p < 0.001). Although significant intra-regional differences existed, overall, most practitioners did not consider single-vision distance under-correction to be an effective strategy for attenuating myopia progression (79.6 %), but prescribed single vision spectacles or contact lenses as the primary mode of correction for myopic patients (63.6 ± 21.8 %). The main justifications for their reluctance to prescribe alternatives to single vision refractive corrections were increased cost (20.6 %) and inadequate information (17.6 %). Conclusions: While practitioner concern about myopia and the reported level of activity have increased over the last 4 years, the vast majority of eye care clinicians still prescribe single vision interventions to young myopes. With recent global consensus evidence-based guidelines having been published, it is hoped that this will inform the practice of myopia management in future.

Xu,M., Sivak,J. G., McCanna,D. J. Ocular toxicology: synergism of UV radiation and benzalkonium chloride
Cutaneous and Ocular Toxicology 2020;39(4):370-379 [ Show Abstract ]

Purpose: To investigate the combined toxic effect of ultraviolet (UV) radiation and benzalkonium chloride (BAK), a common preservative in ophthalmic eye drops, on human corneal epithelial cells (HCEC).

Methods: Cultured HCEC were exposed to different combined and separate UV (280-400 nm) and BAK solutions at relevant human exposure levels. Human exposure to UV can occur before, during, or after eye drop installation, therefore, three different orders of ocular exposures were investigated: UV and BAK at the same time, UV first followed by BAK, and BAK first followed by UV. Control treatments included testing HCEC exposed to BAK alone and also HCEC exposed to UV alone. In addition, phosphate-buffered saline (PBS) was used as a negative control. After exposure, cell metabolic activity of the cultures was measured with PrestoBlue, and cell viability was determined using confocal microscopy with viability dyes.

Results: BAK alone reduced the metabolic activity and cell viability of HCEC in a dose- and time-dependent manner. UV alone at a low dose (0.17 J/cm2) had little toxicity on HCEC and was not significantly different from PBS control. However, UV plus BAK showed combined effects that were either greater than (synergistic) or equal to (additive) the sum of their individual effects. The synergistic effects occurred between low dose UV radiation (0.17 J/cm2) and low concentrations of BAK (0.001%, 0.002%, 0.003%, and 0.004%).

Conclusions: This investigation determined that at relevant human exposure levels, the combination of UV radiation (280-400 nm) and BAK can cause synergistic and additive toxic effects on human corneal epithelial cells. This finding highlights the importance of considering the combined ocular toxicity of BAK and solar radiation in the risk assessment of BAK-preserved ophthalmic solutions.

Yeu,E., Silverstein,S., Guillon,M., Schulze,M., Galaretta,D., Srinivasan,S., Manoj,V. Efficacy and Safety of Phospholipid Nanoemulsion-Based Ocular Lubricant for the Management of Various Subtypes of Dry Eye Disease: A Phase IV, Multicenter Trial Clinical Ophthalmology 2020;14:2561-2570 [ Show Abstract ]

Purpose: To evaluate the clinical efficacy and safety of propylene glycol/hydroxypropylguar (PG-HPG)-based nanoemulsion (Systane ® Complete) lubricant eye drops in participants with dry eye disease (DED).

Participants and Methods: In this phase IV, open-label, single-arm, interventional, multicenter study, adult participants with DED – subtyped into aqueous deficient, evaporative, and mixed dry eye – were instructed to instill one drop of PG-HPG in each eye twice a day for 28 days. Endpoints included change from baseline in tear film break-up time (TFBUT) (primary) and ocular discomfort visual analog scale (VAS) score at Day 14 and TFBUT at Day 28 (secondary). Safety was assessed throughout the study. Data were analyzed for overall patient cohort and by DED subtypes. Results: A total of 134 participants received treatment (mean age: 56.6 years; female: 75.4%). At Day 14, the mean (standard deviation [SD]) TFBUT increased from 2.6 (1.00) seconds at baseline to 4.2 (2.92) seconds (mean change: 1.5 [2.80] seconds); median change was 0.8 seconds (95% CI: 0.52, 1.19) for the overall cohort; the change was maintained at Day 28 (mean change: 1.4 (2.80) seconds, median change: 0.8 seconds (95% CI: 0.49, 1.17). Subgroup analysis showed a mean change (SD) from baseline in TFBUT of 1.1 (2.41) seconds for aqueous deficient, 2.4 (3.17) seconds for evaporative, and 1.2 (2.63) seconds for mixed dry eye at Day 14, respectively. The ocular discomfort VAS score improved (decreased) from baseline at Day 14 (mean [SD] change: −17.3 [24.80]) for the overall cohort, −22.0 [21.73] for aqueous deficient, −17.6 [24.17] for evaporative and −13.1 [27.49] for mixed dry eye subgroups). Adverse events (AEs) were reported in 9 (6.7%) participants. No serious AEs were reported during the study.

Conclusion: Our study findings demonstrated that PG-HPG-based nanoemulsion lubricant eye drops were effective and well tolerated in participants with DED and all of its subtypes. Keywords: aqueous deficient dry eye, dry eye disease, evaporative dry eye, propylene glycol/hydroxypropyl guar-nanoemulsion ocular lubricant, mixed dry eye

2019

Bitton,E., Ngo,W., Dupont,P. Eyelid hygiene products: A scoping review Cont Lens Anterior Eye 2019;42(6):591-597

Chamberlain,P., Gonzalez-Meijome,J., Ngo,C., Jones,D., Young,G. A three-year randomised clinical trial of MiSight lenses for myopia control Optometry & Vision Science 2019;96(8):556-567 [ Show Abstract ]

SIGNIFICANCE: Results of this randomized, double-masked clinical trial demonstrate the effectiveness of the MiSight soft contact lens in slowing myopia progression over multiple years.

PURPOSE: The purpose of this study was to quantify the effectiveness of MiSight daily disposable soft contact lens in slowing the progression of juvenile-onset myopia.

METHODS: Myopic children (spherical equivalent refraction, -0.75 to -4.00 D; astigmatism, <1.00 D) aged 8 to 12 years with no prior contact lens experience were enrolled in a 3-year, double-masked, randomized clinical trial at four investigational sites in four countries. Subjects in each group were matched for age, sex, and ethnicity and were randomized to either a MiSight 1-day contact lens (test) or Proclear 1-day (control; omafilcon A) and worn on a daily disposable basis. Primary outcome measures were the change in cycloplegic spherical equivalent refraction and axial length.

RESULTS: Of the subjects enrolled, 75.5% (109/144) completed the clinical trial (53 test, 56 control). Unadjusted change in spherical equivalent refraction was -0.73 D (59%) less in the test group than in the control group (-0.51 ± 0.64 vs. -1.24 ± 0.61 D, P < .001). Mean change in axial length was 0.32 mm (52%) less in the test group than in the control group (0.30 ± 0.27 vs. 0.62 ± 0.30 mm, P < .001). Changes in spherical equivalent refraction and axial length were highly correlated (r = -0.90, P < .001). Over the course of the study, there were no cases of serious ocular adverse events reported. Four asymptomatic corneal infiltrative (one test, three control) events were observed at scheduled study visits.

CONCLUSIONS: Results of this clinical trial demonstrate the effectiveness of the MiSight daily disposable soft contact lens in slowing change in spherical equivalent refraction and axial length.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01729208.

Fonn,D., Jones,L. Hand hygiene is linked to microbial keratitis and corneal inflammatory events Cont Lens Anterior Eye 2019;42(2):132-135 [ Show Abstract ]

Lack of or inadequate hand washing is a risk factor in the development of contact lens related microbial keratitis and corneal inflammatory events. In the public health domain there is compelling evidence that proper hand washing with soap can save lives. The purpose of this review is to draw attention to some of the public health literature in support of hand washing and how education can influence patients’ hand hygiene behavior. Contact lens wearers are also guilty of poor hand washing behavior but there is scant evidence that education of hand washing procedures of lens wearers alters patient non-compliance. It is well known that pathogenic microbial contamination of contact lenses, lens cases, care solutions and anterior ocular components have been found with contact lens wear. However while the originating source may be hands or water, it is most likely both of these. Besides proper hand washing this paper will include mitigating strategies for avoiding microbial contamination.

Holland,E. J., Darvish,M., Nichols,K. K., Jones,L., Karpecki,P. M. Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review Ocul Surf 2019;17:412-423 [ Show Abstract ]

Dry eye disease (DED) is a multifactorial and complex disease of the ocular surface, with a high prevalence in adults. We systematically reviewed efficacy and safety data from published articles reporting results from prospective, controlled trials of topical ophthalmic drugs for DED. PubMed was searched from January 1997 to October 2017. Twenty-six unique trials investigating 13 ophthalmic drugs were identified, including trials of the approved drugs cyclosporine A, cyclosporine A cationic emulsion, diquafosol, rebamipide and lifitegrast. All identified studies provided level 1 evidence. None of the large (N > 100) studies demonstrated statistical significance of primary endpoints for both a sign and a symptom endpoint versus a control treatment in the same published trial. Publications on lifitegrast reported statistical superiority in a symptom or sign endpoint versus the control group in a large (N > 200), multicenter trial, with results repeated in trials of similar design. The most common adverse events associated with the approved drugs related to ocular discomfort upon instillation, especially burning/stinging and ocular irritation. The trial design and endpoints used across the studies varied considerably, highlighting the importance of standardization in clinical trials for DED. Recent advances in drug delivery and improved understanding of DED should contribute to new ophthalmic drug approvals.

Jones,L., Drobe,B., González-Méijome,J. M., Gray,L., Kratzer,T., Newman,S., Nichols,J.J., Ohlendorf,A., Ramdass,S., Santodomingo-Rubido,J., Schmid,K. L., Tan,D., Tan,K. O., Vera-Diaz,F. A., Wong,Y. L., Gifford,K. L., Resnikoff,S. IMI - Industry Guidelines and Ethical Considerations for Myopia Control Report Invest Ophthalmol Vis Sci 2019;60(3):M161-M183 [ Show Abstract ]

PURPOSE:
To discuss guidelines and ethical considerations associated with the development and prescription of treatments intended for myopia control (MC).

METHODS:
Critical review of published papers and guidance documents was undertaken, with a view to carefully considering the ethical standards associated with the investigation, development, registration, marketing, prescription, and use of MC treatments.

RESULTS:
The roles and responsibilities of regulatory bodies, manufacturers, academics, eye care practitioners, and patients in the use of MC treatments are explored. Particular attention is given to the ethical considerations for deciding whether to implement a MC strategy and how to implement this within a clinical trial or practice setting. Finally, the responsibilities in marketing, support, and education required to transfer required knowledge and skills to eye care practitioners and academics are discussed.

CONCLUSIONS:
Undertaking MC treatment in minors creates an ethical challenge for a wide variety of stakeholders. Regulatory bodies, manufacturers, academics, and clinicians all share an ethical responsibility to ensure that the products used for MC are safe and efficacious and that patients understand the benefits and potential risks of such products. This International Myopia Institute report highlights these ethical challenges and provides stakeholders with recommendations and guidelines in the development, financial support, prescribing, and advertising of such treatments.

Korogiannaki,M., Jones,L. W., Sheardown, H. The impact of a hyaluronic acid-grafted layer on the surface properties of model silicone hydrogel contact lenses Langmuir 2019;35(4):950-961 [ Show Abstract ]

The introduction of high oxygen transmissibility silicone hydrogel lenses ameliorated hypoxia-related complications, making them the most prescribed type of contact lens. Despite the progress made over the last two decades to improve their clinical performance, symptoms of ocular dryness and discomfort and a variety of adverse clinical events are still reported. Consequently, the rate of contact lens wear discontinuation has not been appreciably diminished by their introduction. Aiming to improve the interfacial interactions of silicone hydrogel contact lenses with the ocular surface, a biomimetic layer of the hydrophilic glycosaminoglycan hyaluronic acid (HA) (100 kDa), was covalently attached to the surface of model poly(2-hydroxyethyl methacrylate-co-3-methacryloxypropyl-tris-(trimethylsiloxy)silane) (pHEMA-co-TRIS) silicone hydrogel materials via UV-induced thiol-ene "click" chemistry. The surface structural changes after each modification step were studied by FTIR-ATR and XPS. Successful grafting of a homogenous HA layer to the surface of the model silicone hydrogels was confirmed by the consistent appearance of N (1s) and the significant decrease of the Si (2p) peaks, as determined by the low-resolution angle-resolved XPS. The HA-grafted surfaces demonstrated reduced contact angles, dehydration rate and nonspecific deposition of lysozyme and albumin, while maintaining their optical transparency (>90%). In vitro studies demonstrated that the HA-grafted pHEMA-co-TRIS materials did not show any toxicity to human corneal epithelial cells. These results suggest that surface immobilization of HA via thiol-ene "click" chemistry can be used as a promising surface treatment for silicone hydrogel contact lenses.

Moezzi,A. M., Varikooty,J., Luensmann,D., Schulze,M., Ng,A. Y., Karkkainen,T., Xu,J., Jones,L. The short-term physiological impact of switching reusable silicone hydrogel wearers into a hydrogel daily disposable multifocal Clinical Ophthalmology 2019;13:1193-1202 [ Show Abstract ]

Purpose: To evaluate ocular physiological responses to etafilcon A multifocal (etMF) daily disposable (DD) lenses after 4 weeks of wear, when switching from habitual silicone hydrogel (SiHy) daily wear.
Method: A single-arm, open-label, bilateral dispensing study was conducted in 39 habitual spherical SiHy wearers (14 hyperopes; 25 myopes). Clinical visits occurred with habitual SiHy (control) at baseline and after 4 weeks of etMF DD open-eye lens wear at exit. Objective limbal/bulbar hyperemia using the Oculus K5M (0–4) and subjective grading of lid wiper epitheliopathy (LWE) (0–4) were tested for non-inferiority (NI), using a margin of 1 grade. Corneal thickness along a 10 mm cord was measured using the Visante OCT and tested for NI using a 30 μm margin. Corneal staining area was graded (0–100%).
Results: The least-square mean differences (LSMD) and 95% confidence interval (95% CI) between etMF DD and habitual SiHy in central and peripheral corneal thickness (μm) were 3.64 (−2.0, 9.29) and 3.0 (−7.72, 13.72) in hyperopic, and 3.56 (−0.66, 7.78) and 6.40 (−1.62, 14.42) in myopic subjects. The LSMD (95% CI) for bulbar and limbal hyperemia were −0.08 (−0.19, 0.02) and −0.01 (−0.12, 0.09) in hyperopes, and 0.04 (−0.03, 0.12) and 0.04 (−0.04, 0.11) in myopes. The LSMD (95% CI) for LWE were 0.11 (−0.39, 0.60) and 0.30 (−0.07, 0.67) for hyperopes and myopes, respectively.
Conclusions: No clinically significant differences in a variety of physiological responses were found when habitual reusable SiHy daily wear subjects were refitted into hydrogel etMF, when the subjects were followed for 4 weeks.

Ngo,W., Srinivasan,S., Jones,L. An Eyelid Warming Device for the Management of Meibomian Gland Dysfunction J Optom 2019;12(2):120-130 [ Show Abstract ]

PURPOSE: To determine the effectiveness of the MGDRx EyeBag in managing meibomian gland dysfunction.

METHODS: This was a prospective, randomized, controlled, observer-masked, bilateral eye study that enrolled 29 participants. Participants were randomized into either the EyeBag group or the control group. The EyeBag group used the EyeBag 10minutes 2x/day, and the control group remained on their own dry eye treatment regimen (if applicable). All participants were observed at baseline, 2 weeks (2wk) and 4 weeks (4wk). At 4wk, participants in the EyeBag group were asked to stop using the EyeBag. All participants were seen again at 8 weeks (8wk). Primary outcomes were the Ocular Surface Disease Index (OSDI), Current Symptoms Questionnaire (CSQ), meibomian gland score (MG score), and non-invasive tear breakup time (NIBUT).

RESULTS: Twenty-five participants completed the study (mean age 38±15 years, 7 male). There was a significant change in OSDI over time for the EyeBag group (mean[lower 95% CI, upper 95% CI], baseline: 39.1[31.1,47.0], 2wk: 26.8[19.7,33.9], 4wk: 26.6[16.5,36.7], 8wk: 27.7[18.4,37.0]; p=0.01), but not in the control group (p=0.22), but no significant difference between groups at all time points (all p>0.27). Symptoms immediately improved after conducting the EyeBag based on at-home CSQ scores (Δ=-5.0 points, p<0.01), but not in the control group. For both groups, there was no significant change (p-value EyeBag,p-value control) in MG score (0.21,0.17) and NIBUT (0.49,0.06) over time.

CONCLUSIONS: The EyeBag may relieve symptoms of dry eye, but the effect on meibomian gland function and tear stability when used for only 4 weeks was undetectable.

Nichols,J. J., Chalmers,R. L., Dumbleton,K., Jones,L., Lievens,C. W., Merchea,M. M., Szczotka-Flynn,L. The Case for Using Hydrogen Peroxide Contact Lens Care Solutions: A Review Eye & Contact Lens 2019;45(2):69-82 [ Show Abstract ]

Despite their established disinfection and safety benefits, the use of hydrogen peroxide (H2O2) lens care systems among today's wearers of reusable contact lenses remains low in comparison with multipurpose solution (MPS) use. Multipurpose solution systems, however, present several potential drawbacks that may impact patient outcomes, including the use of chemical preservatives for disinfection, biocompatibility issues, and challenges with respect to lens care compliance. Given their unique composition and mechanism of action, one-step H2O2 systems offer the opportunity to avoid many of the challenges associated with MPS use. This article reviews the evolution of H2O2 lens care systems and examines the current scientific and clinical evidence regarding the relative ease of use, lens and tissue compatibility, disinfection efficacy, and ocular surface safety of H2O2 systems. Evaluation of the available data indicates that in comparison with MPS, one-step H2O2 systems tend to promote more favorable compliance, efficacy, comfort, and ocular surface outcomes for a wide range of contact lens–wearing patients. Based on the current published evidence, the authors recommend that eye care practitioners consider making one-step H2O2 systems their first-line contact lens care recommendation for most wearers of reusable lenses.

Phan,C. M., Subbaraman,L., Jones,L. Uptake and release of polyvinyl alcohol from hydrogel daily disposable contact lenses Optom Vis Sci 2019;96(3):180-186 [ Show Abstract ]

SIGNIFICANCE:
Polyvinyl alcohol is a wetting agent that could reduce the symptoms of dry eye and contact lens discomfort. Currently, only one lens type, nelfilcon A (DAILIES AquaComfort Plus), releases polyvinyl alcohol. The concept of releasing this agent from contact lenses could be applied to other lens materials.

PURPOSE:
The purpose of this study was to measure the release of polyvinyl alcohol from commercially available hydrogel daily disposable contact lenses using refractive index and iodine-borate methods.

METHODS:
Etafilcon A, omafilcon A, and nelfilcon A were soaked in phosphate-buffered saline and 0.2% trifluoroacetic acid/acetonitile for 24 hours to remove residual blister pack components. The lenses were then incubated in a 10-mg/mL solution of polyvinyl alcohol for 24 hours. After the incubation period, the lenses were placed in 2 mL of phosphate-buffered saline. At specified time intervals, t = 0.5, 1, 2, 4, 8, 12, and 24 hours, the samples were evaluated using refractive index and an iodine-borate assay. Polyvinyl alcohol uptake was determined by extracting the lenses with methanol for 24 hours.

RESULTS:
There were no differences in the uptake of polyvinyl alcohol between lens types (P > .05). The release of this wetting agent for all lens types followed a burst-plateau profile after the first 30 minutes (P > .05). Nelfilcon A had a slightly higher release of polyvinyl alcohol (P .05).

CONCLUSIONS:
The results suggest that the contact lenses tested in this study have similar efficiency in delivering polyvinyl alcohol.

Phan,C. M., Walther,H., Qiao,H., Shinde,R., Jones,L. Development of an eye model with a physiological blink mechanism Translational Vision Science & Technology 2019;8(5):Article 1 [ Show Abstract ]

Purpose: To develop an eye model with a physiological blink mechanism.

Methods: All parts of the eye model were designed using computer-aided design software. The eyelid consisted of a unique 3D printed structure containing teeth to physically secure a flexible membrane. Both the eyeball and eyelid membrane were synthesized using polyvinyl alcohol (PVA). Four molecular weights of PVA (89–98, 85–124, 130, and 146–186 kDa) were tested at a range of concentrations between 5% and 30% weight/volume. The wettability and water content of these materials were compared with the bovine cornea and sclera. The model was connected to a microfluidic pump, which delivers artificial tear solution (ATS) to the eyelid. A corneal topographer was used to evaluate the tear break-up and tear film regeneration.

Results: The eyelid flexes and slides across the eyeball during each blink, which ensures direct contact between the two surfaces. When loaded with an ATS, this mechanism evenly spreads the solution over the eyeball to generate an artificial tear film. The artificial tear film in this eye model had a tear break-up time (TBUT) of 5.13 ± 0.09 seconds at 1.4 μL/min flow rate, 6 blinks/min, and <25% humidity.

Conclusions: This model simulates a physiological blink actuation and an artificial tear film layer. Future studies will examine variations in flow rates and ATS composition to simulate clinical values of TBUT.

Translational Relevance: The eye model could be used to study in vitro TBUT, tear deposition, and simple drug delivery.

Phan,C. M., Walther,H., Riederer,D., Lau,C., Lorentz,H., Subbaraman,L., Jones,L. Analysis of polyvinyl alcohol release from commercially available daily disposable contact lenses using an in vitro eye model J Biomed Mater Res B Appl Biomater 2019;107(5):1662-1668 [ Show Abstract ]

The purpose of this work was to determine the release of polyvinyl alcohol (PVA) from etafilcon A, omafilcon A, and nelfilcon A daily disposable hydrogel contact lenses using a novel in vitro model. PVA is an ocular lubricant that can be found in multiple formulations of artificial tears. Nelfilcon A innately contains PVA, so only the release of PVA from this lens was evaluated. Etafilcon A and omafilcon A lenses were incubated in a PBS solution containing PVA. The release of PVA was evaluated using a novel in vitro blink platform with Milli-Q water and PBS under various blink conditions and flow rates. Nelfilcon A lenses significantly released more PVA than other lenses at 0.5 and 1.5 h in both PBS and Milli-Q water (p 0.05). All tested groups and lenses showed a burst release within the first 4.5 h and rapidly plateaued thereafter. The current study demonstrates that releasable PVA (whether through uptake or through being inherently available from the material) is loosely bound on hydrogel lenses, and the majority is released within 4.5 h.

Pucker,A. D., Jones-Jordan, L.A., Marx,S., Powell,D. R., Kwan,J. T., Srinivasan,S., Sickenberger,W., Jones,L., The role of soft contact lens wear on meibomian gland morphology and function Eye & Contact Lens 2019;45(4):276-277 [ Show Abstract ]

The impact of a contact lens on the eye has long been of interest to practitioners who prescribe contact lenses and to the patients who wear them. One particular area of concern within the past several years has been related to how a contact lens may impact the meibomian glands (MGs) because changes in MG structure and/or function have the potential to impact the overall integrity of the ocular surface and contact lens success. Ucakhan and Arslanturk-Eren's recent manuscript published in Eye & Contact Lens has attempted to expand our knowledge of this topic by studying a group of contact lens–wearing and non–contact lens–wearing subjects and seeking to understand how the use of silicone hydrogel contact lenses may impact MG health. Their study overall concluded that “soft CL wear causes significant morphological and functional changes in MG with thickening of MG presenting an early diagnostic finding of MG dysfunction on meibography.”

Pucker,A. D., Jones-Jordan, L.A., Marx,S., Powell,D. R., Kwan,J. T., Srinivasan,S., Sickenberger,W., Jones,L., Contact Lens Assessment of Symptomatic Subjects (CLASS) Study Group Clinical factors associated with contact lens dropout Cont Lens Anterior Eye 2019;42(3):318-324 [ Show Abstract ]

PURPOSE: Contact lens (CL) dropout is estimated to be approximately equal to the number of new wearers per year, resulting in virtually no growth in the global CL market. The purpose of this study was to determine ocular and CL factors associated with CL dropout.

METHODS: This five-site study recruited subjects 18-45 years of age who had ceased CL wear within the past 6-12 months due to discomfort. Dropout subjects were compared to age- and sex-matched currently successful CL wearers. Each subject was administered a symptoms survey and a study-specific survey that queried general CL history and compliance. Clinical testing included non-invasive tear break-up time, tear meniscus height, blepharitis assessment, meibum quality and expression, and meibography.

RESULTS: A total of 56 matched-pairs were recruited. Dry eye was found to significantly increase a subject's odds of dropping out of CLs. The odds of dropping out of CLs was also significantly increased with each worsening grade of upper or lower eyelid meibomian gland (MG) plugging, upper eyelid meibum quality, and upper eyelid MG tortuosity. No other factors analyzed increased a subject's odds of dropping out of CLs.

CONCLUSIONS: CL dropout may be precipitated by underlying dry eye symptoms, though most dry eye signs, with the exception of MG structure and function, had minimal predictive value for CL dropout. Nevertheless, evidence suggests that practitioners should screen for and educate CL patients about the importance of maintaining healthy MGs, which may potentially allow them to maintain comfortable CL use and increase their CL longevity.

Pucker,A. D., Jones-Jordan,L. A., Kunnen,C. M. E., Marx,S., Powell,D. R., Kwan,J. T., Srinivasan,S., Sickenberger,W., Jones,L. Impact of meibomian gland width on successful contact lens use Cont Lens Anterior Eye 2019;42(6):646-651 [ Show Abstract ]

Purpose: To evaluate meibomian gland (MG) width and determine its impact on successful contact lens (CL) use and ocular health.
Methods: A five-site study was conducted by recruiting 18- to 45-year-old subjects who had dropped out of CLs because of discomfort. CL dropouts were compared to age- and sex-matched successful CL wearers. Right eyes were evaluated for tear break-up time, tear meniscus height, MG expressibility, meibum quality, and meibography. Central MG widths were evaluated with a custom MATLAB program.
Results: CL dropouts (n = 56) and successful CL (n = 56) wearers had similar grades for upper (p = 1.0) and lower (p = 0.22) MG atrophy, upper (p = 0.07) and lower (p = 0.89) MG tortuosity, and upper (p = 0.92) and lower (p = 0.97) MG widths. Upper eyelid MG widths were narrower than lower eyelid MG widths (p = 0.03). Upper and lower MG tortuosity (p < 0.001) and widths (p = 0.03) were associated, but not atrophy (p = 0.42). Lower eyelid MG widths were associated with MG expressibility (p = 0.01), but MG widths were not with any other factors.
Conclusions: Successful CL wear does not appear to be clinically influenced by MG width or other measures of MG structural integrity. Lower eyelid MGs were wider than upper eyelid MGs and narrower lower eyelid MGs were associated with worse MG expressibility, suggesting that narrower MGs may produce abnormal meibum. Data also suggests that MG factors of both eyelids should be evaluated in practice.

Troilo,D., Smith,E. L. 3rd, Nickla,D. L., Ashby,R., Tkatchenko,A. V., Ostrin,L. A., Gawne,T. J., Pardue,M. T., Summers,J. A., Kee,C. S., Schroedl,F., Wahl,S., Jones,L. IMI - Report on Experimental Models of Emmetropization and Myopia Invest Ophthalmol Vis Sci 2019;60(3):M31-M88 [ Show Abstract ]

The results of many studies in a variety of species have significantly advanced our understanding of the role of visual experience and the mechanisms of postnatal eye growth, and the development of myopia. This paper surveys and reviews the major contributions that experimental studies using animal models have made to our thinking about emmetropization and development of myopia. These studies established important concepts informing our knowledge of the visual regulation of eye growth and refractive development and have transformed treatment strategies for myopia. Several major findings have come from studies of experimental animal models. These include the eye's ability to detect the sign of retinal defocus and undergo compensatory growth, the local retinal control of eye growth, regulatory changes in choroidal thickness, and the identification of components in the biochemistry of eye growth leading to the characterization of signal cascades regulating eye growth and refractive state. Several of these findings provided the proofs of concepts that form the scientific basis of new and effective clinical treatments for controlling myopia progression in humans. Experimental animal models continue to provide new insights into the cellular and molecular mechanisms of eye growth control, including the identification of potential new targets for drug development and future treatments needed to stem the increasing prevalence of myopia and the vision-threatening conditions associated with this disease.

Walsh,K., Jones,L. The use of preservatives in dry eye drops Clinical Ophthalmology 2019;13:1409-1425 [ Show Abstract ]

Topical ocular preparations are widely recommended by health care professionals, or chosen by patients, to help manage dry eye disease (DED). The chronic and progressive nature of DED may result in the administration of topical products several times a day, over a period of many years. Given DED is a condition that by definition affects the ocular surface, it is important to understand how the repeated use of eye drops may impact the ocular surface, influence clinical signs, affect symptoms, and impact the overall disease process of dry eye. The component in topical preparations with the greatest potential to adversely affect the ocular surface is the preservative. This paper reviews the literature in relation to the use of preservatives in formulations for dry eye. The ocular effects of benzalkonium chloride (BAK) are summarised and compared to the performance of alternative preservatives and preservative-free formulations. Use of preserved and preservative-free drops in relation to the management of varying stages of DED is discussed.

Walther,H., Subbaraman,L, N., Jones,L. Efficacy of Contact Lens Care Solutions in Removing Cholesterol Deposits From Silicone Hydrogel Contact Lenses. Eye & Contact Lens 2019;45(2):105-111 [ Show Abstract ]

PURPOSE: To determine the efficacy of multipurpose solutions (MPSs) on the removal of cholesterol deposits from silicone hydrogel (SH) contact lens materials using an in vitro model.
MATERIALS AND METHODS: Five SH lens materials: senofilcon A, comfilcon A, balafilcon A, lotrafilcon A, and lotrafilcon B were removed from the blister pack (n=4 for each lens type), incubated for 7 days at 37°C in an artificial tear solution containing C radiolabeled cholesterol. Thereafter, lenses were stored in a preserved saline solution control (Sensitive Eyes Saline Plus) or cleaned with 1 of the 5 MPSs incorporating different preservatives (POLYQUAD/ALDOX, polyquaternium-1/alexidine, polyquaternium-1/PHMB, and 2 based on PHMB alone) using a rub and rinse technique, according to the manufacturer's recommendations, and stored in the MPS for a minimum of 6 hr. Lenses were then extracted with 2:1 chloroform:methanol, analyzed in a beta counter, and μg/lens of cholesterol was determined.
RESULTS: Balafilcon A and senofilcon A lens materials showed the highest amounts of accumulated cholesterol (0.93±0.02 μg/lens; 0.95±0.01 μg/lens, respectively), whereas lotrafilcon A and lotrafilcon B deposited the lowest amounts (0.37±0.03 μg/lens; 0.47±0.12 μg/lens, respectively). For all lens materials, the MPS preserved with POLYQUAD/ALDOX removed more deposited cholesterol than any other test solution; however, the amount of removed cholesterol contamination from the individual contact lenses was only statistically significant for balafilcon A and senofilcon A (P=0.006 and P=0.042, respectively). Sensitive eyes and the other evaluated MPSs showed no significant effect on cholesterol removal (P>0.05).
CONCLUSION: Cholesterol-removal efficacy varies depending on the combination of lens material and solution. Only 1 MPS showed a statistically significant reduction of cholesterol deposit for only 2 of the 5 tested lens materials.

Walther,H., Subbaraman,L. N., Jones,L. Novel in vitro method to determine pre-lens tear break-up time of hydrogel and silicone hydrogel contact lenses Cont Lens Anterior Eye 2019;42(2):178-184 [ Show Abstract ]

PURPOSE:
To develop an in vitro model to determine pre-lens non-invasive break-up time (NIBUT) and to subsequently use this method to compare the NIBUT over contemporary daily disposable (DD) contact lenses (CL).
METHODS:
Three silicone hydrogel (SH) and two conventional hydrogel (CH) DD CLs were incubated in an artificial tear solution (ATS). A model blink cell (MBC) was utilised to mimic intermittent air exposure. CLs were repeatedly submerged for 3 seconds (s) and exposed to air for 10 s over periods of 2, 6, 12, and 16 hours (h). NIBUTs (n = 4) were determined out of the blister pack (T0) and at the end of each incubation period.
RESULTS:
Overall, nesofilcon A showed the longest NIBUTs (p < 0.001). At T0, CHs revealed significantly longer NIBUTs (p ≤ 0.001) than SHs. After 2 h, nesofilcon A showed the longest NIBUT, however, this was only statistically significant compared with delefilcon A (p ≤ 0.001). After 6 h, nesofilcon A NIBUT was significantly longer than all other CLs (p ≤ 0.001). Etafilcon A showed a significantly longer NIBUT (p ≤ 0.001) after 12 h and delefilcon A had the longest NIBUT (p ≤ 0.001) after 16 h. Statistically significant (p ≤ 0.05) changes of NIBUT within the lens materials varied between time points. After 16 h, all CLs showed significant reductions in NIBUTs (p ≤ 0.001) in comparison to T0.
CONCLUSION:
NIBUT values reduced gradually over time and varying levels of deposition impacted measured pre-lens NIBUTs. While NIBUT of CH materials are longer immediately out of the blister pack, after tear film exposure, the NIBUTs obtained using this methodology became very similar.

Wolffsohn,J. S., Flitcroft,D. I., Gifford,K. L., Jong,M., Jones,L., Klaver,C. C. W., Logan,N. S., Naidoo,K., Resnikoff,S., Sankaridurg,P., Smith,E. L. 3rd, Troilo,D., Wildsoet,C. F. IMI - Myopia Control Reports Overview and Introduction Invest Ophthalmol Vis Sci 2019;60(3):M1-M19 [ Show Abstract ]

With the growing prevalence of myopia, already at epidemic levels in some countries, there is an urgent need for new management approaches. However, with the increasing number of research publications on the topic of myopia control, there is also a clear necessity for agreement and guidance on key issues, including on how myopia should be defined and how interventions, validated by well-conducted clinical trials, should be appropriately and ethically applied. The International Myopia Institute (IMI) reports the critical review and synthesis of the research evidence to date, from animal models, genetics, clinical studies, and randomized controlled trials, by more than 85 multidisciplinary experts in the field, as the basis for the recommendations contained therein. As background to the need for myopia control, the risk factors for myopia onset and progression are reviewed. The seven generated reports are summarized: (1) Defining and Classifying Myopia, (2) Experimental Models of Emmetropization and Myopia, (3) Myopia Genetics, (4) Interventions for Myopia Onset and Progression, (5) Clinical Myopia Control Trials and Instrumentation, (6) Industry Guidelines and Ethical Considerations for Myopia Control, and (7) Clinical Myopia Management Guidelines.

Wolffsohn,J. S., Kollbaum,P. S., Berntsen,D. A., Atchison,D. A., Benavente,A., Bradley,A., Buckhurst,H., Collins,M., Fujikado,T., Hiraoka,T., Hirota,M., Jones,D., Logan,N. S., Lundström,L., Torii,H., Read,S. A., Naidoo,K. IMI - Clinical Myopia Control Trials and Instrumentation Report Invest Ophthalmol Vis Sci 2019;60(3):M132-M160 [ Show Abstract ]

The evidence-basis based on existing myopia control trials along with the supporting academic literature were reviewed; this informed recommendations on the outcomes suggested from clinical trials aimed at slowing myopia progression to show the effectiveness of treatments and the impact on patients. These outcomes were classified as primary (refractive error and/or axial length), secondary (patient reported outcomes and treatment compliance), and exploratory (peripheral refraction, accommodative changes, ocular alignment, pupil size, outdoor activity/lighting levels, anterior and posterior segment imaging, and tissue biomechanics). The currently available instrumentation, which the literature has shown to best achieve the primary and secondary outcomes, was reviewed and critiqued. Issues relating to study design and patient selection were also identified. These findings and consensus from the International Myopia Institute members led to final recommendations to inform future instrumentation development and to guide clinical trial protocols.

Wong,S., Srinivasan,S., Murphy,P. J., Jones,L. Comparison of meibomian gland dropout using two infrared imaging devices Cont Lens Anterior Eye 2019;42(3):311-317 [ Show Abstract ]

Purpose: To measure the degree of meibomian gland (MG) dropout in the lower eyelid determined by analysis of images obtained from the LipiView II (LVII) and the Keratograph 5M (K5M).

Methods: The inferior eyelid of each participant was imaged in a random order using both devices. All images were subjectively assessed by a single-masked investigator to determine the extent of MG loss using the Arita 4-point meiboscore grading scale. The images were also semi-objectively analyzed with ImageJ to calculate the percentage of MG dropout, by tracing around the non-glandular area and the total exposed area of the lower lid.

Results: Twenty participants (mean age 37 years, range 23–60, 60% female) completed the study. A significant difference in meiboscore (mean ± SD) was obtained between the LVII and the K5M (1.43 ± 0.78 vs. 1.90 ± 0.81, Z = 3.25, p = 0.001). The meiboscore 95% limit of agreement (LOA) ranged from −1.88 to +0.93. A significant difference was found with mean ImageJ percentage dropout between the LVII and the K5M (31.5% vs 43.4%, t = −4.8, p = 0.00003). The percentage dropout 95% LOA ranged from −42.79% to +19.06%.

Conclusions: LVII images had significantly lower meiboscores and less percentage MG dropout. Varying amounts of dropout were observed between the devices due the amount of eyelid that was typically everted and because of differences in image quality. These results indicate that these devices should not be used interchangeably to evaluate MG dropout.

Woods,J., Hutchings,N., Srinivasan,S., Jones,L. Geographic distribution of corneal staining in symptomatic dry eye Ocul Surf 2019;18(2):258-266 [ Show Abstract ]

Purpose
To describe the geographic distribution of corneal fluorescein staining across the five corneal zones, among non contact lens wearers who report symptoms of dry eye and determine which corneal zone most frequently exhibited the worst staining.

Methods
Prior studies conducted at the Centre for Ocular Research & Education, Canada, were reviewed for inclusion in the analysis. Each study assessed dry eye symptoms using OSDI and also assessed corneal fluorescein staining in five corneal zones. For each subject, the corneal zones were ranked 1–5 according to their relative staining grade, Rank-1 representing the highest grade.

Results
Data from 13 studies and 368 subjects were included. The total number of zones assigned Rank-1 (worst) staining was 449 (across 264 subjects). The inferior zone had the most Rank-1 counts of all zones at 193/43%, which involved 52.5% of all subjects. The nasal zone had 77/17% involving 20.9% of subjects, followed by the temporal (69/15.5%, 18.8% subjects) and superior zones (63/14%, 17.1% subjects). The central zone had the lowest count of Rank-1 designations, at only 47/10.5%, involving 12.8% of subjects. Bayesian analysis was used to generate distributions of the credible proportions of subjects likely to present with staining in a single peripheral zone, with or without central zone staining. It illustrated that staining in a peripheral zone without central staining was more credible. The worst single zone staining was most likely to present in the inferior zone (67.9%), followed by the nasal zone (11.3%), the superior zone (9.2%), and the temporal zone (5.6%).

Conclusion
In the presence of dry eye symptoms, the inferior zone typically presents the most severe grade of corneal staining, more likely without central zone staining. This knowledge is valuable when developing a strategy to treat dry eye signs, as the inferior corneal zone has the highest grade of staining thus has the potential to exhibit the greatest reduction in staining post-treatment.

2018

Blackie,C. A., Coleman,C. A., Nichols,K. K., Jones,L., Chen,P. Q., Melton,R., Kading,D. L., O’Dell,L. E., Srinivasan,S. A single vectored thermal pulsation treatment for meibomian gland dysfunction increases mean comfortable contact lens wearing time by approximately 4 hours per day Clinical Ophthalmology 2018;12:169-183 [ Show Abstract ]

Purpose: To evaluate the effect of a single vectored thermal pulsation (VTP) treatment in contact lens wearers with meibomian gland dysfunction (MGD) and dry eye symptoms. Methods: The prospective, nonsignificant risk, open-label, randomized, multi-center clinical trial included 55 soft contact lens (SCL) wearers with MGD and evaporative dry eye. Subjects were randomized to the single VTP treatment group or an untreated control. The controls received a crossover VTP treatment at 3 months (crossover treatment group). Primary effectiveness measures were meibomian gland secretion (MGS) score and Standard Patient Evaluation of Eye Dryness (SPEED) that were evaluated at baseline, at 1 and 3 months post-VTP treatment, and at 1 month post-VTP treatment in the crossover treatment group. Exploratory variables included fluorescein tear break-up time (TBUT), lid wiper epitheliopathy (LWE), lid parallel conjunctival folds (LIPCOF), ocular surface staining, frequency of over-the-counter (OTC) drop use, and hours of comfortable contact lens wear. Results: At 3 months, the treatment group showed significantly greater mean change from baseline in MGS (12.4±9.1 vs 1.4±6.4, p˂0.0001), SPEED (−8.4±4.7 vs −0.7±4.4, p˂0.0001) and significantly greater improvement in exploratory variables (TBUT, LWE, and frequency of OTC drop use) relative to the controls. Mean comfortable contact lens wearing time increased by 4.0±3.9 hours at 1 month. This was sustained for 3 months with no change in the control group. The crossover treatment group demonstrated similar results to the treatment group at 1 month post-VTP. Conclusion: In SCL wearers with MGD, a single VTP treatment significantly improved mean meibomian gland function and significantly reduced dry eye signs and symptoms compared to an untreated control. The treatment increased mean comfortable lens wearing time by 4 hours (approximately doubling the pretreatment findings). This was sustained for up to 3 months post-treatment on average.

Chen,P. Z., Pollit,L., Jones,L., Gu,F. X. Functional Two- and Three-Dimensional Architectures of Immobilized Metal Nanoparticles Chem 2018;4(10):2301-2328 [ Show Abstract ]

Recent methodological advances have led to unprecedented precision in the immobilization of metal nanoparticles. These methodologies come from a broad range of disciplines and organize nanoparticle building blocks into a diverse selection of distinct architectures—from small arrays to ordered superstructures. Because properties can be dictated by assembly, architectures can present enhanced properties of the constituent nanoparticles or generate emergent properties of the collective architecture that are unavailable to their constituent nanoparticles. Functional architectures use these properties to further tailor and optimize performance in myriad applications. This review discusses the methodological advances that enable the immobilization of metal nanoparticles in distinct two- and three-dimensional architectures. Discussion will include their distinctions, properties associated with the assemblies and their applications, and the key challenges and future directions in this growing field. The integration of nanomaterials has transformed key applications in a multitude of scientific fields, such as in energy, environmental technologies, water, medicine, and chemical processing. Metal nanoparticles, the predominant type of nanomaterial, are at the center of many of these applications. Conventionally, the physical properties of metal nanoparticles, such as size and shape, are engineered to alter properties and enhance performance. Recent work has developed a new approach: immobilizing metal nanoparticles in architectures. These structures generate enhanced or emergent properties, which can be used to further improve performance in applications, and promise the next generation of applications of metal nanoparticles in science and society. This review discusses the methods (from a wide range of disciplines) that immobilize nanoparticles in precise two- and three-dimensional architectures. Also discussed are the properties that arise from and the utility of the architectures. Metal nanoparticles present enhanced, or emergent, properties when immobilized in precisely configured two- and three-dimensional architectures. Recent methodological advances in a broad range of fields enable the construction of a diverse selection of such architectures. This review discusses these methodologies, their constructed products, and the properties exhibited by the architectures. It also discusses the distinctions, sometimes subtle, between methodologies that often dictate the types of architectures that they can construct and thus the resultant properties that can be presented.

Delaveris,A., Stahl,U., Madigan,M., Jalbert,I. Comparative performance of lissamine green stains Contact Lens and Anterior Eye 2018;41(1):23-27 [ Show Abstract ]

Purpose To investigate the performance of lissamine green strips from different manufacturers. Additionally, the repeatability, need for sequential dye instillation and impact of repeated lid evertion on lid wiper staining were assessed. Methods Study 1 was a prospective, randomised cross-over study where controlled volumes of lissamine green solution prepared from strips (Biotech, Lissaver, GreenGlo, OPGreen) were instilled (right eye: single; left eye: double instillation) on five different days, with OPGreen being tested twice. Lids were everted and digital photographs taken, which were later assessed by a masked observer. Study 2 was an investigator-masked, randomised, controlled study testing the impact of single versus repeated lid evertion. Lid wiper staining was graded (0 to 3 in 0.5 steps). Results Lid wiper staining differed significantly between lissamine green solutions, with GreenGlo showing the highest amount of staining, and Lissaver the least (all p > 0.009). There were no differences in lid wiper staining over two days, using the OPGreen solution (all p > 0.05). The number of drops instilled (single versus double) did not significantly affect lid wiper staining (all p > 0.05). Repeated lid evertion increased lid wiper staining (p = 0.007 when combined with double drop instillation). Light absorbance patterns and measured concentrations aligned with clinical findings. Conclusion There were significant differences in performance between lissamine green solutions. Lid wiper staining was impacted by repeated lid evertion but sequential instillation and use of the Korb grading scale provided little advantage over simpler methods Clinicians must consider this when investigating lid wipers, especially when interpreting a negative finding. © 2017 British Contact Lens Association

Luensmann,D., Schaeffer,J. L., Rumney,N. J., Stanberry,A., Walsh,K., Jones,L. Spectacle prescriptions review to determine prevalence of ametropia and coverage of frequent replacement soft toric contact lenses Contact Lens and Anterior Eye 2018;41(5):412-420 [ Show Abstract ]

Purpose: To determine the prevalence of ametropia and astigmatism in a clinic population and to estimate the coverage of frequent replacement soft toric lenses. Methods: A review of patient files was conducted at three clinical sites. Prescription data collected between January 2014 and March 2017 in a patient cohort 14 to 70 years of age inclusive were analyzed to determine prevalence of ametropia and astigmatism. The percent coverage of frequent replacement soft toric contact lenses has further been estimated using different ranges for sphere, cylinder and axis availability. Results: In total 101,973 patients were included in the analysis of which 69.5% were considered myopic, 26.9% hyperopic and 3.5% emmetropic as determined by the eye with the larger absolute value of the spherical equivalent refraction. Astigmatism in at least one eye was found in 87.2% of the population, with 37.0% of the patients exhibiting astigmatism of at least −1.00DC in at least one eye. With-the-rule astigmatism was most prevalent in the 14 to 20 year-olds (53.0%), while against-the-rule astigmatism was most prevalent in the 41 to 70 year-olds (50.7%). For astigmatic eyes with a cylinder of at least −0.75DC (n = 83,540; 41% of all eyes), the coverage with toric soft lenses varied greatly depending on parameter availability and ranged between 30.7% (sphere: Plano to −3.00D, cylinder: up to −1.75DC, axes: 90 ± 10° and 180 ± 10°) and 96.4% (sphere: + 6.00D to −10.00D, cylinders: up to −2.75DC, 18 axes). Conclusion: Currently available frequent replacement soft toric contact lenses provide coverage for up to 96.4% of potential patients.

McCanna,D. J., Oh,S., Seo,J., Coles-Brennan,C., Fadli,Z., Subbaraman,L. N., Jones,L. W. The effect of denatured lysozyme on human corneal epithelial cells Investigative Ophthalmology and Visual Science 2018;59(5):2006-2014 [ Show Abstract ]

PURPOSE. During contact lens wear, the amount of lysozyme deposited on contact lenses varies depending on the lens material. The binding of lysozyme to some contact lens materials may result in a conformational change that denatures the protein to an inactive form. This investigation evaluated the effect that denatured lysozyme has on human corneal epithelial cells (HCECs) by measuring cell viability and the release of inflammatory cytokines. METHODS. HCECs were exposed to lysozyme that was denatured to various activity levels. After 24-hour exposure to the lysozyme (1.9 mg/mL) in growth media, the cells were evaluated for cell viability using confocal microscopy. The metabolic activity of the cells was determined using an alamarBlue assay. Cell supernatants were analyzed for inflammatory cytokines. RESULTS. Using confocal microscopy, there was no detectable change in the viability of the HCECs after exposure to the denatured lysozyme. However, using alamarBlue, a decrease in the metabolic activity of the HCECs exposed to denatured lysozyme was detected. HCECs exposed to lysozyme that was 67%, 47%, and 22% active showed a reduction in metabolic activity when compared with native (100% active) lysozyme and the media controls (P < 0.05). Exposure to the denatured lysozyme also caused an increase in the release of inflammatory cytokines (P < 0.05) from the HCECs. CONCLUSIONS. The results of this study show that denatured lysozyme can have a detrimental effect on HCECs. Both a reduction in metabolic activity and an increase in the release of inflammatory cytokines occurred after HCEC exposure to denatured lysozyme. © 2018 The Authors.

Moezzi,A., Hutchings,N., Fonn,D., Simpson,T. L. Mixed Model Analysis of Between-Subject Variability in Overnight Corneal Swelling and Deswelling With Silicone Hydrogel Lenses Invest Ophthalmol Vis Sci 2018;59(6):2576-85 [ Show Abstract ]

PURPOSE: To model between subject variability of corneal swelling (CS) and deswelling after overnight wear of silicone hydrogel (SiHy) contact lenses.

METHODS: A total of 29 neophyte subjects wore 12 SiHy lenses with central transmissibility range of 31 to 211 Dk/t units on separate nights, in random order, and on one eye only. The contralateral eye served as the control. Central corneal thickness was measured using digital optical pachymetry before lens insertion, immediately after lens removal on waking, then 20, 40 minutes, 1, 2, and 3 hours later. Mixed modelling was conducted for simultaneous analysis of group and between-subject effects of CS and deswelling.

RESULTS: The best model for overnight CS versus Dk/t was linear with a random intercept showing constant between-subject differences in CS for different Dk/t values. The best fit for corneal deswelling versus time was a curvilinear random intercept and random slope model. About 90% of the total between-subject deswelling variance in either lens or control eyes was due to the intercept variability with much less (∼10%) being due to the variability of the individual deswelling rate (slope). Subject age, sex, and ametropia were not predictors of individual corneal swelling in the swelling versus Dk/t analysis. Age, however, was a significant (inverse) predictor of the rate of corneal deswelling, only in lens-wearing eyes.

CONCLUSIONS: A large proportion of variability in corneal swelling is because of subject-specific differences in corneal response to hypoxia. This shows that "low swellers" and "high swellers" actually do exist.

Ng,A. Y., Keech,A., Jones,L. Tear osmolarity changes after use of hydroxypropyl-guar-based lubricating eye drops Clinical Ophthalmology 2018;12:695-700 [ Show Abstract ]

Purpose: To evaluate tear osmolarity after using a hydroxypropyl-guar (HP-guar)-based lubricating eye drop four times daily (QID) for 3 weeks. Methods: Thirty-one participants with dry eye disease (Ocular Surface Disease Index [OSDI] score ≥20 and tear osmolarity ≥300 mOsm/L in at least one eye) were enrolled in this prospective, dispensing, non-randomized study involving a baseline visit and 3‑week follow-up. Tear osmolarity, non-invasive tear break up time (NITBUT), conjunctival hyperemia, corneal and conjunctival staining were determined at baseline. Participants were instructed to instill one drop of a HP-guar-based drop QID in each eye for 3 weeks. At the follow-up visit, the symptoms and ocular surface parameters were reassessed. At this visit, one HP-guar drop was instilled into each eye and osmolarity was measured after 15 minutes, to examine short-term changes in osmolarity. Results: Twenty-eight participants completed the study (5M, 23F; median age 54 yrs, range 25-83 yrs). At baseline, mean OSDI score was 44.9±15.2 and mean osmolarities were 314.63±11.9/306.6±10.1 mOsm/L (worst eye [WE]/better eye [BE]). After 3 weeks, mean osmolarity reduced to 307.7±15.7/303.9±11.3 mOsm/L (WE/BE; p<0.05 and p=0.228, respectively) and mean OSDI scores reduced to 28.3±17.0 (p<0.01). A significant reduction in osmolarity was observed 15 minutes after instilling the lubricating drop (p<0.05 WE, p=0.09 BE). Significant improvements in central corneal staining (p<0.05 OU) and NITBUT (p0.05). Conclusions: A significant reduction in tear osmolarity and improvements in dry eye symptoms, corneal staining, and NITBUT were observed after 3 weeks of QID use of a HP-guar-based lubricant drop. A decrease in osmolarity was also demonstrated 15 minutes after drop instillation.

Ngo,W., Jones, L., Bitton, E. Short-Term Comfort Responses Associated With the Use of Eyelid Cleansing Products to Manage Demodex folliculorum Eye and Contact Lens 2018;44(Suppl 2):S87-S92 [ Show Abstract ]

PURPOSE: To quantify the discomfort over time of various eyelid cleansers against Demodex.
METHODS: This was a prospective, randomized, controlled, crossover, open-label study that enrolled 26 participants. The cleansers used in this study were Biotissue Cliradex (CD), OCuSOFT Lid Scrubs Plus (OP), OCuSOFT OUST Demodex Swabstix (ODS), TheraTears Theralid (TT), NovaBay Avenova (NA). Bausch+Lomb Sensitive Eyes Plus saline was used as a control. Participants were asked to close their eyes as the product was gently rubbed (10 cycles of gentle lateral motion) into the eyelashes. Participants verbally rated their discomfort (0 = no discomfort, 10 = maximum tolerable discomfort) every 15 sec for the first 5 min, and every 30 sec for 5 min after, for a total of 10 min. The order of products used was randomized, and washout period between cleansing was 48 hr.
RESULTS: Twenty-five participants completed the study (mean age=26±6). There was no significant difference in discomfort scores at pre-application. The discomfort levels of saline, OP, and NA over the 10-min period were not significantly different than their pre-application discomfort at all time points (all P≥0.99). The discomfort of CD was significantly higher than pre-application levels between t=15 sec and t=180 sec (all P≤0.01), with maximum median (interquartile range [IQR]) discomfort of 3.0 (5.0) occurring at t=45 sec. The discomfort of TT was significantly higher than pre-application levels between t=45 and t=90 (all P<0.02), with maximum median (IQR) discomfort of 1.0 (1.5) occurring at t=75 sec. The discomfort of ODS was significantly higher than pre-application levels starting from t=60 sec and onward, with maximum median (IQR) discomfort of 6.0 (5.0) occurring at t=300 sec.
CONCLUSION: Of the cleansers used in this study, the ones that induced significant discomfort were CD, TT, and ODS. The results from this study may help clinicians educate patients about what to expect when approaching the topic of eyelid Demodex treatment.

Ngo,W., Srinivasan,S., Jones, L., A comparison of dry eye diagnostic tests between symptomatic and asymptomatic age-matched females Eye and Contact Lens 2018;44(Suppl 1):S110-S114 [ Show Abstract ]

PURPOSE: To quantify the strength of association of dry eye (DE) symptoms to DE diagnostic tests in age-matched females.
METHODS: Twenty females with DE symptoms (Ocular Surface Disease Index, OSDI, ≥13) were age-matched with 20 females without DE symptoms (OSDI<13) in this cross-sectional study. Noninvasive tear breakup time (NIBUT), ocular staining, meibum quality, number of obstructed meibomian glands (MGs), lid wiper epitheliopathy, Marx line placement, eyelid margin score, Schirmer test, meibography, and visual acuity were assessed in both groups.
RESULTS: Twenty participant pairs completed the study. The age (median/interquartile range [IQR]) of the symptomatic group was 60/15 and the asymptomatic group was 62/15. The tests (median/IQR, P value) that were significantly different between the symptomatic group and the asymptomatic group were OSDI (35.4/35.4 vs. 3.1/6.7, P<0.01), NIBUT (2.1/0.7 sec vs. 3.0/3.0 sec, P=0.01), meibum quality (3.0/0.0 grade units vs. 2.0/1.0 grade units, P<0.01), number of obstructed MGs (7.0/2.0 glands vs. 5.0/4.8 glands, P<0.01), and ocular staining (5.5/3.8 grade units vs. 0.5/1.0 grade units, P<0.01). The tests (area under curve, [AUC], odds ratio [OR]) that were most strongly associated with DE symptoms were ocular staining (0.93, 5.0), number of obstructed MGs (0.79, 2.6), meibum quality (0.76, 2.4), and NIBUT (0.74, 3.2) (all P0.05), and similarly, no significant association to DE symptoms (all P>0.05).
CONCLUSION: The diagnostic tests most strongly associated with DE symptoms in older women were ocular staining, meibum quality, number of obstructed MGs, and tear film stability.

Oh,S., McCanna,D., Subbaraman,L.N., Jones,L. Cytotoxic and inflammatory effects of contact lens solutions on human corneal epithelial cells in vitro Contact Lens and Anterior Eye 2018;41(3):282-289 [ Show Abstract ]

Purpose: To ascertain the effect that four contact lens (CL) multipurpose solutions (MPS) have on the viability and release of pro-inflammatory cytokines from human corneal epithelial cells (HCEC). Methods: HCEC were exposed to four different MPS at various concentrations for 18 hours. The cells were also exposed to phosphate buffer, borate buffer, and PHMB. The cell viability was evaluated using the alamarBlue assay. The release of pro-inflammatory cytokines was measured using a Multiplex electrochemiluminescent assay. Results: MPS-A, MPS-B and MPS-C all reduced cell metabolic activity p < 0.05 from control with MPS-A showing the greatest cytotoxic effect (maximum reduction, 90.6%). In contrast, MPS-D showed no significant reductions in cytotoxicity except at the highest concentration tested (19% reduction at 20% MPS concentration). Of the four cytokines evaluated MPS-C showed a substantial increase in the release of IL-1β, IL-6, IL-8, and TNF-α at higher concentrations when compared to control p < 0.05. At the 20% concentration of MPS-A and MPS-B the release of IL-1 β increased p 0.05. Exposing the cells to borate buffer and PHMB caused an increase in the release of TNF-α p < 0.05. Conclusions: This investigation demonstrates that at different concentration levels, several of the MPS tested showed a decrease in viability and an increase in the release of inflammatory cytokines from HCEC. The borate buffer component as well as PHMB appears to contribute to this pro-inflammatory reaction.

Omali,N.B., Subbaraman,L.N., Heynen,M., Ng,A., Coles-Brennan,C., Fadli,Z., Jones,L. Surface versus bulk activity of lysozyme deposited on hydrogel contact lens materials in vitro Contact Lens and Anterior Eye 2018;41(4):329-334 [ Show Abstract ]

Purpose: To determine and compare the levels of surface versus bulk active lysozyme deposited on several commercially available hydrogel contact lens materials. Methods: Hydrogel contact lens materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon and etafilcon A with polyvinylpyrrolidone (PVP)] were incubated in an artificial tear solution for 16 h. Total activity was determined using a standard turbidity assay. The surface activity of the deposited lysozyme was determined using a modified turbidity assay. The amount of active lysozyme present within the bulk of the lens material was calculated by determining the difference between the total and surface active lysozyme. Results: The etafilcon A materials showed the highest amount of total lysozyme activity (519 ± 8 μg/lens, average of Moist and Define), followed by the ocufilcon material (200 ± 5 μg/lens) and these two were significantly different from each other (p < 0.05). The amount of surface active lysozyme on etafilcon and ocufilcon lens materials was significantly higher than that found on all other lenses (p < 0.05). There was no active lysozyme quantified in the bulk of the nelfilcon material, as all of the active lysozyme was found on the surface (1.7 ± 0.3 μg/lens). In contrast, no active lysozyme was quantified on the surface of polymacon, with all of the active lysozyme found in the bulk of the lens material (0.6 ± 0.6 μg/lens). Conclusions: The surface and bulk activity of lysozyme deposited on contact lenses is material dependent. Lysozyme deposited on ionic, high water content lens materials such as etafilcon A show significantly higher surface and bulk activity than many other hydrogel lens materials.

Otchere,H., Jones,L., Sorbara,L. The Impact of Scleral Contact Lens Vault on Visual Acuity and Comfort. Eye and Contact Lens 2018;44(Suppl 2):S54-S59 [ Show Abstract ]

PURPOSE: To assess how varying degrees of corneal clearance of scleral contact lenses (ScCL) impact visual acuity (VA) and comfort in patients with corneal ectasia.
METHOD: Three ScCL were fitted to 20 subjects with previous diagnosis of either keratoconus (n=18) or pellucid marginal degeneration (n=2). Fitting of ScCL was based on corneal sagittal height (CSH) measured with Visante OCT at a 15-mm chord on the horizontal meridian. To select the ScCL from the diagnostic lens set, values of 325, 375, and 425 μm were randomly added in sequence to CSH. Subjects wore ScCL for 1 hr. Central corneal clearance (CCC) and topographic corneal clearance (TCC) along the vertical meridian were assessed using an ultralong optical coherence tomographer. High-contrast VA (HCVA) and low-contrast VA (LCVA) were measured using a logarithm of the minimum angle of resolution VA chart, and comfort ratings were obtained with a standard comfort scale (0-100).
RESULTS: Mean CSH in the horizontal meridian was 3.78±0.53 (range: 3.33-4.17) mm at a 15-mm chord. Mean CCC was 190±100 μm (TCC: 160±94 μm at +3 mm and 180±94 μm at -3 mm), 360±120 μm (TCC: 260±100 μm at +3 mm and 330±110 μm at -3 mm), and 450±170 μm (TCC: 320±120 μm at +3 mm and 400±120 μm at -3 mm) for each lens (P=0.001). Mean HCVA for lenses 1, 2, and 3 were 0.05±0.12, 0.07±0.11, and 0.11±0.08 respectively, which were significantly different (P=0.02). Tukey post hoc analysis showed that this difference was only significant between lenses 1 and 3 (P=0.01). Similar findings were found for LCVA. Comfort ratings for lenses 1, 2, and 3 were 74.9±9.2, 79.7±11.6, and 78.6±10.8, respectively (P=0.24).
CONCLUSION: The CSH is an effective method of determining the appropriate lens/cornea relationship. Lens 2 (+375 μm) gave the best combination of acuity and comfort ratings. Evaluation of the fluorescein pattern must be balanced with VA and comfort ratings for successful fitting in a clinical setting.

Phan,C. -M, Walther,H., Smith,R. W., Riederer,D., Lau,C., Lorenz,K. O., Subbaraman,L. N., Jones L. Determination of the release of PEG and HPMC from nelfilcon A daily disposable contact lenses using a novel in vitro eye model. J Biomater Sci Polym Ed 2018;29(17):2124-2136 [ Show Abstract ]

The traditional method to measure release of components from CLs is a vial containing a static volume of PBS (phosphate buffered saline). However, this model does not simulate physiologically relevant tear volume and natural tear flow, air exposure, and mechanical rubbing. These factors can significantly impact release kinetics. We have developed an in vitro eye model (OcuFlow) that simulates these parameters. The aim of the study was to measure the release of PEG (polyethylene glycol), and HPMC (hydroxypropyl methylcellulose) from a daily disposable hydrogel contact lens material (nelfilcon A; Dailies AquaComfort PLUS; DACP;) over 24 hrs using the OcuFlow platform. The elution of PEG and HPMC from DACP lenses was analyzed using LCMS (liquid chromatography mass spectrometry). The release of all wetting agents from the lenses followed a burst release pattern, which occurred within the first 1.5 hrs (P < 0.05). The release of PEG was greater than that of HPMC (P < 0.05). The amount of PEG and HPMC released at any given time was less than 1% of the amount in the blister pack solution. Our results suggest that HPMC and PEG are rapidly released from the CL.

Phan,C. -M, Weber,S., Mueller,J., Yee,A., Jones,L. A rapid extraction method to quantify drug uptake in contact lenses Translational Vision Science and Technology 2018;7(2):11 [ Show Abstract ]

Purpose: To develop a simple extraction procedure to quantify the uptake of four topical ocular pharmaceutical drugs into contact lenses (CLs). Methods: Four silicone hydrogel (SH) CLs (balafilcon A, senofilcon A, lotrafilcon B, comfilcon B) and four conventional hydrogel (CH) CLs (nesofilcon A, hilafilcon B, nelfilcon A, etafilcon A) were evaluated. The drugs studied were natamycin, moxifloxacin, timolol maleate, and ketotifen fumarate. For drug incubation, three CLs of each type were placed in 1 mL of 1 mg/mL drug-loading solution for 24 hours. The lenses were then extracted in 2 mL methanol for 2 hours. This process was repeated to obtain a total of three extraction cycles. Detection of natamycin, moxifloxacin, ketotifen fumarate, and timolol maleate were measured by absorbance at 305, 287, 297, and 295 nm, respectively. Results: The majority of the drugs were extracted after the first extraction cycle (P 0.05). Conclusions: This study provides a simple approach to determine drug uptake into CLs. This method can also be modified, such as changing the extraction time, extraction cycles, or extraction solvent to better suit other drugs and CL combinations. Translational Relevance: There is considerable interest in using CLs for ocular drug delivery. Accurately quantifying drug uptake on CLs has been a challenge. Hence, this study provides a simple method to quantify drug uptake in CLs. © 2018 The Authors.

Qiao,H., Phan,C. -M., Walther,H., Subbaraman,L. N., Jones,L. Depth Profile Assessment of the Early Phase Deposition of Lysozyme on Soft Contact Lens Materials Using a Novel In Vitro Eye Model 2018;44(Suppl 2):S11-S18 [ Show Abstract ]

OBJECTIVE: To characterize the location of fluorescently labeled lysozyme on commercial contact lenses (CLs) using an in vitro eye model that simulates tear volume, tear flow, air exposure, and mechanical wear.
METHODS: One commercially available conventional hydrogel CL material (etafilcon A) and three silicone hydrogel CL materials (balafilcon A, lotrafilcon B, and senofilcon A) were evaluated in this study. The CLs were mounted on the in vitro eye model and exposed to artificial tear fluid containing fluorescein isothiocyanate (FITC)-labeled lysozyme for 2 and 10 hrs. After these short incubation periods, circular discs were punched from the CLs at the center and periphery and were prepared for confocal laser scanning microscopy (CLSM). The CLSM captured a series of consecutive images spaced 5 μm apart, and the resulting images were rendered into two dimensional cross-sectional views of the CL. The mean fluorescence at each 5 μm slice was used to generate a histogram depicting the penetration of FITC-lysozyme into CLs.
RESULTS: For both incubation periods, the CLSM images and histogram of etafilcon A showed that FITC-lysozyme is more concentrated at the lens surface, with a moderate amount of deposition in the lens matrix. For balafilcon A, FITC-lysozyme was evenly distributed throughout the lens. For lotrafilcon B, there was a greater amount of FITC-lysozyme deposition on the surfaces of the lens versus the matrix. Senofilcon A had differential FITC-lysozyme distribution profiles depending on the location of the lens. At the lens periphery, FITC-lysozyme primarily deposited on the surface, whereas FITC-lysozyme was uniformly distributed at the center of the lens.
CONCLUSIONS: With the use of a sophisticated in vitro eye model, the study revealed a complex deposition pattern of FITC-labeled lysozyme on various CL materials after short periods of exposure. An understanding of the early deposition pattern of lysozyme on different CL material may elucidate new insights into the processes behind CL discomfort.

Stahl,U., Jalbert,I. Exploring the links between contact lens comfort, osmolarity and lid wiper staining Contact Lens and Anterior Eye 2018;41(1):110-116 [ Show Abstract ]

Purpose Contact lens discomfort remains poorly understood, not least due to lack of associations between clinical signs and symptoms. This study aimed to explore the relationships between osmolarity, comfort and lid wiper epitheliopathy in contact lens wear. Methods Twenty subjects participated in a randomized, cross-over study where comfilcon A and lotrafilcon A lenses were each worn for 10 days separated by a 7 days washout period. Tear and contact lens osmolarity, ocular symptoms including comfort, tear stability and production, and lid wiper epitheliopathy were measured. Results Comfort and tear stability decreased and upper lid wiper staining and foreign body sensation increased with lens wear. These were not affected by lens type. A reduction in tear production was seen after 10 days of comfilcon A lens wear. High proportions of lid wiper epitheliopathy were observed at the upper (range 65%–85%) and lower (range 90%–100%) lid margins. Tear and contact lens osmolarity were unaffected by lens wear or type. Contact lens osmolarity was associated with comfort (r = 0.45, p = 0.009). Tear osmolarity moderately correlated with tear stability (r = -0.53, p = 0.014) and tear production (r = -0.44, p = 0.012) but not with lid wiper staining. Conclusions A relationship between comfort and contact lens osmolarity and between tear osmolarity and tear stability and production were found, however, this study was unable to demonstrate an association between comfort and tear osmolarity or lid wiper epitheliopathy. Further studies using contact lenses with a wider range of comfort responses are warranted to investigate these associations further. © 2017 British Contact Lens Association

Wallerstein,A., Jackson,W.B., Chambers,J., Moezzi,A., Lin,H., Simmons,P.A Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose Clinical Ophthalmology 2018;12:839-848 [ Show Abstract ]

Purpose: To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK).
Methods: This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer’s test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled.
Results: A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer’s test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated.
Conclusion: CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK.

Walther,H., Phan,C. -M., Subbaraman,L. N., Jones,L. Differential deposition of fluorescently tagged cholesterol on commercial contact lenses using a novel in vitro eye model Translational Vision Science and Technology 2018;7(2):18 [ Show Abstract ]

Purpose: We evaluate the differences in lipid uptake and penetration in daily disposable (DD) contact lenses (CL) using a conventional “in-vial” method compared to a novel in vitro eye model. Methods: The penetration of fluorescently labelled 22-(N-(7-Nitrobenz-2-Oxa-1,3- Diazol-4-yl)Amino)-23,24-Bisnor-5-Cholen-3beta-Ol (NBD)–cholesterol on three silicone hydrogel (SH) and four conventional hydrogel (CH) DD CLs were investigated. CLs were incubated for 4 and 12 hours in a vial, containing 3.5 mL artificial tear solution (ATS), or were mounted on an in vitro eye-blink platform designed to simulate physiologic tear flow (2 mL/24 hours), tear volume and “simulated” blinking. Subsequently, CLs were analyzed using laser scanning confocal microscopy and ImageJ. Results: Penetration depth and fluorescence intensities of NBD-cholesterol varied between the incubation methods as well as lens materials. Using the traditional vial incubation method, NBD-cholesterol uptake occurred equally on both sides of all lens materials. However, using our eye-blink model, cholesterol penetration was observed primarily on the anterior surface of the CLs. In general, SH lenses showed higher intensities of NBD-cholesterol than CH materials. Conclusions: The traditional “in-vial” incubation method exposes the CLs to an excessively high amount of ATS, which results in an overestimation for cholesterol deposition. Our model, which incorporates important ocular factors, such as intermittent air exposure, small tear volume, and physiological tear flow between blinks, provides a more natural environment for in vitro lens incubation. Translational Relevance: In vitro measurements of CLs are a common approach to predict their interactions and performance on the eye. Traditional methods, however, are rudimentary. Therefore, this study presents a novel in vitro model to evaluate CLs, which consequently will enhance elucidations of the interactions between CLs and the eye.

Wong,S., Murphy,P.J., Jones,L. Tear evaporation rates: What does the literature tell us? Contact Lens and Anterior Eye 2018;41(3):297-306 [ Show Abstract ]

Purpose: A previous literature review reported tear evaporation rates (TERs) from studies conducted on rabbits and humans between 1941 and 2003. Closer examination of the presented data revealed inaccuracies in the reporting of some values. This paper presents updated tables of TERs using values from the original papers cited in the review, in addition to incorporating new studies published between 2003 and 2016. Methods: A copy of each paper cited in the literature review was obtained and checked against the evaporation rate reported in the review. If the expected value could not be found in the cited paper, other papers by the same author were consulted to see if the value had been reported elsewhere. A PubMed and Scopus database search was conducted to find papers published on tear evaporimetry since 2003. Results: Two new tables of TERs were created, based on the values reported by the original author. To aid in interpretation, the majority of results are expressed in units of x 10−7 g/cm2/sec. Where it was not possible to convert these values, some values are expressed as x 10−7 g/sec, x 10−7 g/sec/eye or W/min. Conclusions: Two new tables of TERs have been compiled to provide an accurate representation of the values reported in the original papers. These tables can be used as a point of reference for other researchers to compare their results.

Woods,J., Varikooty,J., Fonn,D., Jones,L. A novel scale for describing corneal staining Clinical Ophthalmology 2018;12:2369-2375 [ Show Abstract ]

The assessment of corneal staining is a commonly conducted procedure in both clinical practice and as part of various research studies. Different grading scales are employed by many clinicians and researchers to undertake this procedure for corneal staining comparisons between eyes, products and over time. This paper describes the development and use of a grading scale for corneal staining undertaken at an academic research site. The scale involves assessment of three factors across five corneal zones: type, area and depth. Staining type and area are graded on a 0–100 scale, and depth is graded on a 0–4 scale. These factors can be combined to create a three- or two-factor staining grade, or the factors may be reported individually. An additional benefit of this scale is that the staining scores may be reported by zone as “zone staining scores” or the scores of zones may be combined to provide an overall corneal “global staining score”.

Yang,M., Luensmann,D., Fonn,D., Woods,J., Jones,D., Gordon,K., Jones,L. Myopia prevalence in Canadian school children: A pilot study Eye 2018;32(6):1042-1047 [ Show Abstract ]

Purpose: A pilot study to determine the prevalence of myopia, proportion of uncorrected myopia and pertinent environmental factors among children in a suburban region in Canada. Methods: Refraction with cycloplegia and ocular biometry were measured in children of two age groups. Myopia was considered at a spherical equivalent refraction (SER) ≤-0.50 D in at least one eye. Parents completed a questionnaire that captured the child's daily activities. Results: A total of 166 children completed the study (83 aged 6-8 and 83 aged 11-13). Myopia prevalence was 17.5% among the overall group, 6.0% among ages 6-8 and 28.9% among ages 11-13. Mean subjective SER in myopic children was -1.10 D (95% confidence interval (CI), -0.34 to -1.86 D) at ages 6-8 and -2.44 D (95% CI, -1.71 to -3.18 D) at ages 11-13. In this study, 34.5% of the myopic children were uncorrected, which represented 6.0% of the entire group of children. Mean axial length (AL) increased by 1.03 mm from ages 6-8 (mean 22.62 mm; 95% CI, 22.45 to 22.79 mm) to ages 11-13 (mean 23.65 mm; 95% CI, 23.45 to 23.84 mm; p < 0.01). The correlation coefficient between AL and SER was -0.618 (p < 0.01). Binary logistic regression between outdoor time and the prevalence of myopia showed that one additional hour of outdoor time per week lowered the odds of a child having myopia by 14.3% (p = 0.007). Conclusion: Myopia prevalence increased from 6% at ages 6-8 to 29% at ages 11-13. Thirty-five per cent of the myopes in this study were uncorrected. More time outdoors may be beneficial to protect against myopia onset.

2017

Craig,J. P., Nelson,J. D., Azar,D. T., Belmonte,C., Bron,A. J., Chauhan,S. K., de Paiva,C. S., Gomes,J. A. P., Hammitt,K. M., Jones,L., Nichols,J. J., Nichols,K. K., Novack,G. D., Stapleton,F. J., Willcox,M. D. P., Wolffsohn,J. S., Sullivan,D. A. TFOS DEWS II Report Executive Summary Ocular Surface 2017;15(4):802-812 [ Show Abstract ]

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.

Craig,J. P., Nelson,J. D., Azar,D. T., Belmonte,C., Bron,A. J., Chauhan,S. K., de Paiva,C. S., Gomes,J. A. P., Hammitt,K. M., Jones,L., Nichols,J. J., Nichols,K. K., Novack,G. D., Stapleton,F. J., Willcox,M. D. P., Wolffsohn,J. S., Sullivan,D. A. TFOS DEWS II Report Executive Summary Ocular Surface 2017;15(4):802-812 [ Show Abstract ]

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.

Hall,B., Forrest,J. A., Jones,L. A Review of Techniques to Measure Protein Sorption to Soft Contact Lenses Eye and Contact Lens 2017;43(5):276-286 [ Show Abstract ]

Purpose: To compare and critically evaluate a variety of techniques to measure the quantity and biological activity of protein sorption to contact lenses over short time periods. Methods: A literature review was undertaken investigating the major techniques to measure protein sorption to soft contact lens materials, with specific reference to measuring protein directly on lenses using in situ, ex situ, protein structural, and biological activity techniques. Results: The use of in situ techniques to measure protein quantity provides excellent sensitivity, but many are not directly applicable to contact lenses. Many ex situ techniques struggle to measure all sorbed proteins, and these measurements can have significant signal interference from the lens materials themselves. Techniques measuring the secondary and tertiary structures of sorbed proteins have exhibited only limited success. Conclusions: There are a wide variety of techniques to measure both the amount of protein and the biological activity of protein sorbed to soft contact lens materials. To measure the mass of protein sorbed to soft contact lenses (not just thin films) over short time periods, the method of choice should be I 125 radiolabeling. This technique is sensitive enough to measure small amounts of deposited protein, provided steps are taken to limit and measure any interaction of the iodine tracer with the materials. To measure the protein activity over short time periods, the method of choice should be to measure the biological function of sorbed proteins. This may require new methods or adaptations of existing ones. © 2017 Contact Lens Association of Ophthalmologists.

Heynen,M., Babaei Omali,N., Fadli,Z., Coles-Brennan,C., Subbaraman,L. N., Jones,L. Selectivity and localization of lysozyme uptake in contemporary hydrogel contact lens materials Journal of Biomaterials Science, Polymer Edition 2017;28(13):1351-1364 [ Show Abstract ]

The purpose of this study was to investigate the early and selective uptake of lysozyme and the location of deposited lysozyme on contemporary hydrogel contact lens (CL) materials after exposure to an artificial tear solution (ATS) for 16 h. Seven different hydrogel CL materials [polymacon, omafilcon A, nelfilcon A, nesofilcon A, ocufilcon B, etafilcon A (Acuvue Moist), and etafilcon A (Acuvue Define)] were incubated in an ATS for various times. Total protein deposition was determined using a modified Bradford technique. Lysozyme, lactoferrin, and albumin deposition on CLs were determined using 125I-radiolabeling method. A confocal laser scanning microscopy (CLSM) technique was utilized to map the location of lysozyme uptake in an asymmetric environment. All lens materials had significant amounts of lysozyme after 1 min of exposure to ATS. After 16 h of incubation, higher levels of total protein deposited on the two etafilcon A-based lenses (Moist and Define), followed by ocufilcon B and both were significantly higher than all other CLs tested (p = 0.0001). The two etafilcon A materials (Moist and Define) also deposited the highest amounts of lysozyme (514.8 ± 28.4 and 527.1 ± 14.7 µg/lens respectively) when compared to other test CLs (p = 0.0001). The CLSM technique revealed that the non-ionic CLs tended to have symmetric distribution of lysozyme throughout the lens materials, while the ionic CLs had an asymmetric distribution, with the highest concentration of lysozyme on and near the exposed surface. The quantity and nature of proteins deposited on CLs varies, depending upon the chemical composition of the material. Among the various lenses tested, etafilcon A deposited the highest amount of total protein, most of it represented by lysozyme, which was largely located near the surface of the lens. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Hui,A., Bajgrowicz-Cieslak,M., Phan,C. -M, Jones,L. In vitro release of two anti-muscarinic drugs from soft contact lenses Clinical Ophthalmology 2017;11:1657-1665 [ Show Abstract ]

The purpose of this study was to investigate the release of the anti-myopia drugs atropine sulfate and pirenzepine dihydrochloride from commercially available soft contact lenses. Standard ultraviolet (UV) absorbance-concentration curves were generated for atropine and pirenzepine. Ten commercially available contact lenses, including four multifocal lenses, were loaded by soaking in atropine or pirenzepine solutions at two different concentrations (10 mg/mL and 1 mg/mL). The release of the drugs into phosphate-buffered saline was determined over the course of 24hours at 34°C using UV absorbance. Materials with surface charge released the greatest amount of atropine when loaded with either concentration when compared to the other lens types (p<0.05), releasing upward of 1.026±0.035mg/lens and 0.979±0.024mg/lens from etafilcon A and ocufilcon A, respectively. There were no significant differences in the amount of atropine or pirenzepine released from the multifocal and non-multifocal lenses made from the same lens materials. Narafilcon A material demonstrated prolonged release of up to 8 hours when loaded with pirenzepine, although the overall dose delivered from the lens into the solution was among the lowest of the materials investigated. The rest of the lenses reached a plateau within 2 hours of release, suggesting that they were unable to sustain drug release into the solution for long periods of time. Given that no single method of myopia control has yet shown itself to be completely effective in preventing myopia progression, a combination of optical and pharmaceutical devices comprising a drug delivering contact lens presents a novel solution that warrants further investigation. © 2017 Hui et al.

Jones,L., Downie,L. E., Korb,D., Benitez-del-Castillo,J. M., Dana,R., Deng,S. X., Dong,P. N., Geerling,G., Hida,R. Y., Liu,Y., Seo,K. Y., Tauber,J., Wakamatsu,T. H., Xu,J., Wolffsohn,J. S., Craig,J. P. TFOS DEWS II Management and Therapy Report Ocular Surface 2017;15(3):575-628 [ Show Abstract ]

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

Nelson,J. D., Craig,J. P., Akpek,E. K., Azar,D. T., Belmonte,C., Bron,A. J., Clayton,J. A., Dogru,M., Dua,H. S., Foulks,G. N., Gomes,J. A. P., Hammitt,K. M., Holopainen,J., Jones,L., Joo,C. -K, Liu,Z., Nichols,J. J., Nichols,K. K., Novack,G. D., Sangwan,V., Stapleton,F., Tomlinson,A., Tsubota,K., Willcox,M. D. P., Wolffsohn,J. S., Sullivan,D. A. TFOS DEWS II Introduction Ocular Surface 2017;15(3):269-275

Ngo,W., Srinivasan,S., Houtman,D., Jones,L. The relief of dry eye signs and symptoms using a combination of lubricants, lid hygiene and ocular nutraceuticals Journal of Optometry 2017;10(1):26-33 [ Show Abstract ]

Purpose To determine the combined effect of TheraTears® Lubricant Eye Drops, TheraTears® SteriLid Eyelid Cleanser, and TheraTears® Nutrition on dry eye signs and symptoms. Methods This prospective study enrolled 28 dry eye participants. Participants were instructed to use the Lubricant Eye Drops at least 2–4× a day, SteriLid 1–2× a day, and Nutrition 3 gel caps once a day. Participants were followed up at baseline, 1 month and 3 months. Outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) questionnaire, non-invasive tear break-up time (NIBUT), osmolarity, number of meibomian glands blocked (#MG blocked), meibum quality, eyelid margin features, Schirmer's test, tear film lipid layer thickness (LLT), meniscus height, corneal and conjunctival staining. Results Twenty participants (mean age = 43, from 23 to 66, 17F, 3M) completed the study. Participants reported having used, on average, the Lubricant Eye Drop 2.4×/day, the SteriLid 1.1×/day, and the Nutrition 3 gel caps 1×/day. There was a significant change over time (p < 0.05) for OSDI (-21.2 points), SANDE (-32.4 points), NIBUT (+0.43 s), eyelid margin features (-1.1 grade), meibum quality (-1.0 grade), and #MG blocked (-4.0 glands). Conclusion By using a combination of TheraTears® Lubricant Eye Drop, SteriLid, and Nutrition, patients experience significant relief in both dry eye symptoms and signs. © 2016 Spanish General Council of Optometry

Ngo,W., Srinivasan,S., Keech,A., Keir,N., Jones,L. Self versus examiner administration of the Ocular Surface Disease Index© Journal of Optometry 2017;10(1):34-42 [ Show Abstract ]

Purpose To compare the difference in Ocular Surface Disease Index© (OSDI) scores when participants were given the OSDI to complete on their own (self-guided, SG), versus under the guidance of the examiner (examiner-guided, EG). Methods 100 participants enrolled in this prospective two-visit study (fifty under-45 years old, 38F/12M; and fifty 45 years-and-older, 42F/8M). Participants who scored =1 on the Subjective Evaluation of Symptoms of Dryness (SESoD) were included in this study. Participants completed the OSDI SG during the first visit. Participants returned the next day and repeated the OSDI, but with EG (with standardized instructions). Participants were under deception and believed that they were comparing the OSDI to the SESoD. Results The mean OSDI score of the SG and EG administration was 32.0 ± 17.3 and 33.8 ± 19.6 respectively (p > 0.05) with 95% limits of agreement between -20.6 and +24.2. The correlation between SG and EG administration was Spearman's r = 0.81, p 0.05) for both the under-45 group, and 45-and-older group. The 95% limits of agreement for the under-45 group were smaller than the 45-and-older group (under-45: [-15.5, +13.1,], 45-and-older: [-23.3, +32.2]). A significant difference was found between 8 of the 12 questions items (all p = 0.01). However, the mean difference for each was <0.6 and was not considered to be clinically significant. Conclusion There was no clinically significant difference in OSDI score between SG and EG administration, however having instructions provided with EG administration affected variability of scores in the older group more than the younger group. © 2016 Spanish General Council of Optometry

Omali,N. B., Lada,M., Lakkis,C., Morgan,P. B., Nichols,J. J., Subbaraman,L. N., Jones,L. W. Lipid Deposition on Contact Lenses when Using Contemporary Care Solutions Optometry and Vision Science 2017;94(9):919-927 [ Show Abstract ]

SIGNIFICANCE There remains only a small amount of data from human studies demonstrating the effect of contact lens/lens care solution combinations on the deposition of lipids. Therefore, information on the degree to which modern materials deposit lipids when used with contemporary care solutions would be valuable. PURPOSE The present study aims to determine the effect of lens care system combinations on levels of total lipid, cholesterol, and cholesteryl esters extracted from three different contact lenses (CLs) when used with four contemporary care systems. METHODS Experienced CL wearers were recruited to participate in this study. Combinations of three CLs (etafilcon A [ETA], galyfilcon A [GALY], and senofilcon A [SENO]) and four CL care solutions (Biotrue, ClearCare, OPTI-FREE PureMoist, and RevitaLens Ocutec) were investigated. A total of 791 CLs were analyzed. Subjects were randomized to one lens type and then used all four lens care solutions in random sequence for 10-14 days before the CLs were collected and analyzed for the amount of cholesterol, cholesteryl esters, and total lipids. RESULTS The mean range of cholesterol recovered across the different care solutions was 0.34-2.77 µg/lens, 3.48-4.29 µg/lens, and 4.75-6.20 µg/lens for ETA, SENO, and GALY lenses, respectively. Use of OPTI-FREE PureMoist with ETA lenses led to a significantly greater amount of cholesterol being recovered when compared to the use of the other solutions with ETA lenses (P .05). CONCLUSIONS This study did not demonstrate conclusively that any of the solution/CL combinations were superior to any of the other combinations when the amounts of lipid deposition were compared among the tested lenses. © Lippincott Williams & Wilkins.

Omali,N. B., Subbaraman,L. N., Heynen,M., Fadli,Z., Coles-Brennan,C., Jones,L. W. In Vitro Effect of Lysozyme on Albumin Deposition to Hydrogel Contact Lens Materials Optometry and Vision Science 2017;94(11):1047-1051 [ Show Abstract ]

SIGNIFICANCE: Albumin deposition on contact lenses could be detrimental to contact lens (CL) wear because this may increase the risk of bacterial binding and reduce comfort. Lysozyme deposition on selected lens materials would reduce albumin deposition on lenses. PURPOSE: This study aims to determine if lysozyme deposition on CLs could act as a barrier against subsequent albumin adsorption, using an in vitro model. METHODS: Six hydrogel CL materials (etafilcon A, polymacon, nelfilcon A, omafilcon A, ocufilcon B, and nesofilcon A) were evaluated. Four CLs of each type were soaked in lysozyme solution for 16 hours at 37°C. Lysozyme-coated lenses were then placed in vials with 1.5 mL of artificial tear solution containing 125I-labeled albumin for 16 hours at 37°C with shaking. Four uncoated lenses of each type were used as controls. Lenses soaked in radiolabeled albumin were rinsed in a phosphate-buffered saline solution, and radioactive counts were measured directly on lenses using a gamma counter. Albumin uptake on lenses was measured using a calibration curve by plotting radioactive counts versus protein concentration. RESULTS: Results are reported as mean ± SD. Lysozyme-coated etafilcon A lenses exhibited lower levels of deposited albumin than uncoated etafilcon A lenses (58 ± 12 vs. 84 ± 5 ng/lens; P .05). Uncoated nesofilcon A lenses deposited the highest amount of albumin when compared with other uncoated lenses (P <.05). CONCLUSIONS: This study demonstrates that lysozyme deposited onto etafilcon A resists the deposition of albumin, which may potentially be beneficial to CL wearers. Copyright © 2017 American Academy of Optometry.

Otchere,H., Jones,L. W., Sorbara,L. Effect of Time on Scleral Lens Settling and Change in Corneal Clearance Optometry and Vision Science 2017;94(9):908-913 [ Show Abstract ]

SIGNIFICANCE With the increase in the use of scleral contact lenses among practitioners, questions regarding lens settling are gradually gaining attention. This is because current studies support the notion that scleral lenses settle back over time. More research is needed to understand the exact cause and the factors that underpin such phenomenon. PURPOSE The present study aims to assess the effect of time on topographic corneal clearance of three scleral contact lenses of varying sagittal depths. METHODS Three scleral contact lenses were fitted to 20 subjects with previous diagnosis of keratoconus (n = 18) or pellucid marginal degeneration (n = 2). The fit was based on corneal sagittal height measured with the Visante optical coherence tomographer (OCT) at 15 mm along the horizontal meridian. To select an appropriate lens from the diagnostic lens set, values of 325 μm (lens 1), 375 μm (lens 2), and 425 μm (lens 3) were randomly added in sequence to the corneal sagittal height. Subjects wore each lens for 1 hour. Corneal clearance was measured at 10-minute intervals for 1 hour using a custom ultra-long OCT. To assess change in clearance, central point and two mid-peripheral points (+3 mm and -3 mm) along an 8-mm chord were measured by taking differences at each time point up to 1 hour. Measurements were repeated for the two other lenses. RESULTS Mean central corneal clearance loss for all three lenses was 33.83 ± 48.40 μm. This was 26 ± 27 μm (13 ± 14 μm, +3 mm; 34 ± 37 μm, -3 mm), lens 1; 35 ± 59 μm (38 ± 61 μm, +3 mm; 52 ± 69 μm, -3 mm), lens 2; and 41 ± 54 μm (33 ± 26 μm, +3 mm; 52 ± 48 μm, -3 mm), lens 3, respectively. There was no significant difference (P = 0.06) at central and other locations for lens 1 (location and over time). There were significant differences for both lenses 2 and 3 (P <.001, P =.01, respectively) for all three locations and over time. CONCLUSIONS There is a likelihood of clearance loss after 1 hour of lens wear. This varies between subjects, initial lens-fit relationship, and over time.

Regmi,S. C., Samsom,M. L., Heynen,M. L., Jay,G. D., Sullivan,B. D., Srinivasan,S., Caffery,B., Jones,L., Schmidt,T. A. Degradation of proteoglycan 4/lubricin by cathepsin S: Potential mechanism for diminished ocular surface lubrication in Sjögren's syndrome Experimental eye research 2017;161:1-9 [ Show Abstract ]

Sjögren's syndrome (SS) is an autoimmune disease affecting the lacrimal and salivary glands with hallmark clinical symptoms of dry eye and dry mouth. Recently, markedly increased cathepsin S (CTSS) activity has been observed in the tears of SS patients. Proteoglycan 4 (PRG4), also known as lubricin, is an effective boundary lubricant that is naturally present on the ocular surface. While PRG4 is susceptible to proteolytic digestion, the potential effect of CTSS on PRG4 remains unknown. The objective of this study was to assess the ability of CTSS to enzymatically degrade purified PRG4, and PRG4 naturally present in human tears, and alter ocular surface boundary lubricating properties. To assess the potential time course and dose-dependency of PRG4 digestion by CTSS, full-length recombinant human PRG4 (rhPRG4) was incubated at 37 °C with or without CTSS in an enzymatic digestion buffer. Digestion of PRG4 by CTSS was also examined within normal human tear samples, both with and without supplementation by rhPRG4. Finally, digestion of endogenous PRG4 by CTSS, and the effect of a CTSS inhibitor, was examined in SS tears on Schirmer strips. Digestion products were separated on 3–8% SDS-PAGE and visualized by protein staining and western blotting. The boundary lubricating ability of rhPRG4 samples was assessed using an in vitro human eyelid-cornea friction test. Finally, SDS-PAGE protein stain bands resulting from rhPRG4 digestion were submitted for tandem mass spectrometry analysis to confirm their identity as PRG4 and identify non-tryptic cleavage sites. CTSS digested rhPRG4 in a time and dose dependent manner. CTSS digestion of rhPRG4 at 1% (where % is the mass ratio of CTSS to rhPRG4) resulted in a time dependent decrease in the full-length, ~460 kDa, monomeric rhPRG4 band, and an appearance of lower MW fragments. After 20 h, no full-length rhPRG4 was observed. Furthermore, with an increased relative enzyme concentration of 3%, no protein bands were observed after 2 h, indicating complete digestion of rhPRG4. Western blotting demonstrated PRG4 is present in normal human tears, and that rhPRG4, tears, and tears supplemented with rhPRG4 incubated with 3–9% CTSS demonstrated decreased intensity of high MW PRG4 bands, indicative of partial degradation by CTSS. Similarly, western blotting of PRG4 in SS tears incubated with CTSS demonstrated decreased intensity of high MW PRG4 bands, which was reversed in the presence of the CTSS inhibitor. CTSS treatment of rhPRG4 resulted in an increased friction coefficient, compared to untreated controls. Lastly, the lower MW bands were confirmed to be PRG4 fragments by tandem mass spectrometry, and 6 non-tryptic cleavage sites were identified. rhPRG4 is susceptible to proteolytic digestion by CTSS, both alone and in human tears, which results in diminished ocular surface boundary lubricating ability. Moreover, endogenous PRG4 is susceptible to proteolytic digestion by CTSS, both in normal and SS tears. Given the elevated activity of CTSS in SS tears, and the role intact PRG4 plays in ocular surface health and lubrication, degradation of PRG4 by CTSS is a potential mechanism for diminished ocular surface lubrication in SS. Collectively these results suggest that tear supplementation of PRG4 may be beneficial for SS patients. © 2017 Elsevier Ltd

Stapleton,F., Alves,M., Bunya,V. Y., Jalbert,I., Lekhanont,K., Malet,F., Na,K. -S, Schaumberg,D., Uchino,M., Vehof,J., Viso,E., Vitale,S., Jones,L. TFOS DEWS II Epidemiology Report Ocular Surface 2017;15(3):334-365 [ Show Abstract ]

The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.

Sullivan,D. A., Rocha,E. M., Aragona,P., Clayton,J. A., Ding,J., Golebiowski,B., Hampel,U., McDermott,A. M., Schaumberg,D. A., Srinivasan,S., Versura,P., Willcox,M. D. P. TFOS DEWS II Sex, Gender, and Hormones Report Ocular Surface 2017;15(3):284-333 [ Show Abstract ]

One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs). In addition to sex, gender also appears to be a risk factor for DED. “Gender” and “sex” are words that are often used interchangeably, but they have distinct meanings. “Gender” refers to a person's self-representation as a man or woman, whereas “sex” distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health. Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED. © 2017 Elsevier Inc.

Willcox,M. D. P., Argüeso,P., Georgiev,G. A., Holopainen,J. M., Laurie,G. W., Millar,T. J., Papas,E. B., Rolland,J. P., Schmidt,T. A., Stahl,U., Suarez,T., Subbaraman,L. N., Uçakhan,O. Ö., Jones,L. TFOS DEWS II Tear Film Report Ocular Surface 2017;15(3):366-403 [ Show Abstract ]

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

Wolffsohn,J. S., Arita,R., Chalmers,R., Djalilian,A., Dogru,M., Dumbleton,K., Gupta,P. K., Karpecki,P., Lazreg,S., Pult,H., Sullivan,B. D., Tomlinson,A., Tong,L., Villani,E., Yoon,K. C., Jones,L., Craig,J. P. TFOS DEWS II Diagnostic Methodology report Ocular Surface 2017;15(3):539-574 [ Show Abstract ]

The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

2016

Berntsen,D. A., Hickson-Curran,S. B., Jones,L. W., Mathew,J. H., Maldonado-Codina,C., Morgan,P. B., Schulze,M. M., Nichols,J. J. Subjective comfort and physiology with modern contact lens care products Optometry and Vision Science 2016;93(8):809-819 [ Show Abstract ]

Purpose. To compare subjective comfort and ocular physiology with three multipurpose solutions (MPSs) to that of a peroxide-based system with three different soft contact lens materials. Methods. Habitual soft contact lens wearers (n = 236) were enrolled at three sites and completed a washout period with no contact lens solution for =4 days. Subjects were randomly assigned to one of three lens types: etafilcon A, galyfilcon A, or senofilcon A. A new lens of the assigned type was worn for 10 to 14 days each while using one of four care solutions, in random order (A - polyaminopropyl biguanide + polyquaternium, B - POLYQUAD + Aldox, C - alexidine + polyquaternium-1, and D - hydrogen peroxide) with a washout period (=4 days) between each solution. After each care solution, biomicroscopy was performed and subjective comfort was assessed using the Contact Lens User Experience (CLUE) questionnaire and other instruments including comfortable wear time (CWT). Linear mixed models were used for analysis. Comfort and biomicroscopy signs with each MPS were compared to that of the peroxide solution. Results. Subjective CLUE Comfort score across all lens types with each MPS was not significantly different than with the peroxide solution (p = 0.98). There were no differences in CWT between each MPS and the peroxide solution for any lens type (range of differences: -0.8 to 0.8 h; all p = 0.13). Six MPS/material combinations had no clinically meaningful change in corneal staining versus peroxide (<0.5 units); three combinations could increase staining by up to 0.57 units. Staining was <grade 1 for all combinations. Conclusions. Comparable levels of comfort were found between the latest generation of MPSs compared to peroxide disinfection. Three MPS/material combinations tested could result in increased corneal staining of up to 0.57 units versus a peroxide solution. Overall, these data suggest the care systems investigated are generally appropriate for usewith the contact lenses tested. © Copyright 2016 American Academy of Optometry.

Caffery,B., Dogru,M., Jones,L. W., Lin,M. C., Nichols,J. J., Papas,E., Pucker,A., Pult,H., Willcox,M. D. P. Contact lens comfort Optometry and Vision Science 2016;93(8):790-792

Cox,S. M., Berntsen,D. A., Chatterjee,N., Hickson-Curran,S. B., Jones,L. W., Moezzi,A. M., Morgan,P. B., Nichols,J. J. Eyelid margin and meibomian gland characteristics and symptoms in lens wearers Optometry and Vision Science 2016;93(8):901-908 [ Show Abstract ]

Purpose. To describe the lid margin characteristics of contact lens wearers and relate them to comfort during lens wear. Methods. Three study sites enrolled habitual contact lens wearers. Subjects completed the Comfort domain of the Contact Lens User Experience (CLUE) questionnaire, and each eye was graded for the presence of mucocutaneous junction (MCJ) displacement, lid margin irregularity, and lid margin vascularity. Examiners counted the number of meibomian gland (MG) orifices in the central centimeter of the lower eyelid and the number of those that showed pouting/plugging and vascular invasion. MG expressibility was graded according to the Shimazaki schema. Subjects were grouped based on presence/ absence of each characteristic, total number of orifices (=5 vs. 0). Descriptive statistics are reported. A linear model was used to assess the fixed effect of each characteristic on combined CLUE score and each CLUE statement, if the effect on combined CLUE score showed p < 0.10. Results. The study included 203 subjects (67.5% female) with mean age (±SD) of 30.3 ± 9.6 years. The most commonly observed characteristics were orifice pouting/plugging, compromised MG expressibility, and lid margin vascularity (35.0, 30.3, and 20.4%, respectively). MCJ displacement and MG expressibility had an effect on the combined CLUE score such that individual CLUE statements were analyzed (p = 0.01 and p = 0.06, respectively). MCJ displacement had an effect on comfort upon insertion (p = 0.01), comfort after 5 minutes (p = 0.03), end-of-day comfort (p = 0.01), and ability to maintain ocular moisture (p = 0.030). MG expressibility had a significant effect on general comfort (p = 0.01), comfort throughout the day (p = 0.02), and the ability to maintain ocular moisture (p = 0.02). Conclusions. MCJ displacement and MG expressibility have an effect on contact lens comfort. © Copyright 2016 American Academy of Optometry.

Dantam,J., McCanna,D. J., Subbaraman,L. N., Papinski,D., Lakkis,C., Mirza,A., Berntsen,D. A., Morgan,P., Nichols,J. J., Jones,L. W. Microbial contamination of contact lens storage cases during daily wear use Optometry and Vision Science 2016;93(8):925-932 [ Show Abstract ]

Purpose. To evaluate contact lens (CL) storage case contamination when used with four different CL care solutions during daily wear of three different CL materials. Methods. A parallel, prospective, bilateral, randomized clinical trial (n = 38) was conducted. Subjects were randomly assigned to use one of three CL materials (etafilcon A, senofilcon A, or galyfilcon A) on a daily wear basis. Subsequently, each subject randomly used one of four different CL care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and CLEAR CARE) for 2 weeks, along with their respective storage cases. After every 2-week period, their storage cases were collected and the right and left wells of each storage case were randomized for two procedures: (1) microbial enumeration by swabbing the storage case surface and (2) evaluation of biofilm formation (multipurpose solution cases only) using a crystal violet staining assay. Results. More than 80% of storage cases were contaminated when used in conjunction with the four CL care solutions, irrespective of the CL material worn. Storage cases maintained with CLEAR CARE (mean Log colony forming units (CFU)/ well ± SD, 2.0 ± 1.0) revealed significantly (p < 0.001) greater levels of contamination, compared to those maintained with Biotrue (1.3 ± 0.8) and RevitaLens OcuTec (1.2 ± 0.8). Predominantly, storage cases were contaminated with Gram-positive bacteria (= 80%). There were significant differences (p = 0.013) for the levels of Gram-negative bacteria recovered from the storage cases maintained with different CL care solutions. Storage cases maintained withOPTI-FREE PureMoist (0.526 ± 0.629) showed significantly higher biofilm formation (p = 0.028) compared to those maintained with Biotrue (0.263 ± 0.197). Conclusions. Levels of contamination ranged from 0 to 6.4 Log CFU/storage case well, which varied significantly (p < 0.001) between different CL care solutions, and storage case contamination was not modulated by CL materials. © Copyright 2016 American Academy of Optometry.

Hall,B., Heynen,M., Jones,L. W., Forrest,J. A. Analysis of Using I125 Radiolabeling for Quantifying Protein on Contact Lenses Current eye research 2016;41(4):456-465 [ Show Abstract ]

Purpose: To investigate the accuracy of I125 radiolabeling to quantitatively determine the deposition of protein onto various commercially available contact lens (CL) materials. Methods: Commercially available silicone hydrogel and conventional hydrogel CL materials were examined for times ranging from 10 s to 1 week. Adsorption of free I125 was measured directly for the CL. The use of dialyzing labeled proteins and/or using NaI to compete with free I125 uptake was investigated as ways to minimize effects due to free I125. Results: At all time points and with all lens materials, there was 0.3 µg/lens or greater of apparent mass attributable to free I125 uptake. Dialyzing labeled proteins significantly reduced free I125 uptake for all materials investigated. The benefit of using dialyzed protein was most prominent at shorter times, as free I125 is continuously generated over time. Using NaI can reduce free I125 uptake for some lens materials, but this is shown to directly affect protein deposition on some materials. Conclusions: Periodic replenishment of incubation solutions with freshly dialyzed labeled protein to limit free I125 generation is recommended, but the incorporation of NaI onto the buffer solution is not. Irrespective of the exact procedure to limit free I125 uptake, extra steps must be performed to quantify the amount of I125 adsorbed onto contact lens materials, to determine thresholds of confidence with respect to the actual protein deposition that occurs.

Jones,D., Woods,C., Jones,L., Efron,N., Morgan,P. A sixteen year survey of Canadian contact lens prescribing Contact Lens and Anterior Eye 2016;39(6):402-410 [ Show Abstract ]

Purpose To understand long-term contact lens prescribing habits of Canadian optometrists. Methods One thousand optometrists were surveyed annually from 2000 to 2015. Information was requested on the first ten patients examined after receiving the survey. Results Over the 16-year survey period, 1987 optometrists provided information on 19,143 patients. Mean age of the patients was 32.7 ± 14.4 years. Ratio of females to males was 2:1, the ratio of new fits to refits was 2:3. Soft contact lenses represented 94.5% of all fits. Rigid lenses were more often used as a refit compared to a new fit. Over the 16 years, market share for silicone hydrogel materials grew from 0% to 69.6%, mid-water content materials declined from 75.7% to 14.1%. The multifocal market share grew at the expense of spherical designs, with no change in toric lens fitting. Monthly soft lens replacement remained the preferred option at 48.2%, followed by daily disposable at 40.8%; two-weekly replacement declined to less than10% of patients by 2015. Extended wear was likely used to refit and only to a small proportion of wearers, representing 2.6% of SCL by 2015. The lens care system of choice throughout the period was multipurpose solutions, although the proportion for peroxide systems more than doubled by 2015 from 9.6%, to 21.1%. Conclusions Over the 16-year period, SCL material preference changed to silicone hydrogels with monthly replacement being preferred; daily disposables replacing 2-weekly as the alternate. Lens care preference continued to be multipurpose solutions. Rigid lenses appear to be sustained for specialist fitting. © 2016 British Contact Lens Association

Jones,L. W., Byrne,M., Ciolino,J. B., Legerton,J., Markoulli,M., Papas,E., Subbaraman,L. Revolutionary future uses of contact lenses Optometry and Vision Science 2016;93(4):325-327

Jones,L., Chauhan,A.,DiGirolamo,N., Sheedy,J., Smith III,E. Expert views on innovative future uses for contact lenses Optometry and Vision Science 2016;93(4):328-35 [ Show Abstract ]

Over the past 10 to 15 years, the availability of new materials and technologies has resulted in revolutionary concepts for contact lenses being proposed that go well beyond correcting vision. These novel uses include their prescribing to deliver topical ocular and systemic drugs, assist with ocular surface disease management, and limit the progression of myopia and novel methods to display visual information. How likely are these concepts to become commercially available, how successful will they be, and what are the potential issues to consider for them to come to market? To answer these questions, a panel of four experts were invited to discuss the benefits and pitfalls of these technologies and what challenges lay ahead of these concepts before their availability. Their responses provide a fascinating insight for the clinician into the likelihood of such revolutionary contact lenses being available in a clinical setting.

Keir,N., Luensmann,D., Woods,C.A., Bergenske,P., Fahmy,M., Fonn,D. Effect of Masking on Subjective Responses to Daily Disposable Contact Lenses Optom Vis Sci 2016;93(8):828-35 [ Show Abstract ]

PURPOSE: To explore the effect of masking on subjective responses when wearing daily disposable (DD) contact lenses.
METHODS: In an adaptation phase, habitual wearers of Manufacturer-A (MFA) (n = 43) and Manufacturer-B (MFB) (n = 53) wore MFA-brand 1 or MFB-brand 1 DDs, respectively, for 30 days, open-label. Subjects were then randomly assigned to one of two experiments. Each experiment included two, 3-day crossover phases. An enhanced version of MFA and MFB lenses (MFA-brand 2 and MFB-brand 2) were worn contralaterally to evaluate potential differences in masking result between manufacturers. Experiment 1: subjects were fully masked to lens and packaging (FM) then unmasked (UM). Experiment 2: subjects were FM then partially masked using an over-label (PM). Comfort ratings (0-100) were recorded for each lens daily and preference between lenses was recorded on day 3 for each crossover phase. The mean difference between 0-100 ratings or preference when FM or PM versus UM for the same lens was considered a measurement of the effect associated with masking. The purpose of the study was withheld from subjects to minimize bias.
RESULTS: The effect associated with masking for habitual wearers of MFA and MFB lenses was less than 1 out of 100 (0 ± 2.5) in both experiments. Fifty-eight subjects (60%) expressed no preference when FM. This decreased to 29 (30%) when UM or PM (proportion test, p < 0.001). Approximately half the subjects had a change in lens preference when they were UM or PM, primarily in favor of their habitual lens manufacturer.
CONCLUSIONS: Masking did not have a measurable impact on 0-100 ratings with the DD lenses used in this study but did have an impact on lens preference. Subjects were more likely to express a preference when they handled the lenses and were exposed to the lens packaging and, in some cases, able to read the lens brand and lens manufacturer.

Liu,L. Y., Seo,J., McCanna,D. J., Subbaraman,L. N., Jones,L. W. Assessment of biofilm formation of E. meningoseptica, D. acidovorans, and S. maltophilia in lens cases and their growth on recovery media Contact Lens and Anterior Eye 2016;39(2):117-123 [ Show Abstract ]

Purpose: Bacterial biofilm formation in contact lens cases is a risk factor in the development of both microbial and infiltrative keratitis. This investigation evaluated three emerging pathogens: Stenotrophomonas maltophilia, Elizabethkingia meningoseptica, and Delftia acidovorans for biofilm formation and metabolic activity in lens cases. Also, growth of these bacteria on different media was assessed to optimize recovery conditions. Methods: The three bacteria were incubated in lens cases with different concentrations of tryptic soy broth. Biofilm formation was evaluated by measuring metabolic activity using MTT and enumerating the number of viable bacteria. To determine the optimal recovery media, dilutions of these microorganisms were plated on six different media. The number of colony forming units (CFU) was recorded after 48, 72, and 96 h of incubation at 32 °C and 37 °C for S. maltophilia, and at 37 °C for E. meningoseptica and D. acidovorans. Results: All three microorganisms established biofilms in the lens cases, with significant numbers of CFU recovered. Biofilms of S. maltophilia and E. meningoseptica were metabolically active. Significant reduction in metabolic activity and number of viable S. maltophilia occurred when the incubation temperature was raised from 32 °C to 37 °C (p < 0.05). The metabolic activity of the biofilms increased with greater organic load present. The highest percent recovery for all three organisms was given by Columbia blood agar, followed by chocolate. Conclusion: Based on the results, the presence of the three emerging pathogens present in lens cases and from corneal isolates can be accurately determined if proper growth media and incubation temperatures are utilized.

Liu,S., Dozois,M. D., Chang,C. N., Ahmad,A., Ng,D. L. T., Hileeto,D., Liang,H., Reyad,M. -M, Boyd,S., Jones,L. W., Gu,F. X. Prolonged ocular retention of mucoadhesive nanoparticle eye drop formulation enables treatment of eye diseases using significantly reduced dosage Molecular Pharmaceutics 2016;13(9):2897-2905 [ Show Abstract ]

Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance. © 2016 American Chemical Society.

Moezzi,A. M., Varikooty,J., Schulze,M., Ngo,W., Lorenz,K. O., Boree,D., Jones,L. W. Corneal Swelling with Cosmetic etafilcon A Lenses versus No Lens Wear Optometry and Vision Science 2016;93(6):619-628 [ Show Abstract ]

Purpose: To determine if the use of pigments or adding polyvinyl pyrrolidone during the fabrication of 1-DAY ACUVUE DEFINE (AD) brand contact lenses impacts open-eye corneal swelling compared with no lens wear (NLW). Methods: A partial double-masked, randomized, bilateral crossover study was conducted in 24 Asian subjects using AD, 1-DAY ACUVUE DEFINE with Lacreon (ADL), NLW, and a control lens with no tint (1-DAY ACUVUE MOIST [AM]). Central corneal thickness was measured before insertion and immediately after removal after 8 ± 1 h of open-eye wear using an optical pachymeter in one eye. Corneal thickness along a 10-mm cord was measured in the contralateral eye using the Visante optical coherence tomographer (OCT). Corneal swelling was tested for noninferiority using a 5% margin. The endothelial bleb response was measured at baseline and 20 min after lens insertion using specular microscopy. Subjective grading of corneal staining and limbal/bulbar hyperemia were also monitored. Results: After 8 ± 1 h of open-eye wear, central corneal swelling across the study lenses with either optical pachymeter or OCT methods was negligible. Peripheral corneal swelling least-square mean differences with OCT were -0.03% (95% confidence interval [95% CI], -0.65 to 0.58%) and -0.26% (95% CI, -0.87 to 0.36%) between AD and ADL and the control lens (AM), respectively, and 1.67% (95% CI, 1.06 to 2.29%) and 1.45% (95% CI, 0.84 to 2.06%) between AD and ADL and NLW, respectively. No endothelial blebs were observed. No clinically significant differences were distinguished between the lenses and NLW for corneal staining and limbal/bulbar hyperemia. Conclusions: After 8 ± 1 h of open-eye wear, central and peripheral corneal swelling along the horizontal meridian with AD, ADL, AM, and NLW were equivalent. These results confirm that the addition of polyvinyl pyrrolidone or pigments to etafilcon A to obtain a limbal ring design have no impact on corneal swelling or limbal/bulbar hyperemia during normal open-eye wear.

Muntz,A., van Doorn,K., Subbaraman,L. N., Jones,L. W. Impression cytology of the lid wiper area Journal of Visualized Experiments 2016 (114): [ Show Abstract ]

Few reports on the cellular anatomy of the lid wiper (LW) area of the inner eyelid exist and only one report makes use of cytological methods. The optimization of a method of collecting, staining and imaging cells from the LW region using impression cytology (IC) is described in this study. Cells are collected from the inner surface of the upper eyelid of human subjects using hydrophilic polytetrafluoroethylene (PTFE) membranes, and stained with cytological dyes to reveal the presence of goblet cells, mucins, cell nuclei and various degrees of pre- and parakeratinization. Immunocytochemical dyes show cell esterase activity and compromised cell membranes by the use of a confocal scanning laser microscope. Up to 100 microscopic digital images are captured for each sample and stitched into a high-resolution, large scale image of the entire IC span. We demonstrate a higher sensitivity of IC than reported before, appropriate for identifying cellular morphologies and metabolic activity in the LW area. To our knowledge, this is the first time this selection of fluorescent dyes was used to image LW IC membranes. This protocol will be effective in future studies to reveal undocumented details of the LW area, such as assessing cellular particularities of contact lens wearers or patients with dry eye or lid wiper epitheliopathy. © 2016 Journal of Visualized Experiments.

Ng,A., Evans,K., North,R. V., Jones,L., Purslow,C. Impact of Eye Cosmetics on the Eye, Adnexa, and Ocular Surface Eye and Contact Lens 2016;42(4):211-220 [ Show Abstract ]

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film. © 2015 Contact Lens Association of Ophthalmologists.

Omali,N. B., Heynen,M., Subbaraman,L. N., Papinski,D., Lakkis,C., Smith,S. L., Morgan,P. B., Berntsen,D. A., Nichols,J. J., Jones,L. W. Impact of lens care solutions on protein deposition on soft contact lenses Optometry and Vision Science 2016;93(8):963-972 [ Show Abstract ]

Purpose. To evaluate the effect of four contemporary lens care solutions on total protein, total lysozyme, and active lysozyme extracted from three contact lens materials. Methods. Adapted contact lens wearers were recruited at three sites, and all subjects were randomly assigned to daily wear of either etafilcon A, galyfilcon A, or senofilcon A for 2 weeks. Four lens care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and ClearCare) were used by each subject in random order with a new pair of lenses after a washout period between solutions of at least 4 days. After 2 weeks of daily wear, contact lenses were collected for analysis. Proteins were extracted from a subset of contact lenses (n = 568) and total protein, total lysozyme, and lysozyme activity were quantified using a modified Bradford assay, an enzyme-linked immunosorbent assay, and a micrococcal assay, respectively. Results. Higher levels of total protein were extracted from etafilcon A when used with Biotrue compared to other solutions (p = 0.0001). There were higher levels of total lysozyme extracted from galyfilcon A lenses when used with PureMoist than with Biotrue or Clear Care (p < 0.006). Higher total lysozyme was extracted from senofilcon A when used with RevitaLens OcuTec compared to Biotrue (p = 0.002). Lower lysozyme activity was recovered from senofilcon A lenses with RevitaLens OcuTec when compared to all other care solutions (all p < 0.004). When Biotrue, PureMoist, or RevitaLens OcuTec were used, higher total lysozyme was extracted from galyfilcon A compared to senofilcon A(p < 0.01). When RevitaLens OcuTec was used, higher levels of active lysozyme were extracted from galyfilcon A compared to senofilcon A (p = 0.02). Conclusions. The ability of lens care solutions to remove protein from lenses varies depending upon the care solution composition and also the polymeric make-up of the contact lens material. © Copyright 2016 American Academy of Optometry.

Phan,C. -M, Bajgrowicz-Cieslak,M., Subbaraman,L. N., Jones,L. Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing Transl Vis Sci Technol. 2016;5(6):3 [ Show Abstract ]

PURPOSE: The aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model.
METHODS: Four commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device.
RESULTS: Overall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05).
CONCLUSIONS: Moxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased.
TRANSLATIONAL RELEVANCE: Results suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials.

Phan,C. -M, Bajgrowicz,M., Gao,H., Subbaraman,L. N., Jones,L. W. Release of fluconazole from contact lenses using a novel in vitro eye model Optometry and Vision Science 2016;93(4):387-394 [ Show Abstract ]

Purpose. Rapid drug release followed by a plateau phase is a common observation with drug delivery from contact lenses (CLs) when evaluated in a vial. The aim of this study was to compare the release of fluconazole from seven commercially available daily disposable CLs using a conventional vial-based method with a novel in vitro eye model. Methods. An eye model was created using two 3-dimensional printed molds, which were filled with polydimethylsiloxane to obtain an inexpensive model that would mimic the eyeball and eyelid. The model was integrated with a microfluidic syringe pump, and the flow-through was collected in a 12-well microliter plate. Four commercial daily disposable conventional hydrogels (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three silicone hydrogels (somofilcon A, narafilcon A, delefilcon A) were evaluated. These CLs were incubated with fluconazole for 24 h. The drug release was measured in a vial containing 4.8 mL of phosphate-buffered saline and in the polydimethylsiloxane eye model with a 4.8-mL tear flow across 24 h. Results. Overall, conventional hydrogel CLs had a higher uptake and release of fluconazole than silicone hydrogel CLs (p < 0.05). A higher drug release was observed in the vial condition compared with the eye model (p < 0.001). In the vial system, the drugs were rapidly released from the CL within the first 2 h, followed by a plateau phase. In contrast, drug release in the eye model under low tear volume was sustained and did not reach a plateau across 24 h (p < 0.05). Conclusions. Rapid drug release results from using a vial as the release system. Under low tear volume at physiological tear flow, commercial CLs can maintain a sustained drug release profile for up to 24 h. However, eyes with fungal keratitis may have increased tearing, which would significantly accelerate drug release. © 2015 American Academy of Optometry.

Phan,C. -M, Bajgrowicz,M., McCanna,D. J., Subbaraman,L. N., Jones,L. Effects of Antifungal Soaked Silicone Hydrogel Contact Lenses on Candida albicans in an Agar Eye Model Eye and Contact Lens 2016;42(5):313-317 [ Show Abstract ]

Purpose: To evaluate the effects of two commercial silicone hydrogel contact lenses (CLs) soaked with natamycin (NA) or fluconazole (FL) on the growth of Candida albicans in an in vitro eye model. Methods: Three-D printed molds were used as a cast for making eye-shaped models comprising potato dextrose agar. Senofilcon A (SA) and lotrafilcon B (LB) CLs were incubated with either 2 mL of NA or FL at a concentration of 1 mg/mL for 24 hr. To simulate a fungal infection, the eye models were coated with C. albicans. The drug-soaked lenses were placed on top of the eye models. Seven experimental conditions were examined: (1) NA-SA, (2) NA-LB, (3) FL-SA, (4) FL-LB, (5) SA, (6) LB, and (7) control - no lens. At specified time points (t1, 8, 16, 24, 48 hr), the agar eyes from each experimental condition were removed from the incubator and photographed. The yeast cells from the 24 and 48 hr time point were also analyzed using light microscopy. Results: At 24 and 48 hr, there was considerable growth observed for all conditions except for the NA-SA and NA-LB conditions. When observed under the microscope at 24 and 48 hr, the morphology of the yeast cells in the FL-SA and SA condition were similar to that of the control (oval shaped). There was limited hyphae growth observed for LB and significant visible hyphae growth for the NA-LB group. For NA-SA, NA-LB, and FL-LB groups, the cells were significantly smaller compared with the control. Conclusions: For NA-SA and NA-LB, there was limited growth of C. albicans observed on the eye models even after 48 hr. Under the microscope, the cell morphology differ noticeably between each testing condition, and is dependent on drug-lens combinations. © 2015 Contact Lens Association of Ophthalmologists.

Phan,C. -M, Subbaraman,L., Jones,L. W. The use of contact lenses as biosensors Optometry and Vision Science 2016;93(4):419-425 [ Show Abstract ]

The tear film is a complex multilayer film consisting of various proteins, enzymes, and lipids and can express a number of biomarkers in cases of disease. The development of a contact lens sensor presents a noninvasive alternative for the detection and management of various diseases. Recent work has resulted in the commercialization of a device to monitor intraocular pressure for up to 24 h, and there are extensive efforts underway to develop a contact lens sensor capable of continuous glucose tear film monitoring to manage diabetes. This clinical perspective will highlight the major developments within this field and list some of the major challenges that still need to be addressed. © 2015 American Academy of Optometry.

Phan,C. -M, Walther,H., Gao,H., Rossy,J., Subbaraman,L. N., Jones,L. Development of an in Vitro ocular platform to test contact lenses Journal of Visualized Experiments 2016;2016(110):e53907 [ Show Abstract ]

Currently, in vitro evaluations of contact lenses (CLs) for drug delivery are typically performed in large volume vials,1-6 which fail to mimic physiological tear volumes.7 The traditional model also lacks the natural tear flow component and the blinking reflex, both of which are defining factors of the ocular environment. The development of a novel model is described in this study, which consists of a unique 2-piece design, eyeball and eyelid piece, capable of mimicking physiological tear volume. The models are created from 3-D printed molds (Polytetrafluoroethylene or Teflon molds), which can be used to generate eye models from various polymers, such as polydimethylsiloxane (PDMS) and agar. Further modifications to the eye pieces, such as the integration of an explanted human or animal cornea or human corneal construct, will permit for more complex in vitro ocular studies. A commercial microfluidic syringe pump is integrated with the platform to emulate physiological tear secretion. Air exposure and mechanical wear are achieved using two mechanical actuators, of which one moves the eyelid piece laterally, and the other moves the eyeballeyepiece circularly. The model has been used to evaluate CLs for drug delivery and deposition of tear components on CLs.

Schulze,M. -M, Srinivasan,S., Hickson-Curran,S. B., Berntsen,D. A., Howarth,G. F., Toubouti,Y., Morgan,P., Nichols,J. J., Jones,L. W. Lid wiper epitheliopathy in soft contact lens wearers Optometry and Vision Science 2016;93(8):943-954 [ Show Abstract ]

Purpose. To evaluate lid wiper epitheliopathy (LWE) in soft contact lens (SCL) wearers on initial presentation and after using various SCL and solution combinations. Methods. LWE was assessed in 253 habitual SCL wearers who attended a screening visit at one of three study sites. LWE was assessed using lissamine green and sodium fluorescein dyes (Korb scale); a final LWE grade was calculated as the averaged LWE grade of the two dyes. Eligible habitual wearers continued into the four study periods, during which they wore one of three SCL types (etafilcon A, galyfilcon A, or senofilcon A) while using each of four care solutions for 10 to 14 days in randomized order. Statistical analyses were performed using linear mixed models, testing for differences in LWE for subject characteristics and between three multipurpose (MPS) test solutions (BioTrue, OPTI-FREE PureMoist, RevitaLens OcuTec) compared to a hydrogen peroxide (Clear Care) control solution. Results. LWE was present in 85% of habitual SCL wearers. LWE was not different for age (p = 0.28), sex (p = 0.99), race (p = 0.34), and comfort (p = 0.38) and not correlated with refractive error (r = 0.07). LWE was lower in habitual senofilcon A wearers (least-squares (LS) mean ± SE = 0.82 ± 0.19) compared to wearers of lotrafilcon B (1.34 ± 0.20; p < 0.02), comfilcon A (1.41 ± 0.21; p < 0.01), and other (1.18 ± 0.16; p < 0.03). Two hundred three participants completed all four study solutions with their assigned lens type; LWE was not different between the MPSs compared to the peroxide control solution across lens materials, except for less LWE for BioTrue (0.88 ± 0.17) versus Clear Care for participants wearing galyfilcon A (1.11 ± 0.18; p < 0.01). Conclusions. On initial presentation, LWE was present in 85% of habitual wearers and found to be independent of age, sex, race, comfort, and refractive error but dependent on habitual SCL type. There were no clinically meaningful differences in LWE between the MPSs and hydrogen peroxide solution for the three lens types studied. © Copyright 2016 American Academy of Optometry.

Stahl,U., Keir,N. J., Landers,A., Jones,L. W. Effect of short recovery periods on ocular comfort during daily lens wear Optometry and Vision Science 2016;93(8):861-871 [ Show Abstract ]

Purpose. To assess the impact of lens-free intervals of varying lengths on end-of-day comfort with soft contact lenses. Methods. Twenty-five symptomatic lens wearers participated in this randomized, cross-over study involving nine individual 12-hour days: one spectacle (no lens) and eight lens wear days. On each lens wear day, lenses were worn bilaterally in 2-hour intervals, separated by lens-free (recovery) periods of 0, 30, 60, or 80 minutes (repeated throughout the day). For each 2-hour lens wear interval, new lenses were worn. Ocular comfort was rated on a 0 to 100 visual analogue scale (0 = extremely uncomfortable); tear film and ocular parameters were assessed at the beginning and end of each study day. This study involved two different types of silicone hydrogel lenses, and the order of lens type and length of recovery period was randomized. Participants were unaware of the true study purpose and that a new lens pair was used for each lens wear interval. Results. End-of-day comfort on lens wear days was significantly worse than on the spectacle day (p 0.05). Although lens wear affected noninvasive tear film break-up time and conjunctival staining, there were no effects of recovery period length on noninvasive tear film break-up time (p > 0.05), tear meniscus height (p > 0.05), corneal staining (p > 0.05), conjunctival staining (p > 0.05), bulbar conjunctival redness (p > 0.05), or limbal redness (p > 0.05). There was no consistent effect of recovery period length on lid margin staining. Conclusions. Lens-free recovery periods during a 12-hour lens wear day did not positively impact end-of-day comfort in this study. Cumulative lens wear times ranged from 8 to 12 hours, and the results suggest that once the length of lens wear exceeds the usual comfortable wear time, there is no benefit of short recovery periods. © Copyright 2016 American Academy of Optometry.

Verma,M. S., Tsuji,J. M., Hall,B., Chen,P. Z., Forrest,J., Jones,L., Gu,F. X. Towards point-of-care detection of polymicrobial infections: Rapid colorimetric response using a portable spectrophotometer Sensing and Bio-Sensing Research 2016;1015-19 [ Show Abstract ]

Infectious diseases spread rapidly because current diagnostic methods are slow, expensive, and require technical expertise. Biosensors have recently been used as devices that can be deployed at the point-of-care for rapid and accurate diagnosis. Here, we show that a “chemical nose” biosensor based on gold nanoparticles can be coupled with a portable spectrophotometer to detect monomicrobial and polymicrobial solutions of pathogenic bacteria within 2 min of data collection. The design presented here exploits the rapid kinetics of gold nanoparticle aggregation around bacteria, which leads to a dramatic color change. The “chemical nose” produces unique signals based on the surface characteristics of the bacteria—such as the presence of extracellular polymeric substances, distribution of charged lipids, and localization of proteins—and hence provides a versatile platform for detection. We present a biosensor design that can easily be translated to the point-of-care because of its rapid response and simple output. © 2016 The Authors

Verma,M. S., Wei,S. -C, Rogowski,J. L., Tsuji,J. M., Chen,P. Z., Lin,C. -W, Jones,L., Gu,F. X. Interactions between bacterial surface and nanoparticles govern the performance of "chemical nose" biosensors Biosensors and Bioelectronics 2016;83:115-125 [ Show Abstract ]

Rapid and portable diagnosis of pathogenic bacteria can save lives lost from infectious diseases. Biosensors based on a "chemical nose" approach are attracting interest because they are versatile but the governing interactions between bacteria and the biosensors are poorly understood. Here, we use a "chemical nose" biosensor based on gold nanoparticles to explore the role of extracellular polymeric substances in bacteria-nanoparticle interactions. We employ simulations using Maxwell-Garnett theory to show how the type and extent of aggregation of nanoparticles influence their colorimetric response to bacteria. Using eight different species of Gram-positive and Gram-negative bacteria, we demonstrate that this "chemical nose" can detect and identify bacteria over two orders of magnitude of concentration (89% accuracy). Additionally, the "chemical nose" differentiates between binary and tertiary mixtures of the three most common hospital-isolated pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (100% accuracy). We demonstrate that the complex interactions between nanoparticles and bacterial surface determine the colorimetric response of gold nanoparticles and thus, govern the performance of "chemical nose" biosensors. © 2016 Elsevier B.V.

Walther,H., Subbaraman,L., Jones,L. W. In vitro cholesterol deposition on daily disposable contact lens materials Optometry and Vision Science 2016;93(1):36-41 [ Show Abstract ]

Purpose. The goal of this study was to analyze how various incubation times affect the uptake of cholesterol on silicone hydrogel (SH) and conventional hydrogel (CH) daily disposable (DD) contact lens materials using an in vitro radiochemical detectionmethod. Methods. Three SH (somofilcon A, delefilcon A, and narafilcon A) and four CH (etafilcon A, nesofilcon A, ocufilcon A, and nelfilcon A) contact lenses were incubated in an artificial tear solution that contained major tear film components and a portion of radioactive 14C-cholesterol. Lenses (N = 4) were incubated for four incubation times (2, 6, 12, or 16 h) to assess the effects on cholesterol deposition. Subsequent to the incubation, the lenses were extracted using 2:1 chloroform:methanol, and the extracts were analyzed in a beta counter and (in nanograms per lens) extrapolated from standard curves. Results. In general, cholesterol deposited statistically significantly more on SH lenses than CHs (p e 0.033), with the exception of somofilcon A and nesolfilcon A materials (p = 0.067). Within the SH materials, narafilcon A accumulated the largest quantity of cholesterol (p G 0.05) and somofilcon A the lowest (p G 0.05). The uptake of cholesterol ranged from 22.63 T 2.98 ng/lens to 97.94 T 4.18 ng/lens for all lens materials. The accumulation of cholesterol was shown to be continuous throughout the 16 h of incubation, without reaching a plateau (p G 0.001). Conclusions. For the periods thatDDlens materials are worn, cholesterol deposits significantlymore ontoSHcontact lenses than CHs. This could have implications for wearers who have higher levels of lipid in their tears that are fitted with SH DD materials. Copyright © American Academy of Optometry.

Wolffsohn,J. S., Calossi,A., Cho,P., Gifford,K., Jones,L., Li,M., Lipener,C., Logan,N. S, Malet,F., Matos,S., Meijome,J. M. G., Nichols,J .J., Orr, J.B., Santodomingo-Rubido,J., Schaefer,T., Thite,N., van der Worp,E., Zvirgzdina, M. Global trends in myopia management attitudes and strategies in clinical practice. Contact Lens and Anterior Eye 2016;39(2):106-116

Woods,J., Jones,L. W. Pilot study to determine the effect of lens and eye rinsing on Solution-Induced Corneal Staining (SICS) Optometry and Vision Science 2016;93(10):1218-1227 [ Show Abstract ]

Purpose The main purpose of this study was to determine whether two interventions (rinsing the lens before lens insertion and rinsing the ocular surface post-lens removal) had any impact on solution-induced corneal staining (SICS). In addition, the presence of hyper-reflective epithelial cells in the presence of SICS was investigated. Methods Twenty subjects wore new balafilcon A lenses, which had been soaked overnight in a multipurpose care product containing polyhexamethylene biguanide for 2 hours. The study was conducted across three phases. In phase 1 (investigator and subject masked, randomized eye), one lens was rinsed with nonpreserved saline before lens insertion. In phase 2 (investigator masked, randomized eye), one eye was rinsed with nonpreserved saline after lens removal, before staining assessment. Corneal staining was recorded as the percentage area of the cornea exhibiting superficial punctate staining. In both phases, ocular comfort and presence of specific symptoms were captured. In phase 3, there was no randomized treatment; confocal images of the epithelium were obtained after 2 hours of wear. Results In phase 1 (lens-rinse), there was no significant difference in staining between the treated and untreated eyes (84 vs. 92%, respectively; p = 0.06). In phase 2 (eye-rinse), there was also no significant difference between the treated and untreated eye (86 vs. 86%, p = 0.92). Most subjects were asymptomatic. In phase 3, images of hyper-reflective cells were captured in 97% of the eyes imaged. Conclusions The two rinsing procedures did not affect the level of the SICS response. Hyper-reflective epithelial cells were found to be present in a significant number of eyes exhibiting SICS, and their presence warrants further investigation. © 2016 American Academy of Optometry.

2015

Bajgrowicz,M., Phan,C. -M, Subbaraman,L. N., Jones,L. Release of ciprofloxacin and moxifloxacin from daily disposable contact lenses from an in vitro eye model Investigative Ophthalmology and Visual Science 2015;56(4):2234-2242 [ Show Abstract ]

Purpose. To analyze the release of two fluoroquinolones, ciprofloxacin and moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily disposable contact lenses (CLs), comparing release from a fixed-volume vial and a novel in vitro eye model. Methods. Four CH CLs (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A, delefilcon A) were used. The lenses were incubated in drug solutions for 24 hours. After the incubation period, the lenses were placed in two release conditions: (1) a vial containing 4.8 mL PBS for 24 hours and (2) an in vitro eye model with a flow rate at 4.8 mL over 24 hours. Results. Release in the vial for both drugs was rapid, reaching a plateau between 15 minutes and 2 hours for all lenses. In contrast, under physiological flow conditions, a constant and slow release was observed over 24 hours. The amounts of ciprofloxacin released from the lenses ranged between 49.6 ±0.7 and 62.8 ± 0.3 µg per lens in the vial, and between 35.0 ± 7.0 and 109.0 ± 5.0 µg per lens in the eye model. Moxifloxacin release ranged from 24.0 ± 4.0 to 226.0 ± 2.0 µg per lens for the vial, and between 13.0 ± 2.0 and 151.0 ± 10.0 µg per lens in the eye model. In both systems and for both drugs, HEMA-based CLs released more drugs than other materials. Conclusions. The parameters of the release system, in particular the volume and flow rate, have a significant influence on measured release profiles. Under physiological flow, release profiles are significantly slower and constant when compared with release in a vial. © 2015, The Association for Research in Vision and Ophthalmology, Inc.

Chang,J. M. L., McCanna,D. J., Subbaraman,L. N., Jones,L. W. Efficacy of antimicrobials against biofilms of achromobacter and pseudomonas Optometry and Vision Science 2015;92(4):506-513 [ Show Abstract ]

Purpose. Achromobacter xylosoxidans and Pseudomonas aeruginosa biofilms can develop in ophthalmic products and accessories such as contact lens cases, leading to the development of ocular infections. This study evaluated the efficacy of the antimicrobials polyaminopropyl biguanide (PAPB) and benzalkonium chloride (BAK) against A. xylosoxidans and P. aeruginosa biofilms. Methods. Biofilms of A. xylosoxidans and P. aeruginosa used as a comparative control were formed by incubating the bacteria on contact lens cases and on coverslips in phosphate-buffered saline. The biofilms were then exposed to PAPB and BAK for 5 minutes and 4 hours. After exposure, alginate swabs were used to remove the biofilms from the lens cases and the bacteria were plated on tryptic soy agar for determination of survivors. Also, after exposure to these disinfectants, the A. xylosoxidans and P. aeruginosa biofilms were stained with SYTO 9 and propidium iodide. Using a confocal microscope with a 488-nm laser, the number of cells with damaged cell membranes was determined. Results. After 5 minutes of exposure to BAK or PAPB, A. xylosoxidans biofilms were more resistant to the antimicrobial effects of these disinfectants than P. aeruginosa biofilms. After 4 hours, both organisms were reduced by more than 3 logs after exposure to either BAK or PAPB. Confocal microscopy studies revealed that BAK was more effective at damaging A. xylosoxidans and P. aeruginosa cell membranes than PAPB at the concentrations used in ophthalmic products. Conclusions. Biofilms of the emerging pathogen A. xylosoxidans were more resistant to the disinfectants PAPB and BAK than biofilms of P. aeruginosa. Because of the emergence of A. xylosoxidans and the demonstrated greater resistance to the common ophthalmic preservatives BAK and PAPB than the standard Gram-negative organism P. aeruginosa, A. xylosoxidans biofilms should be assessed in antimicrobial challenge tests to assure the safety of multiuse ophthalmic products. Copyright © 2015 American Academy of Optometry.

Guthrie,S. E., Jones,L., Blackie,C. A., Korb,D. R. A Comparative Study Between an Oil-in-Water Emulsion and Nonlipid Eye Drops Used for Rewetting Contact Lenses Eye and Contact Lens 2015;41(6):373-377 [ Show Abstract ]

OBJECTIVES: The purpose of this study was to determine the clinical impact of using SYSTANE BALANCE Lubricant Eye Drops (Alcon, Fort Worth, TX), an oil-in-water emulsion, as a rewetting eye drop in symptomatic contact lens wearers.
METHODS: Subjects who had previously experienced contact lens discomfort (CLD), with a mean lens wearing history of 18.6±12.8 years, were randomly assigned to use a Test (SYSTANE BALANCE Lubricant Eye Drops; n=76) or control (habitual nonlipid contact lens rewetting eye drop; n=30) drop over their contact lenses within 5 min of lens insertion and then subsequently at 2 hr intervals up to a maximum of 4 drops per eye daily for a 1-month period. Assessments of subjective comfort, comfortable wearing time, lid wiper epitheliopathy (LWE), and corneal staining were conducted at baseline and after 1 month, after 6 hr of lens wear.
RESULTS: Comfort, wearing time, LWE, and corneal staining all showed statistically significant improvements in the test group using SYSTANE BALANCE Lubricant Eye Drops at the 1-month visit compared with baseline data (all P<0.01) and compared with the control group at the 1-month visit (P<0.01, P=0.01, P<0.01, and P=0.03, respectively).
CONCLUSIONS: The use of SYSTANE BALANCE Lubricant Eye Drops as a rewetting drop in a group of wearers who experienced symptoms of CLD improved subjective comfort scores, increased comfortable wearing time, and reduced signs of LWE and corneal staining, when compared with the use of non–lipid-containing contact lens rewetting eye drops.

Hagedorn,S., Drolle,E., Lorentz,H., Srinivasan,S., Leonenko,Z., Jones,L. Atomic force microscopy and Langmuir-Blodgett monolayer technique to assess contact lens deposits and human meibum extracts Journal of Optometry 2015;8(3):187-199 [ Show Abstract ]

Purpose The purpose of this exploratory study was to investigate the differences in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface topography between participants with and without meibomian gland dysfunction (MGD). Methods Meibum study: Meibum was collected from all participants and studied via Langmuir-Blodgett (LB) deposition with subsequent Atomic Force Microscopy (AFM) visualization and surface roughness analysis. CL Study: Participants with and without MGD wore both etafilcon A and balafilcon A CLs in two different phases. CL lipid deposits were extracted and analyzed using pressure-area isotherms with the LB trough and CL surface topographies and roughness values were visualized using AFM. Results Meibum study: Non-MGD participant meibum samples showed larger, circular aggregates with lower surface roughness, whereas meibum samples from participants with MGD showed more lipid aggregates, greater size variability and higher surface roughness. CL Study: Worn CLs from participants with MGD had a few large tear film deposits with lower surface roughness, whereas non-MGD participant-worn lenses had many small lens deposits with higher surface roughness. Balafilcon A pore depths were shallower in MGD participant worn lenses when compared to non-MGD participant lenses. Isotherms of CL lipid extracts from MGD and non-MGD participants showed a seamless rise in surface pressure as area decreased; however, extracts from the two different lens materials produced different isotherms. Conclusions MGD and non-MGD participant-worn CL deposition were found to differ in type, amount, and pattern of lens deposits. Lipids from MGD participants deposited irregularly whereas lipids from non-MGD participants showed more uniformity. © 2014 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Hall,B., Jones,L. W., Forrest,J. A. Competitive effects from an artificial tear solution to protein adsorption Optometry and Vision Science 2015;92(7):781-789 [ Show Abstract ]

Purpose To compare the adsorption of lysozyme, lactoferrin, and albumin to various contact lens materials, between single-protein solutions and a multicomponent artificial tear solution (ATS). Additionally, extra steps were taken to distinguish loosely and tightly bound protein, the latter of which may be fully or partially denatured. Methods Using a previously described ATS, we measured the time-dependent adsorption of lys, lac, and alb onto one conventional hydrogel and four silicone hydrogel contact lens materials between the first minute and up to 1 week of protein interaction with the material surface. Proteins were quantified using I125 radiolabeling of each protein individually in ATS and buffered saline. Extra steps were taken to limit the amount of unbound I125 and to quantify the amount of reversibly bound protein. Results Comfilcon A, balafilcon A, and etafilcon A did not show any relevant competitive adsorption between the ATS components and lys, lac, or alb until after 1 week. Competitive adsorption effects for lys, lac, and alb were observed in as little as 1 minute on lotrafilcon B. Lotrafilcon B had no reversibly bound protein at any time points. The ionic materials balafilcon A and etafilcon A deposited significant amounts of reversibly bound lysozyme and lactoferrin in just 10 minutes. Senofilcon A apparent deposition was below our thresholds of confidence for this protein quantification method. Conclusions Both the competition between lys, lac, and alb and ATS components and the reversibility of these bound proteins is material specific. Coadsorption of lys, lac, and alb with ATS components can increase the reversibility of their adsorption. © 2015 American Academy of Optometry.

Hall,B., Jones,L., Forrest,J. A. Kinetics of competitive adsorption between lysozyme and lactoferrin on silicone hydrogel contact lenses and the effect on lysozyme activity Current eye research 2015;40(6):622-631 [ Show Abstract ]

To determine the effect of competitive adsorption between lysozyme and lactoferrin on silicone hydrogel contact lenses and the effect on lysozyme activity. Methods: Three commercially available silicone hydrogel contact lens materials (senofilcon A, lotrafilcon B and balafilcon A) were examined, for time points ranging from 10s to 2h. Total protein deposition was determined by I125 radiolabeling of lysozyme and lactoferrin, while the activity of lysozyme was determined by a micrococcal activity assay. Results: Senofilcon A and balafilcon A did not show any relevant competitive adsorption between lysozyme and lactoferrin. Lotrafilcon B showed reduced protein deposition due to competitive adsorption for lactoferrin at all time points and lysozyme after 7.5min. Co-adsorption of lactoferrin and lysozyme decreased the activity of lysozyme in solution for senofilcon A and lotrafilcon B, but co-adsorption had no effect on the surface activity of lysozyme for all lens types investigated. Conclusions: Competition between lysozyme and lactoferrin is material specific. Co-adsorption of lysozyme and lactoferrin does not affect the activity of surface-bound lysozyme but can reduce the activity of subsequently desorbed lysozyme. © 2015 Informa Healthcare USA, Inc.

Korogiannaki,M., Guidi,G., Jones,L., Sheardown,H. Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials. J Biomat Appl 2015;30(3):361-376

Liu,S., Chang,C. N., Verma,M. S., Hileeto,D., Muntz,A., Stahl,U., Woods,J., Jones,L. W., Gu,F. X. Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentallyinduced dry eye syndrome Nano Research 2015;8(2):621-635

Luensmann,D., Yu,M., Yang,J., Srinivasan,S., Jones,L. Impact of cosmetics on the physical dimension and optical performance of silicone hydrogel contact lenses Eye and Contact Lens 2015;41(4):218-227 [ Show Abstract ]

Objectives: To evaluate the impact of cosmetics on silicone hydrogel (SiHy) contact lens shape, lens power, and optical performance. Methods: In this in vitro experiment, 7 SiHy materials were coated with 9 marketed brands of cosmetics, including hand creams (HCs) (3), eye makeup removers (MRs) (3), and mascaras (3). Diameter, sagittal depth, and base curve were determined using the Chiltern (Optimec Limited), whereas lens power and optical performance were assessed using the Contest Plus (Rotlex). Six replicates were used for each lens and cosmetic combination.Measurements were repeated after a cleaning cycle using a one-step hydrogen peroxide solution. Results: Makeup removers had the greatest impact on diameter, sagittal depth, and base curve, resulting in changes of up to 0.5, 0.15, and 0.77 mm, respectively. The HCs and mascaras had little impact on these parameters; however, differences were observed between lens types. Optical performance was reduced with all mascaras, and a decrease of greater than 2 units on a 0 to 10 scale (10=uniform power distribution) was seen for 5 lens types exposed to waterproof mascara (P0.05). Lens cleaning resulted in some recovery of the lens parameters, and efficiency varied between cosmetics. Conclusion: Some eye MRs and waterproof mascaras changed the shape and optical performance of some SiHy lenses. Further research is needed to understand the clinical implications for SiHy lens wearers using cosmetics. © 2015 Contact Lens Association of Opthalmologists, Inc.

Menzies,Kara L., Srinivasan,Sruthi, Prokopich,C. Lisa, Jones,Lyndon Infrared Imaging of Meibomian Glands and Evaluation of the Lipid Layer in Sjögren's Syndrome Patients and Nondry Eye Controls Investigative ophthalmology & visual science 2015;56(2):836-841 [ Show Abstract ]

Purpose. The purpose of this study was to evaluate meibomian gland dropout and lipid layer thickness (LLT) in patients with and without Sjögren's syndrome dry eye (SS).Methods. We recruited 11 participants with SS (males/females [M/F], 1:10; mean age = 56.0 ± 9.1 years) and 10 control subjects without dry eye (M/F, 3:7; mean age = 58.5 ± 4.7 years). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The LLT was assessed using the Tearscope Plus based on the appearance of the lipid layer. Noninvasive tear break-up time (NITBUT) also was measured. The lower and upper lids were everted, and the meibomian glands were imaged using the infrared camera of the Keratograph 4. A meibomian gland dropout score due to gland loss was obtained. Statistical analysis was conducted using the Mann-Whitney U test and correlations were determined using Spearman rank correlations.Results. Of the SS participants, 100% reported ocular and oral dryness symptoms in the AECC questionnaire. The SS group recorded a higher OSDI score (median = 48.00, interquartile range [IQR] 23.0–56.2 vs. 2.1, IQR 0.0–2.6; P < 0.001), reduced LLT (median [IQR] = 15.0 [15.0–15.0] vs. 60.0 [45.0–100.0] nm; P = 0.001), and lower NITBUT (median [IQR] = 3.7 [2.5–4.2] vs. 9.5 [6.4–17.6] sec; P < 0.001) compared to the controls. Digital meibomian gland dropout score (% dropout) was significantly higher for the SS group (16.0% [IQR 12.1–40.0%] vs. 6.7% [IQR 1.5–12.7%]; P = 0.01). Subjective meibomian gland dropout score (0–6 score) was significantly higher for the SS group (median [IQR] = 1.5 [1.0–4.0] vs. 1.0 [0.0–1.25]; P = 0.03).Conclusions. Patients with SS showed higher meibomian gland dropout scores and reduced LLT and NITBUT, which likely contribute to the severe dry eye symptoms reported by SS subjects.

Moezzi,A. M., Fonn,D., Varikooty,J., Simpson,T. L. Overnight corneal swelling with high and low powered silicone hydrogel lenses Journal of Optometry 2015;8(1):19-26 [ Show Abstract ]

Purpose To compare central corneal swelling after eight hours of sleep in eyes wearing four different silicone hydrogel lenses with three different powers. Methods Twenty-nine neophyte subjects wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60) and senofilcon A (Dk, 103) lenses in powers -3.00, -10.00 and +6.00 D on separate nights, in random order, and on one eye only. The contra-lateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. Results For the +6.00 D and -10.00 D, lotrafilcon A induced the least swelling and galyfilcon A the most. The +6.00 D power, averaged across lens materials, induced significantly greater central swelling than the -10.00 and -3.00 D (Re-ANOVA, p < 0.001), (7.7 ± 2.9% vs. 6.8 ± 2.8% and 6.5 ± 2.5% respectively) but there was no difference between -10.00 and -3.00 D. Averaged for power, lotrafilcon A induced the least (6.2 ± 2.8%) and galyfilcon A the most (7.6 ± 3.0%) swelling at the center (Re-ANOVA, p < 0.001). Central corneal swelling with +6.00 D was significantly greater than -10.00 D lens power despite similar levels of average lens transmissibility of these two lens powers. Conclusions The differences in corneal swelling of the lens wearing eyes are consistent with the differences in oxygen transmission of the silicone hydrogel lenses. In silicone hydrogel lenses central corneal swelling is mainly driven by central lens oxygen transmissibility.

Muntz,A., Subbaraman,L. N., Sorbara,L., Jones,L. Tear exchange and contact lenses: A review Journal of Optometry 2015;8(1):2-11 [ Show Abstract ]

Tear exchange beneath a contact lens facilitates ongoing fluid replenishment between the ocular surface and the lens. This exchange is considerably lower during the wear of soft lenses compared with rigid lenses. As a result, the accumulation of tear film debris and metabolic by-products between the cornea and a soft contact lens increases, potentially leading to complications. Lens design innovations have been proposed, but no substantial improvement in soft lens tear exchange has been reported. Researchers have determined post-lens tear exchange using several methods, notably fluorophotometry. However, due to technological limitations, little remains known about tear hydrodynamics around the lens and, to-date, true tear exchange with contact lenses has not been shown. Further knowledge regarding tear exchange could be vital in aiding better contact lens design, with the prospect of alleviating certain adverse ocular responses. This article reviews the literature to-date on the significance, implications and measurement of tear exchange with contact lenses.

Ngo,W., Caffery,B., Srinivasan,S., Jones,L. W. Effect of lid debridement-scaling in sjögren syndrome dry eye Optometry and Vision Science 2015;92(9):e316-e320 [ Show Abstract ]

Purpose To evaluate the effect of lid debridement-scaling (LDS) on dry eye signs and symptoms in subjects with Sjögren syndrome (SS). Methods This prospective randomized controlled study enrolled 14 female subjects with SS. Seven subjects were randomized into the treatment group where they were selected to receive LDS; the remainder did not receive LDS and served as control subjects. Lid debridement-scaling was conducted using a stainless steel golf club spud (Hilco Wilson Ophthalmics, Plainville, MA) on both the upper and lower eyelids of both eyes. Outcome variables were assessed before LDS and again 1 month later. The outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) visual analog scores, ocular staining (SICCA OSS [Sjögren's International Collaborative Clinical Alliance Ocular Staining Score]), fluorescein tear breakup time (FLBUT), meibomian gland score (MGS), meibomian gland yielding liquid secretions (MGYLS) score, and line of Marx's (LOM) position. Results Thirteen subjects completed the study. Data from only the right eye were analyzed. For the control group (n = 6; mean [±SD] age, 62.3 [±11.6] years), the pre-LDS, post-LDS, and significance level (pre-LDS mean [±SD] vs. post-LDS mean [±SD]; p value) were as follows: OSDI (58.3 [±22.1] vs. 48.3 [±29.0]; p = 0.051), SANDE (77.4 [±22.1] vs. 89.6 [±32.6]; p = 0.20), SICCA OSS (7.0 [±4.5] vs. 8.2 [±3.5]; p = 0.25), MGS (1.3 [±1.5] vs. 1.0 [±0.9]; p = 0.75), MGYLS (0.3 [±0.5] vs. 0.0 [±0.0]; p = 0.50), FLBUT (2.99 [±1.54] vs. 2.85 [±1.79]; p = 0.63), and LOM (2.0 [±0.0] vs. 2.0 [±0.0]; p = n/a). For the treatment group (n = 7; mean [±SD] age, 58.0 [±8.1] years), the pre-LDS, post-LDS, and significance level were as follows: OSDI (63.2 [±13.3] vs. 46.9 [±19.4]; p = 0.04), SANDE (72.6 [±17.1] vs. 77.0 [±28.0]; p = 0.54), SICCA OSS (6.6 [±2.9] vs. 5.0 [±3.9]; p = 0.02), MGS (1.0 [±1.2] vs. 3.1 [±1.7]; p = 0.01), MGYLS (0.0 [±0.0] vs. 0.6 [±1.0]; p = 0.50), FLBUT (3.13 [±0.81] vs. 3.45 [±1.03]; p = 0.53), and LOM (0.9 [±0.9] vs. 1.0 [±1.0]; p = 1.00). Conclusions This pilot study showed that LDS improved symptoms, ocular staining, and meibomian gland function for the group that received LDS. This indicates that LDS can aid in the management of SS dry eye. © 2015 American Academy of Optometry.

Omali,N. B., Subbaraman,L. N., Coles-Brennan,C., Fadli,Z., Jones,L. W. Biological and clinical implications of lysozyme deposition on soft contact lenses Optometry and Vision Science 2015;92(7):750-757 [ Show Abstract ]

Within a few minutes of wear, contact lenses become rapidly coated with a variety of tear film components, including proteins, lipids, and mucins. Tears have a rich and complex composition, allowing a wide range of interactions and competitive processes, with the first event observed at the interface between a contact lens and tear fluid being protein adsorption. Protein adsorption on hydrogel contact lenses is a complex process involving a variety of factors relating to both the protein in question and the lens material. Among tear proteins, lysozyme is a major protein that has both antibacterial and anti-inflammatory functions. Contact lens materials that have high ionicity and high water content have an increased affinity to accumulate lysozyme during wear, when compared with other soft lens materials, notably silicone hydrogel lenses. This review provides an overview of tear film proteins, with a specific focus on lysozyme, and examines various factors that influence protein deposition on contact lenses. In addition, the impact of lysozyme deposition on various ocular physiological responses and bacterial adhesion to lenses and the interaction of lysozyme with other tear proteins are reviewed. This comprehensive review suggests that deposition of lysozyme on contact lens materials may provide a number of beneficial effects during contact lens wear. © 2015 American Academy of Optometry.

Pucker,A. D., Jones-Jordan,L. A., Li,W., Kwan,J. T., Lin,M. C., Sickenberger,W., Marx,S., Srinivasan,S., Jones,L. W. Associations with meibomian gland atrophy in daily contact lens wearers Optometry and Vision Science 2015;92(9):e206-e213 [ Show Abstract ]

Purpose To determine associations for contact lenses (CLs) and meibomian gland atrophy in a matched-pair study. Methods Contact lens wearers (case) and age- and sex-matched non-contact lens (NCL) wearers with no history of CL use (control) were recruited for a multicenter study. All subjects were administered the Ocular Surface Disease Index questionnaire and a comprehensive battery of clinical tests (e.g., tear breakup time, bulbar and limbal redness, meibography, etc.) were performed. Upper and lower eyelid meibomian gland atrophy were graded with both digital meibography (percent gland atrophy) and visual meiboscore methods. Conditional logistic regression analyses were then used to determine relationships among CL use, meibomian gland atrophy, and ocular surface signs and symptoms. Results A total of 70 matched pairs were analyzed. The mean (±SD) age of the CL group was 30.6 (±12.4) years, and that of the NCL group was 30.1 (±12.2) years. The subjects were 63% female. The association between CL wear and meiboscore was not significant univariately, but the best-fitting multivariate regression model showed that higher meiboscores were associated with being a CL wearer (odds ratio [OR], 2.45) in a model that included eyelid margin erythema (OR, 0.25) and lissamine green staining (OR, 1.25). Percent gland atrophy was not associated with CL wear in regression analysis (p = 0.31). Conclusions This study determined inconclusive associations with CLs and meibomian gland atrophy. This study also provided a comprehensive assessment of differences between CL and NCL wearers. © 2015 American Academy of Optometry.

Samsom,M., Chan,A., Iwabuchi,Y., Subbaraman,L., Jones,L., Schmidt,TA In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4) Tribology International 2015;89:27-33 [ Show Abstract ]

Contact lens friction was recently shown to correlate with in vivo comfort, with lower friction lenses providing improved comfort. Proteoglycan 4 (PRG4) is a recently discovered ocular surface boundary lubricant. The objectives of this study were to measure the friction of commercially available silicone hydrogel (SiHy) contact lenses against human cornea and eyelid tissues, and evaluate the ability of PRG4 to lubricate, and adhere to, SiHy contact lenses. The in vitro friction test employed here effectively measured and distinguished the SiHy contact lens friction coefficients against human eyelid and cornea tissues, and PRG4 functioned as an effective boundary lubricant.

Srinivasan,S., Otchere,H., Yu,M., Yang,J., Luensmann,D., Jones,L. Impact of cosmetics on the surface properties of silicone hydrogel contact lenses Eye and Contact Lens 2015;41(4):228-235 [ Show Abstract ]

Purpose: This study evaluated the impact of various cosmetics on the surface properties of silicone hydrogel (SiHy) contact lens materials. Methods: In this in vitro experiment, 7 SiHy contact lens materials were coated with 1 of 9 cosmetics, including common hand creams (3), eye makeup removers (3), and mascaras (3). Dark-field microscopy images were taken to determine pixel brightness (PB) after cosmetic exposure, which describes the visible surface deposition (n=6 for each lens type), with a higher PB indicating increased deposition. The sessile drop technique was used to determine the advancing contact angle (CA). Measurements were repeated for both methods after a single peroxide-based cleaning cycle. Results: Pixel brightness was significantly higher for mascara-coated lenses compared with the other cosmetic products (P,0.01). The peroxide-based lens care solution removed most deposits from the nonwaterproof mascara for 4 lens types, whereas deposits remained relatively unchanged for 1 waterproof mascara (P.0.05). Hand creams and makeup remover had minimal impact on PB. Changes in CA measurements after cosmetic application were highly lens dependent. Hand creams caused primarily a decrease in CA for 5 of the 7 lens types, whereas 1 of the waterproof mascaras caused a significant increase of 30 to 50° for 3 lens types. Conclusion: Some mascara-lens combinations resulted in increased CA and PB, which could have an impact on in vivo lens performance. Nonwaterproof mascara was mostly removed after a cleaning cycle. Further research is needed to understand the clinical implications for SiHy lens wearers using cosmetics. © 2015 Contact Lens Association of Opthalmologists, Inc.

Varikooty J., Srinivasan S., Subbaraman L., Woods C.A., Fonn D., Simpson T.L., Jones L.W. Variations in observable lid wiper epitheliopathy (LWE) staining patterns in wearers of silicone hydrogel lenses Contact Lens and Anterior Eye 2015;38(6):471-476

Varikooty,J., Schulze,M. M., Dumbleton,K., Keir,N., Woods,C. A., Fonn,D., Jones,L. W. Clinical performance of three silicone hydrogel daily disposable lenses Optometry and Vision Science 2015;92(3):301-311 [ Show Abstract ]

Purpose. To determine the clinical performance of DAILIES TOTAL1 (DT1), Clariti 1Day (C1D), and 1-DAY ACUVUE TruEye (AVTE) silicone hydrogel daily disposable contact lenses (SiHy DDCLs). Methods. Eligible participants, subdivided into asymptomatic and symptomatic groups, wore each SiHy DDCLs for three consecutive days. Each participant attended three visits (on day 1 at 0 hours; on days 1 and 3 after 8 hours ofwear) per lens type. The order of lens wear was randomized, with at least 1 day washout between lenses. Lens-related performance was evaluated by assessing lens surface deposits, wettability, pre-lens noninvasive tear breakup time, lens movement, and centration; ocular response assessments included conjunctival redness, corneal staining, and conjunctival staining and indentation. Results. Fifty-one asymptomatic and 53 symptomatic participantscompleted the study. For all visits, themeannoninvasive tear breakup timewas about 1 second longer withDT1 than withC1DandAVTE (p < 0.01).Overall, thewettability of all three lenses was good; however, DT1 was graded marginally better than the other lenses (both p < 0.01). On day 3, eyes wearing AVTE had significantly more dehydration-induced corneal staining compared with DT1 (AVTE, 24%; DT1, 11%; p < 0.01). After 8 hours, conjunctival staining was different between lenses (greatest with C1D and least with DT1; all p < 0.01). Conjunctival indentation was more prevalent with the C1D lenses (n = 70) compared with DT1 (n = 1; p < 0.01) and AVTE (n = 11; p < 0.01). Therewere no differences between asymptomatic and symptomatic lenswearers for any of the clinical parameters (all p 9 0.05). Conclusions. Each of the three SiHy DDCLs performed well. Noninvasive tear breakup time was longest and wettability was greater with DT1. C1D had the most conjunctival staining conjunctival indentation. There was no difference between asymptomatic and symptomatic wearers with regard to ocular response and contact lensYrelated parameters. These results suggest that SiHy DDCLs may be an excellent contact lens modality for the symptomatic patient.

Verma,M. S., Chen,P. Z., Jones,L., Gu,F. X. Controlling "chemical nose" biosensor characteristics by modulating gold nanoparticle shape and concentration Sensing and Bio-Sensing Research 2015;513-18 [ Show Abstract ]

Conventional lock-and-key biosensors often only detect a single pathogen because they incorporate biomolecules with high specificity. "Chemical nose" biosensors are overcoming this limitation and identifying multiple pathogens simultaneously by obtaining a unique set of responses for each pathogen of interest, but the number of pathogens that can be distinguished is limited by the number of responses obtained. Herein, we use a gold nanoparticle-based "chemical nose" to show that changing the shapes of nanoparticles can increase the number of responses available for analysis and expand the types of bacteria that can be identified. Using four shapes of nanoparticles (nanospheres, nanostars, nanocubes, and nanorods), we demonstrate that each shape provides a unique set of responses in the presence of different bacteria, which can be exploited for enhanced specificity of the biosensor. Additionally, the concentration of nanoparticles controls the detection limit of the biosensor, where a lower concentration provides better detection limit. Thus, here we lay a foundation for designing "chemical nose" biosensors and controlling their characteristics using gold nanoparticle morphology and concentration. © 2015 The Authors.

Verma,M. S., Rogowski,J. L., Jones,L., Gu,F. X. Colorimetric biosensing of pathogens using gold nanoparticles Biotechnology Advances 2015;33(6):666-680 [ Show Abstract ]

Rapid detection of pathogens is crucial to minimize adverse health impacts of nosocomial, foodborne, and waterborne diseases. Gold nanoparticles are extremely successful at detecting pathogens due to their ability to provide a simple and rapid color change when their environment is altered. Here, we review general strategies of implementing gold nanoparticles in colorimetric biosensors. First, we highlight how gold nanoparticles have improved conventional genomic analysis methods by lowering detection limits while reducing assay times. Then, we focus on emerging point-of-care technologies that aim at pathogen detection using simpler assays. These advances will facilitate the implementation of gold nanoparticle-based biosensors in diverse environments throughout the world and help prevent the spread of infectious diseases. © 2015 Elsevier Inc.

Woods,J., Woods,C., Fonn,D. Visual performance of a multifocal contact lens versus monovision in established presbyopes Optometry and Vision Science 2015;92(2):175-82 [ Show Abstract ]

PURPOSE: To compare subjective and objective visual performance of the Air Optix Aqua Multifocal lens to monovision in a group of subjects requiring a medium level of reading-addition power.

METHODS: Fifty participants with reading additions between 1.25 and 2.00 diopters (inclusive) were randomized into a prospective, crossover clinical trial. They wore monovision and multifocals for 2 weeks in a randomized order. High- and low-contrast logMAR (logarithm of the minimum angle of resolution) acuity and stereopsis were measured at the beginning and end of each period. During each phase, participants performed specific tasks followed by subjective rating surveys and also completed satisfaction rating surveys on days 3, 7, and 12; all were transferred in real time using BlackBerry smartphones. A general rating survey was completed at the dispensing and 2-week visits.

RESULTS: Forty-nine participants completed the study (mean age, 52 years). Distance and near high- and low-contrast acuities were significantly better (p < 0.05) with monovision at all visits. High-contrast intermediate acuity was only better (p < 0.05) with multifocals after 2 weeks. Stereopsis was equivalent after 2 weeks, but better (p < 0.05) with multifocals at dispensing. Subjective ratings were generally equivalent between modalities although there was a trend for multifocals to be rated higher for focus changing and driving, whereas monovision tended to be rated higher for near tasks. For both corrections, the satisfaction survey showed no significant change between days 3, 7, and 12, and the general survey showed that comfort was maintained but subjective vision ratings decreased significantly over the 2 weeks. Twenty-five participants (51%) preferred multifocals, 18 (37%) preferred monovision, and the remaining 6 (12%) declared both unacceptable.

CONCLUSIONS: In this cohort, distance and near acuities were better with monovision, whereas the subjective ratings tended to favor the Air Optix Aqua Multifocal, with the exception of near performance. Preference was statistically similar between both corrections, with a trend toward preferring the multifocal.

2014

Caffery,B. E., Joyce,E., Heynen,M. L., Ritter,R., Jones,L. A., Senchyna,M. Quantification of conjunctival TNF-a in aqueous-deficient dry eye Optometry and Vision Science 2014;91(2):156-162 [ Show Abstract ]

PURPOSE: This study aimed to quantify and compare conjunctival epithelial tumor necrosis factor (NF) a mRNA expression in Sjögren syndrome (SS), non-Sjögren syndrome aqueous-deficient dry eye (non-SS DE), and non-dry eye (NDE) control subjects. METHODS: A total of 76 subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 non-SS DE (confirmed by symptoms and Schirmer scores = 10 mm), and 26 NDE. Superior and temporal bulbar conjunctival epithelial cells were collected via impression cytology. Epithelial RNA was extracted, and TNF-a mRNA expression was quantified by real-time quantitative polymerase chain reaction. RESULTS: The expression of TNF-a mRNA was found to be significantly higher in the SS group (2.48 ± 1.79) compared to both non-SS DE (0.95 ± 1.18; p < 0.05) and NDE (0.84 ± 0.51; p < 0.05) groups. No difference in TNF-a mRNA expression was found between the non-SS DE and NDE groups (p = 0.67). CONCLUSIONS: These results demonstrate that SS-associated aqueous-deficient dry eye is associated with a significant upregulation of conjunctival epithelial TNF-a mRNA relative to both non-SS DE and control groups. The degree to which TNF-a mRNA is upregulated in SS may contribute to the severe ocular surface damage observed in these patients. Copyright © 2014 American Academy of Optometry.

Cheung,S., Lorentz,H., Drolle,E., Leonenko,Z., Jones,L. W. Comparative study of lens solutions' ability to remove tear constituents Optometry and Vision Science 2014;91(9):1045-1061 [ Show Abstract ]

PURPOSE: The purpose of this study was to use atomic force microscopy to compare and characterize the cleaning abilities of a hydrogen peroxide-based system (HPS) and a polyhexamethylene biguanide-containing multipurpose solution (MPS) at removing in vitro deposited tear film constituents, as well as to determine deposition patterns on various silicone hydrogel contact lenses. METHODS: Silicone hydrogel materials - balafilcon A (BA), lotrafilcon B (LB), and senofilcon A (SA) - were incubated for 1 week in an artificial tear solution (ATS) containing representative lipids, proteins, and salts from the tear film. Atomic force microscopy was used to resolve each lens before and after being cleaned overnight in HPS or MPS. Atomic force microscopy was used again to resolve HPS/MPS-cleaned lenses, which were reincubated in fresh ATS for 1 week, before and after an overnight clean in their respective cleaning solution. RESULTS: Atomic force microscopy imaging was able to characterize lens deposits with high resolution. Lenses incubated in ATS revealed distinct differences in their deposition pattern across lens materials. The surface of BA contained about 20-nm-high deposits, whereas deposit heights up to 150 nm completely occluded the surface of SA. Lotrafilcon B lenses revealed clusters of deposits up to 90 nm. The use of either lens solution left trace amounts of tear film constituents, although components from the MPS were seen adsorbed onto the surface after cleaning. Surface roughness (Ra) measurements revealed a significant difference between ATS-incubated and HPS/MPS-cleaned SA and LB lenses (p < 0.05). Ra between first incubated and HPS/MPS-cleaned reincubated SA and LB was also significant (p < 0.05). CONCLUSIONS: Unique variations in ATS deposition patterns were seen between lenses with atomic force microscopy. The application of both HPS and MPS removed most visible surface deposits. © American Academy of Optometry.

Gorbet,M., Peterson,R., McCanna,D., Woods,C., Jones,L., Fonn,D. Human corneal epithelial cell shedding and fluorescein staining in response to silicone hydrogel lenses and contact lens disinfecting solutions Current eye research 2014;39(3):245-256 [ Show Abstract ]

Purpose: A pilot study was conducted to evaluate human corneal epithelial cell shedding in response to wearing a silicone hydrogel contact lens/solution combination inducing corneal staining. The nature of ex vivo collected cells staining with fluorescein was also examined. Methods: A contralateral eye study was conducted in which up to eight participants were unilaterally exposed to a multipurpose contact lens solution/silicone hydrogel lens combination previously shown to induce corneal staining (renu® fresh™ and balafilcon A; test eye), with the other eye using a combination of balafilcon A soaked in a hydrogen peroxide care system (Clear Care®; control eye). Lenses were worn for 2, 4 or 6 hours. Corneal staining was graded after lens removal. The Ocular Surface Cell Collection Apparatus was used to collect cells from the cornea and the contact lens. Results: In the test eye, maximum solution-induced corneal staining (SICS) was observed after 2 hours of lens wear (reducing significantly by 4 hours; p < 0.001). There were significantly more cells collected from the test eye after 4 hours of lens wear when compared to the control eye and the collection from the test eye after 2 hours (for both; n = 5; p < 0.001). The total cell yield at 4 hours was 813 ± 333 and 455 ± 218 for the test and control eyes, respectively (N = 5, triplicate, p = 0.003). A number of cells were observed to have taken up the fluorescein dye from the initial fluorescein instillation. Confocal microscopy of fluorescein-stained cells revealed that fluorescein was present throughout the cell cytoplasm and was retained in the cells for many hours after recovery from the corneal surface. Conclusion: This pilot study indicates that increased epithelial cell shedding was associated with a lens-solution combination which induces SICS. Our data provides insight into the transient nature of the SICS reaction and the nature of fluorescein staining observed in SICS. © 2014 Informa Healthcare USA, Inc.

Hall,B. J., Jones,L. W., Dixon,B. Silicone allergies and the eye: Fact or fiction? Eye and Contact Lens 2014;40(1):51-57 [ Show Abstract ]

OBJECTIVE: The purpose of this manuscript was to review the evidence concerning the role of an allergic reaction to silicone as the basis for the reported increase in contact lens-associated infiltrates in wearers of silicone hydrogel contact lenses. METHODS: A literature review was undertaken to investigate the antigenic properties of silicone and the causes of contact lens-associated inflammatory reactions. RESULTS: Immune cells cannot interact with silicone directly but can interact with antigens on these lenses. These antigens could be due to tear film deposits, microbial contamination, or components of care systems used with these lenses. CONCLUSIONS: Inflammatory reactions associated with silicone hydrogel contact lens wear are not caused by an allergic reaction to silicone alone. © 2013 Contact Lens Association of Ophthalmologists.

Hall,B., McCanna,D., Jones,L. Identification of coagulase-negative staphylococci in daily disposable contact lens wearers Letters in applied microbiology 2014;59(3):313-319 [ Show Abstract ]

This study aimed to identify and quantify the number of contaminating organisms on daily disposable (DD) soft contact lenses, which may be responsible for mild cases of keratitis that occur with this lens wear modality. Ten participants wore DD lenses, and 10 participants wore planned replacement (PR) lenses. Lenses were collected aseptically and analysed for microbial contamination. Colony-forming units (CFU) were recorded, and representative colonies were used for identification using the API identification system. The DD lenses evaluated in this study were contaminated with coagulase-negative staphylococcus (CNS), ranging from 1 to 653 CFU. PR lenses showed more diversity in the types of contaminating micro-organisms and consisted of CNS, Gram-negative bacteria (Pseudomonas), a yeast (Candida) and a mould (Aspergillus), ranging from 1 to 230 CFU. CNS was the only type of micro-organism found on DD contact lenses and therefore may be the cause of any form of keratitis observed in DD lens wearers. © 2014 The Society for Applied Microbiology.

Hall,B., Phan,C. -M, Subbaraman,L., Jones,L. W., Forrest,J. Extraction versus in Situ techniques for measuring surface-adsorbed lysozyme Optometry and Vision Science 2014;91(9):1062-1070 [ Show Abstract ]

PURPOSE: To compare two techniques for measuring the activity of lysozyme deposited onto hydrogel contact lens and to image the binding of Micrococcus lysodeikticus to contact lenses. METHODS: Using a previously described protein extraction technique and a recently developed in situ technique, we measured the time-dependent activity of adsorbed lysozyme on six different contact lens materials during the first minute and up to 1 week of interaction with the material surface. Total activity of extracted lysozyme, total in situ activity, and the activity of the outer surface layer of sorbed lysozyme were determined using the two different techniques. Micrococcal cellular interaction with surface-adsorbed lysozyme was imaged using confocal microscopy. RESULTS: The differences between total extracted activities, total in situ activities, and surface activities were both measurable and material specific. In most cases, total extracted activity is greater than total in situ activity, which, in turn, is greater than surface activity. After 1 week, etafilcon A had the highest extracted activity at 137 µg/lens, followed by omafilcon A, balafilcon A, comfilcon A, senofilcon A, and lotrafilcon B at 27.4, 2.85, 2.02, 0.46, and 0.27 µg/lens, respectively. Micrococcal cell adhesion was greatest on contact lenses with high contact angles, such as balafilcon A, omafilcon A, and senofilcon A and lowest on contact lenses with low contact angles, such as etafilcon A, comfilcon A, and lotrafilcon B. Subsequent removal/prevention of adhered micrococcal cells was greatest on balafilcon A, which had the highest surface activity, and lowest on lotrafilcon B, which had the lowest surface activity. CONCLUSIONS: This study has measured and made direct comparisons between two established techniques for measuring the activity of adsorbed lysozyme. The extraction technique determines the activity of underlying layers of lysozyme or lysozyme within the matrix of the material. Conversely, the in situ technique allows conclusions to be drawn about only the biologically relevant lysozyme including the activity of just the outer surface of adsorbed lysozyme. © American Academy of Optometry.

Hui,A., Willcox,M., Jones,L. In vitro and in vivo evaluation of novel ciprofloxacin-releasing silicone hydrogel contact lenses Investigative Ophthalmology and Visual Science 2014;55(8):4896-4904 [ Show Abstract ]

PURPOSE. The purpose of this study was to evaluate ciprofloxacin-releasing silicone hydrogel contact lens materials in vitro and in vivo for the treatment of microbial keratitis. METHODS. Model silicone hydrogel contact lens materials were manufactured using a molecular imprinting technique to modify ciprofloxacin release kinetics. Various contact lens properties, including light transmission and surface wettability, were determined, and the in vitro ciprofloxacin release kinetics elucidated using fluorescence spectrophotometry. The materials then were evaluated for their ability to inhibit Pseudomonas aeruginosa growth in vitro and in an in vivo rabbit model of microbial keratitis. RESULTS. Synthesized lenses had similar material properties to commercial contact lens materials. There was a decrease in light transmission in the shorter wavelengths due to incorporation of the antibiotic, but over 80% light transmission between 400 and 700 nm. Modified materials released for more than 8 hours, significantly longer than unmodified controls (P 0.05), which is significantly less than corneas treated with unmodified control lenses or those that received no treatment at all (P < 0.05). CONCLUSIONS. These novel contact lenses designed for the extended release of ciprofloxacin may be beneficial to supplement or augment future treatments of sight-threatening microbial keratitis. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

Moezzi,A. M., Fonn,D., Varikooty,J., Simpson,T. L. Overnight corneal swelling with high and low powered silicone hydrogel lenses Journal of Optometry 2014;8(1):19-26 [ Show Abstract ]

Purpose: To compare central corneal swelling after eight hours of sleep in eyes wearing four different silicone hydrogel lenses with three different powers. Methods: Twenty-nine neophyte subjects wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60) and senofilcon A (Dk, 103) lenses in powers -3.00, -10.00 and +6.00 D on separate nights, in random order, and on one eye only. The contra-lateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. Results: For the +6.00 D and -10.00 D, lotrafilcon A induced the least swelling and galyfilcon A the most. The +6.00 D power, averaged across lens materials, induced significantly greater central swelling than the -10.00 and -3.00 D (Re-ANOVA, p < 0.001), (7.7 ± 2.9% vs. 6.8 ± 2.8% and 6.5 ± 2.5% respectively) but there was no difference between -10.00 and -3.00 D. Averaged for power, lotrafilcon A induced the least (6.2 ± 2.8%) and galyfilcon A the most (7.6 ± 3.0%) swelling at the center (Re-ANOVA, p < 0.001). Central corneal swelling with +6.00 D was significantly greater than -10.00 D lens power despite similar levels of average lens transmissibility of these two lens powers. Conclusions: The differences in corneal swelling of the lens wearing eyes are consistent with the differences in oxygen transmission of the silicone hydrogel lenses. In silicone hydrogel lenses central corneal swelling is mainly driven by central lens oxygen transmissibility. © 2013 Spanish General Council of Optometry.

Mohammadi,S., Jones,L., Gorbet,M. Extended latanoprost release from commercial contact lenses: In vitro studies using corneal models PLOS ONE 2014;9(9):e106653 [ Show Abstract ]

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6  of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitrocorneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

Ngo,W., Srinivasan,S., Schulze,M., Jones,L. Repeatability of grading meibomian gland dropout using two infrared systems Optometry and Vision Science 2014;91(6):658-667 [ Show Abstract ]

PURPOSE: To determine the interobserver and intraobserver repeatability in using the OCULUS Keratograph 4 (K4) and 5M (K5M) to grade meibomian gland (MG) dropout using meibography grading scales. METHODS: The inferior and superior eyelids of 40 participants (35 women, 5 men; mean age = 32 years) were imaged three times each on both instruments. The images were split into one training and two study sets; the latter were graded (four-point meibography scale) by two observers on two separate occasions (24 hours apart) to determine repeatability. Semiobjective quantification of percentage MG dropout was conducted using ImageJ on K4 and K5M images. A finer seven-point meibography scale was used to grade a separate set of K5M images. RESULTS: For the four-point scale, interobserver mean difference (MD) (±SD) was 0.08 (±0.55) on day 1 and 0.13 (±0.50) on day 2, and the concordance correlation coefficient (CCC) was 0.79 and 0.81 on days 1 and 2, respectively. Intraobserver MD (±SD) was 0.04 (±0.54), CCC = 0.79 for observer 1; intraobserver MD (±SD) was -0.09 (±0.60), CCC = 0.74 for observer 2. For the seven-point scale, interobserver MD (±SD) was 0.05 (±0.45), CCC = 0.89 on day 1, and interobserver MD (±SD) was 0.01 (±0.41), CCC = 0.91 on day 2. Intraobserver MD (±SD) was -0.10 (±0.35), CCC = 0.93 for observer 1, and intraobserver MD (±SD) was -0.06 (±0.30), CCC = 0.95 for observer 2. Percentage dropout measured between the K4 and K5M images showed lack of agreement, with 21.8% coefficient of repeatability. There was no significant correlation (r 0.05) between meibography score and clinical signs (corneal staining, gland expressibility, telangiectasia, vascularity, lash loss); however, there was a high correlation (r = 0.77; p < 0.05) between meibography score with percentage dropout. CONCLUSIONS: Observers graded from -1 to +1 grade units between and within themselves for a four-point scale, 95% of the time. Although the interobserver and intraobserver repeatability of the K4 and K5M were very similar, a high rate of disagreement in percentage dropout between K4 and K5M images suggests that the two instruments cannot be interchanged. Meibomian gland dropout scores did not correlate significantly with clinical signs. Using a finer scale may be beneficial for detecting change.

Phan,C. -M, Subbaraman,L. N., Jones,L. In vitro drug release of natamycin from ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin-functionalized contact lens materials Journal of Biomaterials Science, Polymer Edition 2014;25(17):1907-1919 [ Show Abstract ]

Purpose: The antifungal agent natamycin can effectively form inclusion complexes with beta-cyclodextrin (ß-CD) and 2-hydroxypropyl-ß-cyclodextrin (HP-ßCD) to improve the water solubility of natamycin by 16-fold and 152-fold, respectively (Koontz, J. Agric. Food. Chem. 2003). The purpose of this study was to develop contact lens materials functionalized with methacrylated ß-CD (MßCD) and methacrylated HP-ßCD (MHP-ßCD), and to evaluate their ability to deliver natamycin in vitro. Methods: Model conventional hydrogel (CH) materials were synthesized by adding varying amounts of MßCD and MHP-ßCD (0, 0.22, 0.44, 0.65, 0.87, 1.08% of total monomer weight) to a monomer solution containing 2-hydroxyethyl methacrylate (HEMA). Model silicone hydrogel (SH) materials were synthesized by adding similar concentrations of MßCD and MHP-ßCD to N,N-dimethylacrylamide (DMAA)/10% 3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS). The gels were cured with UV light, washed with ethanol and then, hydrated for 24 h (h). The model materials were then incubated with 2 mL of 100 g/mL of natamycin in phosphate buffered saline (PBS) pH 7.4 for 48 h at room temperature. The release of natamycin from these materials in 2 mL of PBS, pH 7.4 at 32 ± 2 °C was monitored using UV-vis spectrophotometry at 304 nm over 24 h. Results: For both CH and SH materials, functionalization with MßCD and MHP-ßCD improved the total amount of drugs released up to a threshold loading concentration, after which further addition of methacrylated CDs decreased the amount of drugs released (p < 0.05). The addition of CDs did not extend the drug release duration; the release of natamycin by all model materials reached a plateau after 12 h (p < 0.05). Overall, DMAA/10% TRIS materials released significantly more drug than HEMA materials (p < 0.05). The addition of MHP-ßCD had a higher improvement in drug release than MßCD for both HEMA and DMAA/10% TRIS gels (p < 0.05). Conclusions: A high loading concentration of methacrylated CDs decreases overall drug delivery efficiency, which likely results from an unfavorable arrangement of the CDs within the polymer network leading to reduced binding of natamycin to the CDs. HEMA and DMAA/10% TRIS materials functionalized with MHP-ßCD are more effective than those functionalized with MßCD to deliver natamycin.

Phan,C. -M, Subbaraman,L., Jones,L. Contact lenses for antifungal ocular drug delivery: A review Expert Opinion on Drug Delivery 2014;11(4):537-546 [ Show Abstract ]

Introduction: Fungal keratitis, a potentially blinding disease, has been difficult to treat due to the limited number of approved antifungal drugs and the taxing dosing regimen. Thus, the development of a contact lens (CL) as an antifungal drug delivery platform has the potential to improve the treatment of fungal keratitis. A CL can serve as a drug reservoir to continuously release drugs to the cornea, while limiting drug loss through tears, blinking, drainage and non-specific absorption. Areas covered: This review will provide a summary of currently available methods for delivering antifungal drugs from commercial and model CLs, including vitamin E coating, impregnated drug films, cyclodextrin-functionalized hydrogels, polyelectrolyte hydrogels and molecular imprinting. This review will also highlight some of the main factors that influence antifungal drug delivery with CLs. Expert opinion: Several novel CL materials have been developed, capable of extended drug release profiles with a wide range of antifungal drugs lasting from 8 h to as long as 21 days. However, there are factors, such as first-order release kinetics, effectiveness of continuous drug release, microbial resistance, ocular toxicity and potential complications from inserting a CL in an infected eye, that still need to be addressed before commercial applications can be realized. © Informa UK, Ltd.

Phan,C. -M, Subbaraman,L., Liu,S., Gu,F., Jones,L. In vitro uptake and release of natamycin Dex -b- PLA nanoparticles from model contact lens materials Journal of Biomaterials Science, Polymer Edition 2014;25(1):18-31 [ Show Abstract ]

Purpose: To evaluate the uptake and release of the antifungal agent natamycin encapsulated within poly(D,L-lactide)-dextran nanoparticles (Dex-b-PLA NPs) from model contact lens (CL) materials. Methods: Six model CL materials (gel 1:poly(hydroxyethyl methacrylate, pHEMA); gel 2:85% pHEMA: 15% [Tris(trimethylsiloxy)silyl]-propyl methacrylate (TRIS); gel 3: 75% pHEMA: 25% TRIS; gel 4: 85% N,N dimethylacrylamide (DMAA): 15% TRIS; gel 5:75% DMAA: 25% TRIS; and gel 6: DMAA) were prepared using a photoinitiation procedure. The gels were incubated in: (1) natamycin dissolved in deionized (DI) water and (2) natamycin encapsulated within Dex-b-PLA NPs in dimethylsulfoxide/DI water. Natamycin release from these materials was monitored using UV-visible spectrophotometry at 304 nm over 7 d. Results: Natamycin uptake by all model CL materials increased between 1 and 7 d (p < 0.001). The uptake of natamycin-NPs was higher than the uptake of the drug alone in DI water (p < 0.05). Drug release was higher in materials containing DMAA than pHEMA (p < 0.05). All gels loaded with natamycin-NPs also released more drug compared to gels soaked with natamycin in DI water (p < 0.001). After 1 h, CL materials loaded with natamycin alone released 28-82% of the total drug release. With the exception of gel 6, this burst released was reduced to 21-54% for CL materials loaded with natamycin-NPs. Conclusions: Model CL materials loaded with natamycin-Dex-b-PLA NPs were able to release natamycin for up to 12 h under infinite sink conditions. DMAA-TRIS materials may be more suitable for drug delivery of natamycin due to the higher drug release observed with these materials. © 2013 Taylor & Francis.

Phan,CM, Hui,A., Subbaraman,L., Jones,L. Insights to Using Contact Lenses for Drug Delivery Clin Exp Pharmacol 2014;3(145):2161-1459 [ Show Abstract ]

There has been considerable interest in the potential application of contact lenses for ocular drug delivery. This short communication provides an overview of the challenges faced by delivering drugs using contact lenses, highlights the solutions to limitations that have already been achieved, and describes the barriers that remain before commercial application can be realized.

Samsom,M., Chan,A., Iwabuchi,Y., Subbaraman,L., Jones,L., Schmidt,TA In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4) Tribology International 2014;89:27-33

Verma,M. S., Chen,P. Z., Jones,L., Gu,F. X. Branching and size of CTAB-coated gold nanostars control the colorimetric detection of bacteria RSC Advances 2014;4(21):10660-10668 [ Show Abstract ]

Rapid detection of pathogenic bacteria is challenging because conventional methods require long incubation times. Nanoparticles have the potential to detect pathogens before they can cause an infection. Gold nanostars have recently been used for colorimetric biosensors but they typically require surface modification with antibodies or aptamers for cellular detection. Here, CTAB-coated gold nanostars have been used to rapidly (<5 min) detect infective doses of a model Gram-positive pathogen Staphylococcus aureus by an instrument-free colorimetric method. Varying the amounts of gold nanoseed precursor and surfactant can tune the size and degree of branching of gold nanostars as studied here by transmission electron microscopy. The size and morphology of gold nanostars determine the degree and rate of color change in the presence of S. aureus. The optimal formulation achieved maximum color contrast in the presence of S. aureus and produced a selective response in comparison to polystyrene microparticles and liposomes. These gold nanostars were characterized using UV-Visible spectroscopy to monitor changes in their surface plasmon resonance peaks. The visual color change was also quantified over time by measuring the RGB components of the pixels in the digital images of gold nanostar solutions. CTAB-coated gold nanostars serve as a promising material for simple and rapid detection of pathogens. © 2014 The Royal Society of Chemistry.

Verma,M. S., Chen,P. Z., Jones,L., Gu,F. X. "Chemical nose" for the visual identification of emerging ocular pathogens using gold nanostars Biosensors and Bioelectronics 2014;61:386-390 [ Show Abstract ]

Ocular pathogens can cause serious damages in the eye leading to severe vision loss and even blindness if left untreated. Identification of pathogens is crucial for administering the appropriate antibiotics in order to gain effective control over ocular infection. Herein, we report a gold nanostar based "chemical nose" for visually identifying ocular pathogens. Using a spectrophotometer and nanostars of different sizes and degrees of branching, we show that the "chemical nose" is capable of identifying the following clinically relevant ocular pathogens with an accuracy of 99%: S. aureus, A. xylosoxidans, D. acidovorans and S. maltophilia. The differential colorimetric response is due to electrostatic aggregation of cationic gold nanostars around bacteria without the use of biomolecule ligands such as aptamers or antibodies. Transmission electron microscopy confirms that the number of gold nanostars aggregated around each bacterium correlates closely with the colorimetric response. Thus, gold nanostars serve as a promising platform for rapid visual identification of ocular pathogens with application in point-of-care diagnostics. © 2014 Elsevier B.V.

2013

Craig,J. P., Willcox,M. D. P., Argüeso,P., Maissa,C., Stahl,U., Tomlinson,A., Wang,J., Yokoi,N., Stapleton,F. The TFOS International Workshop on Contact Lens Discomfort: Report of the contact lens interactions with the tear film subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS123-TFOS156

Duench,S., Sorbara,L., Keir,N., Simpson,T., Jones,L. Impact of silicone hydrogel lenses and solutions on corneal epithelial permeability Optometry and Vision Science 2013;90(6):546-556 [ Show Abstract ]

PURPOSE: The primary purpose of this pilot study was to compare epithelial barrier function (EBF) and staining in a small group of participants using a silicone hydrogel (SH) lens worn on a daily basis with two different care regimens. Secondarily, the aim was to see if there was any correlation between corneal staining and EBF. METHODS: The corneal EBF of 10 non-lens wearers (control) and 15 age-matched asymptomatic SH contact lens wearers (test) were assessed using fluorophotometry. Biomicroscopy was performed to assess corneal staining after the EBF was measured. The lens wearers wore PureVision (FDA group V) SH lenses for two consecutive 1-month periods while using either Alcon Opti-Free Express or Renu Fresh using a randomized, investigator-masked, crossover design. Control subjects were assessed on one occasion, and lens wearers were examined before fitting with lenses and after 7, 14, and 28 days of lens wear, with each combination. RESULTS: Compared with the control group, both study groups had an increase in epithelial permeability at baseline (p = 0.04). There were no changes in EBF during the treatment period for either solution (p = 0.87). A significant difference in EBF was found between the test groups during the treatment period (p = 0.02), with greater permeability in the Renu Fresh-disinfected lenses. There was poor correlation between corneal staining and EBF (r = 0.35, p > 0.05) because of large individual variations. CONCLUSIONS: Daily wear of highly oxygen-permeable SH lenses increases corneal epithelial permeability to fluorescein probably because of increased mechanical effects. In addition, certain lens-solution interactions can add to this effect, as seen in this study. Despite having a low amount of central corneal staining in the Renu Fresh group, staining and EBF did not prove to be well correlated. The presence of central corneal staining is a confounding factor when measuring EBF. Copyright © 2013 American Academy of Optometry.

Dumbleton,K. A., Richter,D., Woods,C. A., Aakre,B. M., Plowright,A., Morgan,P. B., Jones,L. W. A multi-country assessment of compliance with daily disposable contact lens wear Contact Lens and Anterior Eye 2013;36(6):304-312 [ Show Abstract ]

Purpose: To investigate compliance with daily disposable contact lens (DDCL) wear and investigate re-use of lenses according to country and DDCL material worn. Methods: Optometrists invited eligible DDCL patients from their practices to participate in a survey on DDCL wear in Australia, Norway, the United Kingdom (UK) and the United States (US). Eligible participants completed an online or paper version of the survey. Results: 805 participants completed the survey (96% online): Australia 13%, Norway 32%, UK 17%, US 38%. The median age was 38 years; 66% were female. Silicone hydrogel (SiHy) DDCLs were worn by 14%. Overall, 9% were non-compliant with DDCL replacement; Australia 18%, US 12%, UK 7% and Norway 4%. There were no differences with respect to sex, years of contact lens wear experience or DDCL material (SiHy versus hydrogels). The primary reason for re-use was "to save money" (60%). Re-use of DDCLs resulted in inferior comfort at insertion and prior to lens removal (p= 0.001). 75% reported occasional napping and 28% reported sleeping overnight for at least one night in the preceding month, while wearing their DDCLs. Conclusion: Non-compliance with replacement of DDCLs occurred in all countries investigated; the rate was highest in Australia and lowest in Norway. Re-use of DDCLs was associated with reduced comfort. DDCL wearers often reported wearing lenses overnight. It is important for optometrists to counsel their patients on the importance of appropriate lens wear and replacement for DDCLs. © 2013 British Contact Lens Association.

Dumbleton,K. A., Spafford,M. M., Sivak,A., Jones,L. W. Exploring compliance: A mixed-methods study of contact lens wearer perspectives Optometry and Vision Science 2013;90(8):898-908 [ Show Abstract ]

PURPOSE: Using both quantitative and qualitative research methods, this article explores in detail the lens wear and care habits of adapted contact lens wearers and seeks a better understanding of what enables and constrains patient compliance with appropriate lens wear and lens care. METHODS: The study was conducted in two phases: a preliminary online questionnaire (quantitative phase), identifying types of noncompliance, and a series of sequentially conducted focus groups (qualitative phase), exploring constraints to, and enablers of, compliance. RESULTS: One hundred participants completed the online questionnaire; 12 of them also participated in one of four focus groups. The most frequently reported aspects of noncompliance revealed were failure to replace lenses when scheduled, inappropriate lens purchase and supply, sleeping while wearing lenses, use of tap water with lenses and failure to wash hands, failure to clean and replace cases regularly, and inappropriate use of care systems. Using an iterative process, a number of "themes" associated with noncompliance were identified in the focus group discussions. The most frequently occurring themes related to the consequences that may occur if patients were noncompliant with one or more aspects of their contact lens wear and the importance of receiving instructions regarding the most appropriate way to wear and care for their lenses. Most of the themes that emerged during the analysis were both constraints to, and enablers of, compliance. CONCLUSIONS: This study confirms the frequent types of noncompliance with contact lens wear and care while offering a greater understanding of what may constrain and enables contact lens wear and care compliance. Future qualitative studies may help eye care practitioners and the contact lens industry to develop strategies and tools to aid compliance and success in contact lens wear. © 2013 American Academy of Optometry.

Dumbleton,K., Caffery,B., Dogru,M., Hickson-Curran,S., Kern,J., Kojima,T., Morgan,P. B., Purslow,C., Robertson,D. M., Nelson,J. D. The TFOS International Workshop on Contact Lens Discomfort: Report of the subcommittee on epidemiology Investigative Ophthalmology and Visual Science 2013;54(11):TFOS20-TFOS36

Dumbleton,K., Richter,D., Bergenske,P., Jones,L. W. Compliance with lens replacement and the interval between eye examinations Optometry and Vision Science 2013;90(4):351-358 [ Show Abstract ]

PURPOSE: Eye care practitioners (ECPs) acknowledge that their patients do not always follow recommendations for lens replacement, but many may not realize the possible implications for their offices. The study was conducted to investigate whether there is a relationship between contact lens compliance and the interval between full eye examinations (IEE). METHODS: The study was conducted in ECP offices in the United States. Eye care practitioners and patients independently completed linked questionnaires, evaluating their contact lens wear and care. Patients were required to be current wearers of daily disposable (DD) lenses or reusable silicone hydrogel lenses with a manufacturer-recommended replacement frequency (MRRF) of 2 weeks (2WR) or 1 month (1MR). RESULTS: A total of 2147 questionnaires from 141 offices were eligible. Fifty-four percent of patients were wearing 2WR, 37% 1MR, and 9% DD lenses. Wearers of 2WR lenses were significantly less compliant with replacement than wearers of both DD and 1MR lenses (34% vs. 74% and 67%, both p < 0.001); patients purchasing an annual supply were more compliant (55% vs. 45%, p < 0.001). The mean IEE was 16 months and was longer for wearers who were noncompliant with the MRRF (17.4 months vs. 14.5 months, p < 0.001). Other factors affecting IEE were household income (p = 0.030), insurance (p < 0.001), purchase source (p < 0.001), and sex (p = 0.007). CONCLUSIONS: Patients who were not compliant with the MRRF had longer IEEs and were less likely to purchase an annual supply of lenses. Patients who purchased lenses from their ECP, had a higher household income, had eye examination insurance, and were female had shorter IEEs. Patients failing to replace their lenses when scheduled were also found to be less compliant with lens care procedures. Eye care practitioners should reinforce the importance of all aspects of lens wear and care with their patients, with the overall aim of reducing possible complications and retaining successful contact lens wearers in their offices. Copyright © 2013 American Academy of Optometry.

Dumbleton,K., Woods,C. A., Jones,L. W., Fonn,D. The impact of contemporary contact lenses on contact lens discontinuation Eye and Contact Lens 2013;39(1):93-99 [ Show Abstract ]

OBJECTIVES: Discontinuation or "dropout" from contact lens (CL) wear continues to afflict the CL industry. This study was conducted to determine whether the advent of new CL materials and designs has impacted the dropout rate and the reasons for discontinuation. METHODS: Current and lapsed CL wearers residing in Canada were recruited using Facebook to take part in an on line survey investigating CL wearing experiences during 2008 to 2010 and to establish the percentage of participants who temporarily and permanently discontinued CL wear during the period surveyed. RESULTS: Four thousand two hundred seven eligible surveys were received (64% female; median age 27 years). Forty percent had lapsed from lens wear for at least 4 months; however, 62% of the lapsed wearers (LWs) resumed wear. There were no differences between LWs and nonlapsed wearers (NLWs) with respect to gender; however, LWs were older, started lens wear when older, and had not worn lenses for as long as NLWs (all P<0.001). More NLWs than LWs wore silicone hydrogel CLs (49% vs. 38%, P<0.001) and more LWs than NLWs wore daily disposable lenses and hydrogel CLs (24% vs. 19% and 22% vs. 18%, respectively, P=0.001). Primary reasons for discontinuation were discomfort (24%), dryness (20%), red eyes (7%), and expense (7%). Compliance with lens replacement was no different between LWs and NLWs (48% vs. 45%). CONCLUSIONS: About 23% of those surveyed had discontinued CL wear permanently. The primary reasons for dropping out continue to be discomfort and dryness. Dropout rates were lower in silicone hydrogel wearers. © 2013 Lippincott Williams & Wilkins.

Efron,N., Brennan,N. A., Bright,F. V., Glasgow,B. J., Jones,L. W., Sullivan,D. A., Tomlinson,A., Zhang,J. Contact lens care and ocular surface homeostasis Contact Lens and Anterior Eye 2013;36(SUPPL.):S9-S13 [ Show Abstract ]

The early focus of contact lens wear and ocular health was on oxygen delivery. However, as we learn more about how the eye works, and investigate how the contact lens interacts with the cornea, the role of the tear film has risen in prominence. A healthy tear film is critical for normal ocular homeostasis, and abnormalities of the tear film are the primary cause of dry eye. In order to improve patient eye health and comfort during lens wear, we need to further elucidate the relationship among contact lenses, contact lens solutions, the tear film, and the corneal epithelium, and find ways to maintain homeostasis of the ocular surface. In this section, we review the latest data and opinions on this complex relationship between contact lenses and lens care solutions. © 2013 British Contact Lens Association.

Efron,N., Jones,L., Bron,A. J., Knop,E., Arita,R., Barabino,S., McDermott,A. M., Villani,E., Willcox,M. D. P., Markoulli,M. The TFOS International Workshop on Contact Lens Discomfort: Report of the contact lens interactions with the ocular surface and adnexa subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS98-TFOS122

Hall,B., Jones,L., Forrest,J. A. Measuring the kinetics and activity of adsorbed proteins: In vitro lysozyme deposited onto hydrogel contact lenses over short time periods Journal of Biomedical Materials Research - Part A 2013;101 A(3):755-764 [ Show Abstract ]

A new process has been developed to determine the biological activity of an intact layer of lysozyme deposited onto a biomaterial surface. This process is applied to a number of common hydrogel contact lenses. The activity of the surface-adsorbed protein is measured using a standard micrococcal activity assay, with extra steps to distinguish between protein on the surface and protein in solution. This is in contrast to protein extraction work in which the activity of all adsorbed protein is measured. For ionic materials, which are known to deposit large amounts of protein, particularly positively charged proteins such as lysozyme, there is evidence for loosely bound protein re-entering the solution, thus making it impossible to truly separate out the surface-adsorbed protein. This optimized process provides the first quantification of the biological activity of an intact layer of surface-adsorbed protein at a hydrogel interface. © 2012 Wiley Periodicals, Inc.

Jones,L., Brennan,N. A., González-Méijome,J., Lally,J., Maldonado-Codina,C., Schmidt,T. A., Subbaraman,L., Young,G., Nichols,J. J. The TFOS International Workshop on Contact Lens Discomfort: Report of the contact lens materials, design, and care subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS37-TFOS70

Jones,L., Powell,C. H. Uptake and release phenomena in contact lens care by silicone hydrogel lenses Eye and Contact Lens 2013;39(1):29-36 [ Show Abstract ]

Contact lens solutions are highly complex mixtures of biocides (preservatives), surfactants, and other agents designed to disinfect, clean, and wet contact lenses. The commercialization of silicone hydrogel (SiHy) lenses has resulted in unique challenges to the manufacturers of contact lens solutions, because the properties of these materials differ markedly from those seen previously with poly-hydroxyethyl methacrylate-based hydrogels. Historically, hydrogel lens uptake and release of low-molecular weight preservatives such as chlorhexidine and thimerosal were known to result in allergic reactions, resulting in corneal irritation, stinging, conjunctival hyperemia, development of corneal infiltrates, palpebral lid changes, and corneal staining. However, little is known about the interaction of modern care systems with modern soft lens materials. Factors to be considered when evaluating the uptake and release of care components include the water content, charge, relative hydrophobicity, surface treatment, and porosity of the lens material, in conjunction with the concentration, charge/molecule, ionicity in the product matrix, molecular weight, and hydrophobicity of the care component in question. These factors control the sorption of the solution components by lenses, resulting in a variety of differences in the amount of the component taken up into the lens material and the amount and rate of subsequent release onto the ocular surface. Because both natural (ocular) and environmental biota become part of the solution-lens system during regimen use of any lens care product, these extraneously introduced substances should also be considered regarding their potential for uptake and either subsequent release onto the ocular surface or functioning as a scaffold for the adhesion of microbes. This article will review current knowledge concerning these interactions and investigate what clinically observable complications may arise from these interactions. It also reviews whether current methods to determine these interactions could be improved on. © 2013 Lippincott Williams & Wilkins.

Keech,A., Senchyna,M., Jones,L. Impact of time between collection and collection method on human tear fluid osmolarity Current eye research 2013;38(4):428-436 [ Show Abstract ]

Aim: To generate data on the variability of tear osmolarity in a control (normal, non-dry eye) and symptomatic dry eye population (Ocular Surface Disease Index: OSDI ≥20). A secondary outcome is the determination of the effect that tear collection technique has on the osmolarity of the sample. Materials and methods: This was a two-phase study that recruited 20 subjects (n = 10 normal, n = 10 dry eye) to evaluate the influence of time between measurements (Phase I) and 30 subjects (n = 15 normal, n = 15 dry eye) to evaluate the influence of collection technique (Phase II). As part of Phase I, serial tear osmolarity measurements were performed on each eye; four separated by 15min followed by four separated by lmin, at each of three visits. Phase II compared the consecutive measurement of four in vivo tear samples to four in vitro measurements on tears collected and dispensed from a glass capillary tube. Results: During Phase I, the dry eye group had a significantly higher maximum osmolarity (334.2 ± 25.6 mOsm/L) compared to the normal group (304.0 ± 8.4mOsm/L, p = 0.002). No significant differences were observed whether collections were performed at 15 or 1 min intervals. During Phase II, the in vivo osmolarity was equivalent to in vitro measurements from glass capillary tube samples for both the dry eye group (323.0± 16.7mOsm/L versus 317.7±24.8, p = 0.496), and for the normal subjects (301.2±7. 2mOsm/L versus 301.9 ± 16.0 mOsm/L, p = 0.884). Conclusion: Symptomatic dry eye subjects exhibited a significantly higher tear osmolarity and variation over time than observed in normal subjects, reflecting the inherent tear film instability of dry eye disease. There was no change in the distribution of tear osmolarity measurements whether tears were collected in rapid succession or given time to equilibrate, and collection method had no impact on tear osmolarity. © Informa Healthcare USA Inc.

Keir,N., Jones,L. Wettability and silicone hydrogel lenses: A review Eye and Contact Lens 2013;39(1):100-108 [ Show Abstract ]

One of the major breakthroughs in the development of silicone hydrogel contact lenses has related to the ability of manufacturers to overcome the surface hydrophobicity that occurred with silicone elastomer lenses. However, the wettability of silicone hydrogel lenses continues to be of interest as a potential link between in vivo lens performance and contact lens-related comfort. This article will review some of the knowledge we have gained in the area of contact lens wettability over the past decade and will discuss some of the challenges related to its measurement. © 2013 Lippincott Williams & Wilkins.

Ng,A., Heynen,M., Luensmann,D., Subbaraman,L. N., Jones,L. Impact of tear film components on the conformational state of lysozyme deposited on contact lenses Journal of Biomedical Materials Research - Part B Applied Biomaterials 2013;101(7):1172-1181 [ Show Abstract ]

Purpose To investigate the impact of lactoferrin and lipids on the kinetic denaturation of lysozyme deposited on silicone and conventional hydrogel lenses, using a complex artificial tear solution (ATS). Methods Two silicone hydrogel lenses (AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A) and two conventional hydrogel lenses (ACUVUE 2; etafilcon A and PROCLEAR; omafilcon A) were incubated in four solutions: an ATS, ATS without lactoferrin, ATS without lipids, and ATS without lactoferrin and lipids. At various time points over a 28-day period, the percentage of active lysozyme per lens was determined using a fluorescence activity assay and an ELISA. Results After 28 days, the percentage of active lysozyme extracted from etafilcon A lenses in all solutions was significantly higher than all other lens materials (p 0.05). The inclusion of lipids in the ATS significantly increased the lysozyme denaturation on both silicone hydrogel materials (p 0.05). The inclusion of lipids in the ATS significantly increased the lysozyme denaturation on both silicone hydrogel materials (p 0.05). Conclusions Lactoferrin and lipids have an impact on the denaturation of lysozyme deposited onto silicone hydrogel contact lenses, while conventional hydrogel lenses were unaffected. Future in vitro studies should consider the impact of tear film components when investigating protein deposition and denaturation on contact lenses. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 1172-1181, 2013. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Ng,A., Heynen,M., Luensmann,D., Subbaraman,L. N., Jones,L. Optimization of a fluorescence-based lysozyme activity assay for contact lens studies Current eye research 2013;38(2):252-259 [ Show Abstract ]

Purpose: To optimize a fluorescence-based lysozyme activity assay to investigate the conformational state of lysozyme in solution and to determine the impact of extraction and evaporation procedures and the possible interference of contact lens materials on lysozyme activity. Methods: The fluorescence-based lysozyme activity assay, Enzchek (Molecular Probes Inc, Eugene, OR) which utilizes fluorescently quenched Micrococcus lysodeikticus, was compared to the gold standard, classical lysozyme turbidity assay, using four differently concentrated lysozyme samples (20, 10, 5.0 and 2.0 ng/µL). Furthermore, six differently concentrated lysozyme samples (2.0, 1.0, 0.5, 0.25, 0.125 and 0.01 µg/µL) were quantified using the fluorescence-based assay in the presence of extraction solvents consisting of 0.2% and 0.02% trifluroacetic acid/acetonitrile and following evaporation procedures. Results: A standard curve was generated by the fluorescence-based assay ranging from 2 to 150 ng. The total active lysozyme quantified in the four lysozyme samples was not significantly different between the two assays (p > 0.05) and the concordance correlation coefficient was determined to be 0.995. However an average discrepancy between the two assays was found to be 0.474 ng, with the turbidity assay typically reporting higher active lysozyme measurements. The sensitivity of the fluorescence-based assay was higher than the classical turbidity assay when quantifying 20 ng or less active lysozyme. Following the extraction and evaporation procedures and the addition of lens extracts, the total active lysozyme recovered was 95% or greater. Conclusions: In comparison to the classical turbidity assay, the fluorescence-based assay is a very sensitive method, making it a favorable technique, particularly when studying contact lens materials that deposit relatively low levels of lysozyme. © Informa Healthcare USA, Inc.

Ngo,W., Srinivasan,S., Jones,L. Historical overview of imaging the meibomian glands Journal of Optometry 2013;6(1):1-8 [ Show Abstract ]

Growing knowledge of the role of the meibomian glands in dry eye disease and contact lens discomfort has resulted in a surge of interest in visualizing these glands within the eyelids. This manuscript provides an overview of the many different visualization methods that have evolved over the past 30-40 years. Some of the visualization methods covered in this review include lid transillumination, video and non-contact meibography, and imaging methods employing confocal microscopy, optical coherence tomography and ultrasound. This review has also highlighted all the studies to date that have employed meibography as part of their methods. An overview of the available meibography dropout grading systems will also be provided. © 2012 Spanish General Council of Optometry.

Nichols,J. J., Jones,L., Daniel Nelson,J., Stapleton,F., Sullivan,D. A., Willcox,M. D. P. The TFOS International Workshop on Contact Lens Discomfort: Introduction Investigative Ophthalmology and Visual Science 2013;54(11):TFOS1-TFOS6

Nichols,J. J., Willcox,M. D. P., Bron,A. J., Belmonte,C., Ciolino,J. B., Craig,J. P., Dogru,M., Foulks,G. N., Jones,L., Nelson,J. D., Nichols,K. K., Purslow,C., Schaumberg,D. A., Stapleton,F., Sullivan,D. A. The TFOS International Workshop on Contact Lens Discomfort: Executive summary Investigative Ophthalmology and Visual Science 2013;54(11):TFOS7-TFOS13

Nichols,K. K., Redfern,R. L., Jacob,J. T., Nelson,J. D., Fonn,D., Forstot,S. L., Huang,J. -F, Holden,B. A., Nichols,J. J. The TFOS International Workshop on Contact Lens Discomfort: Report of the definition and classification subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS14-TFOS19

Papas,E. B., Ciolino,J. B., Jacobs,D., Miller,W. S., Pult,H., Sahin,A., Srinivasan,S., Tauber,J., Wolffsohn,J. S., Nelson,J. D. The TFOS International Workshop on Contact Lens Discomfort: Report of the management and therapy subcommittee Investigative Ophthalmology and Visual Science 2013;54(11):TFOS183-TFOS203

Phan,C. -M, Subbaraman,L. N., Jones,L. In vitro uptake and release of natamycin from conventional and silicone hydrogel contact lens materials Eye and Contact Lens 2013;39(2):162-168 [ Show Abstract ]

OBJECTIVES:: To investigate the uptake and release of the antifungal ocular drug, natamycin from commercially available conventional hydrogel (CH) and silicone hydrogel (SH) contact lens (CL) materials and to evaluate the effectiveness of this delivery method. METHODS:: Five commercial SH CLs (balafilcon A, comfilcon A, galyfilcon A, senofilcon A, and lotrafilcon B) and four CH CLs (etafilcon A, omafilcon A, polymacon, vifilcon A) were examined in this study. These lenses were incubated with natamycin solubilized in dimethyl sulfoxide, and the release of the drug from these lenses, in Unisol 4 pH 7.4 at 32±1 C, was determined using UV-visible spectrophotometry at 305 nm over 24 hours. RESULTS:: There was a significant uptake of natamycin between 0 hour and 24 hours (P0.05). There was a significant difference in release between all the SH materials (P0.05). There was a significant difference in release between all the SH materials (P0.05). There was a significant difference in release between all the SH materials (P0.05). Overall, the release of natamycin was higher in CH than SH lenses (P<0.001). CONCLUSIONS:: All CLs released clinically relevant concentrations of natamycin within 30 minutes, but this release reached a plateau after approximately 1 hour. Further CL material development will be necessary to produce a slow and sustained drug releasing device for the delivery of natamycin. © 2013 Lippincott Williams & Wilkins.

Robinson,B., Feng,Y., Woods,C. A., Fonn,D., Gold,D., Gordon,K. Prevalence of visual impairment and uncorrected refractive error-report from a canadian urban population-based study Ophthalmic epidemiology 2013;20(3):123-130 [ Show Abstract ]

Purpose: The prevalence of visual impairment due to uncorrected refractive error has not been previously studied in Canada. A population-based study was conducted in Brantford, Ontario. Methods: The target population included all people 40 years of age and older. Study participants were selected using a randomized sampling strategy based on postal codes. Presenting distance and near visual acuities were measured with habitual spectacle correction, if any, in place. Best corrected visual acuities were determined for all participants who had a presenting distance visual acuity of less than 20/25. Results: Population weighted prevalence of distance visual impairment (visual acuity <20/40 in the better eye) was 2.7% (n=768, 95% confidence interval (CI) 1.8-4.0%) with 71.8% correctable by refraction. Population weighted prevalence of near visual impairment (visual acuity <20/40 with both eyes) was 2.2% (95% CI 1.4-3.6) with 69.1% correctable by refraction. Multivariable adjusted analysis showed that the odds of having distance visual impairment was independently associated with increased age (odds ratio, OR, 3.56, 95% CI 1.22-10.35; 65 years compared to those 39-64 years), and time since last eye examination (OR 4.93, 95% CI 1.19-20.32; 5 years compared to 2 years). The same factors appear to be associated with increased prevalence of near visual impairment but were not statistically significant. Conclusions: The majority of visual impairment found in Brantford was due to uncorrected refractive error. Factors that increased the prevalence of visual impairment were the same for distance and near visual acuity measurements. © 2013 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.

Srinivasan,S., Heynen,M. L., Martell,E., Ritter III,R., Jones,L., Senchyna,M. Quantification of MUCIN 1, cell surface associated and MUCIN16, cell surface associated proteins in tears and conjunctival epithelial cells collected from postmenopausal women Molecular Vision 2013;19970-979 [ Show Abstract ]

Purpose: To quantify the expression of mucin 1, cell surface associated (MUC1) and mucin 16, cell surface associated (MUC16) proteins and messenger ribonucleic acid (mRNA) in a cohort of postmenopausal women (PMW), to explore the relationship between mucin expression, dry eye symptomology, and tear stability. Methods: Thirty-nine healthy PMW (>50 years of age) were enrolled in this study. No specific inclusion criteria were used to define dry eye; instead, a range of subjects were recruited based on responses to the Allergan Ocular Surface Disease Index (OSDI) questionnaire and tear stability measurements as assessed by non-invasive tear breakup time (NITBUT). Tears were collected from the inferior tear meniscus using a disposable glass capillary tube, and total RNA and total protein were isolated from conjunctival epithelial cells collected via impression cytology. Expression of membrane-bound and soluble MUC1 and MUC16 were quantified with western blotting, and expression of MUC1 and MUC16 mRNA was assessed with real-time PCR. Results: OSDI responses ranged from 0 to 60, and NITBUT ranged from 18.5 to 2.9 s. Only two statistically significant correlations were found: soluble MUC16 protein concentration and MUC16 mRNA expression with OSDI vision related (-0.47; p=0.01) and ocular symptom (0.39; p=0.02) subscores, respectively. Post hoc exploratory analysis on absolute expression values was performed on two subsets of subjects defined as asymptomatic (OSDI =6, n=12) and moderate to severe symptomatic (OSDI =20, n=12). The only significant difference between the two subgroups was a significant reduction in MUC16 mRNA expression found in the symptomatic dry eye group (1.52±1.19 versus 0.57±0.44; p=0.03). Conclusions: A broad exploration of mucin expression compared to either a sign (NITBUT) or symptoms of dry eye failed to reveal compelling evidence supporting a significant relationship, other than a potential association between MUC16 with specific symptoms. Furthermore, comparison of mucin protein and expression levels between the asymptomatic and moderate to severe symptomatic subgroups revealed only one significant difference, a reduction in MUC16 mRNA expression in the symptomatic subgroup. © 2013 Molecular Vision.

Srinivasan,S., Menzies,K. L., Sorbara,L., Jones,L. W. Imaging meibomian glands on a patient with chalazia in the upper and lower lids: A case report Contact Lens and Anterior Eye 2013;36(4):199-203 [ Show Abstract ]

Aim: To describe the meibomian gland (MG) appearance in a case of eyelid chalazia, using a novel meibography method. Methods: A 29-year-old female of South Asian origin presented with mild swelling in the lower lid of the left eye. The patient also presented with a history of a recurrent chalazion in the upper lid of the same eye, which later progressed to an active chalazion. A chalazion also developed in the upper lid of the right eye. Meibography was performed using a novel Keratograph (Keratograph 4, OCULUS, Wetzlar, Germany) to evaluate the structure of the MG in the area affected by the chalazia. Results: The area of the recurrent chalazion in the upper left lid showed partial and/or complete MG loss. The active chalazia in the lower left lid and the upper right lid showed inflammation and MG drop out at the affected site. The inflammation was found to be reduced during the follow-up visits, however disappearance of MG very specific to the region of the chalazion was observed. Conclusion: The Keratograph 4 was able to image the MG structures clearly, allowing the clinician to monitor the progression of chalazia and the MG loss in the affected areas. © 2013 British Contact Lens Association.

Varikooty,J., Keir,N., Richter,D., Jones,L. W., Woods,C., Fonn,D. Comfort response of three silicone hydrogel daily disposable contact lenses Optometry and Vision Science 2013;90(9):945-953 [ Show Abstract ]

PURPOSE: To evaluate subjective ocular comfort across the day with three silicone hydrogel daily disposables (SHDDs) in a group of adapted lens wearers. METHODS: Masked subjects (asymptomatic or symptomatic of end-of-day (EOD) dryness with habitual lenses) wore three SHDDs: DAILIES TOTAL1 (DT1), Clariti 1day (C1D), or 1-DAY ACUVUE TRUEYE (AVTE), each for 3 days. On day 2, wearing time (WT) and comfort ratings after insertion, at 4, 8, and 12 hours, and at EOD were recorded. Because not all subjects wore lenses for 12 hours, comfort was analyzed across the day (up to 8 hours, 8 to 12 hours), and a new variable ("cumulative comfort" [CC]) was calculated for EOD. RESULTS: One hundred four subjects completed the study (51 asymptomatic, 53 symptomatic). The two groups had different WTs (mean WT, 14.0 and 12.7 hours, respectively; p < 0.001). Ocular comfort was rated higher in the asymptomatic group throughout the day (p < 0.001). One hundred four subjects wore all three SHDDs for at least 8 hours, whereas 74 (45 asymptomatic, 29 symptomatic) subjects wore them for 12 hours or longer. Comfort ratings were higher with DT1 (least square means [LSM] = 91.0) than with C1D (LSM = 86.5; p < 0.001) and AVTE (LSM = 87.7; p = 0.011) for the first 8 hours and lower with C1D compared with DT1 (p = 0.012) from 8 to 12 hours. Mean EOD (± SD) comfort with the C1D lens was 72 ± 21, lower than both DT1 (mean, 79 ± 17; p = 0.001) and AVTE (mean, 78 ± 21; p = 0.010). Mean CC was higher in the asymptomatic group (mean, 1261 ± 59) compared with that in the symptomatic group (mean, 1009 ± 58; p < 0.001) and higher for DT1 (mean, 1184 ± 258) than C1D (mean, 1094 ± 318; p = 0.002) and AVTE (mean, 1122 ± 297; p = 0.046). CONCLUSIONS: All three SHDDs had average WTs of 12 hours or longer for 1 day. Comfort during the first 12 hours was highest with DT1 (similar to AVTE between 8 and 12 hours) and lowest with C1D. End-of-day comfort was lowest with C1D, and CC was highest for DT1. Cumulative comfort may be a valuable new metric to assess ocular comfort during the day. © 2013 American Academy of Optometry.

Walther,H., Lorentz,H., Heynen,M., Kay,L., Jones,L. W. Factors that influence in vitro cholesterol deposition on contact lenses Optometry and Vision Science 2013;90(10):1057-1065 [ Show Abstract ]

PURPOSE: The purpose of this study was to analyze the impact that incubation time, lipid concentration, and solution replenishment have on silicone hydrogel (SiHy) and conventional hydrogel (CH) contact lens cholesterol deposition via in vitro radiochemical experiments. METHODS: Four SiHy (senofilcon A, lotrafilcon B, comfilcon A, balafilcon A) and two CH (etafilcon A and omafilcon A) contact lenses were incubated in an artificial tear solution (ATS) that contained major tear film proteins, lipids, salts, salts, and a trace amount of radioactive C-cholesterol. Lenses were incubated for various incubation times (1, 3, 7, 14, or 28 days), with three concentrations of lipid (0.5×, 1×, 2× tear film concentration) and with or without solution replenishment to assess each variable's impact on cholesterol deposition. After incubation, the lenses were extracted using 2:1 chloroform:methanol, extracts were analyzed in a beta counter and masses (micrograms per lens) were extrapolated from standard curves. RESULTS: Within the SiHy materials, balafilcon A deposited the greatest amount of cholesterol (p replenishing > 1× > 0.5×. CONCLUSIONS: Overall, SiHy lenses deposit significantly more cholesterol than CH lens materials, and the mass of lipid deposited is dependent on the contact lens material, length of incubation, concentration of lipids in the ATS, and the replenishment of ATS. Copyright © 2013 American Academy of Optometry.

Weeks,A., Boone,A., Luensmann,D., Jones,L., Sheardown,H. The effects of hyaluronic acid incorporated as a wetting agent on lysozyme denaturation in model contact lens materials Journal of Biomaterials Applications 2013;28(3):323-333 [ Show Abstract ]

Conventional and silicone hydrogels as models for contact lenses were prepared to determine the effect of the presence of hyaluronic acid on lysozyme sorption and denaturation. Hyaluronic acid was loaded into poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) hydrogels, which served as models for conventional and silicone hydrogel contact lens materials. The hyaluronic acid was cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide in the presence of dendrimers. Active lysozyme was quantified using a Micrococcus lysodeikticus assay while total lysozyme was determined using 125-I radiolabeled protein. To examine the location of hyaluronic acid in the gels, 6-aminofluorescein labeled hyaluronic acid was incorporated into the gels using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry and the gels were examined using confocal laser scanning microscopy. Hyaluronic acid incorporation significantly reduced lysozyme sorption in poly(2-hydroxyethyl methacrylate) (p < 0.00001) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) (p < 0.001) hydrogels, with the modified materials sorbing only 20% and 16% that of the control, respectively. More importantly, hyaluronic acid also decreased lysozyme denaturation in poly(2-hydroxyethyl methacrylate) (p < 0.005) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) (p < 0.02) hydrogels. The confocal laser scanning microscopy results showed that the hyaluronic acid distribution was dependent on both the material type and the molecular weight of hyaluronic acid. This study demonstrates that hyaluronic acid incorporated as a wetting agent has the potential to reduce lysozyme sorption and denaturation in contact lens applications. The distribution of hyaluronic acid within hydrogels appears to affect denaturation, with more surface mobile, lower molecular weight hyaluronic acid being more effective in preventing denaturation. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Weeks,A., Subbaraman,L. N., Jones,L., Sheardown,H. Physical entrapment of hyaluronic acid during synthesis results in extended release from model hydrogel and silicone hydrogel contact lens materials Eye and Contact Lens 2013;39(2):179-185 [ Show Abstract ]

OBJECTIVES:: This study was designed to assess the duration of hyaluronic acid (HA) release from model contact lens materials when HA was physically incorporated into the hydrogel during synthesis and to assess the effects of the HA release on lysozyme sorption. METHODS:: Model conventional and silicone hydrogel contact lens materials containing HA of various molecular weights as a releasable wetting agent were prepared. The HA was released into phosphate-buffered saline and MilliQ water, and the release was monitored using ultraviolet spectroscopy. Hyaluronic acid release was quantified by enzyme-linked immunosorbent assay. The effect of the releasable HA on lysozyme sorption to the materials was also analyzed using 125-I-labeled protein. RESULTS:: Hyaluronic acid loaded into the materials using this method could be released from conventional hydrogel materials for 21 days; the model silicone hydrogels showed release of more than 7 weeks. With one exception, the releasable HA decreased lysozyme sorption. CONCLUSIONS:: Hyaluronic acid physically incorporated into contact lens materials during synthesis may therefore be released for extended periods of time of up to 7 weeks. Hyaluronic acid release leads to decreased protein adsorption in general. This method has potential for modification of conventional and silicone hydrogel lenses with releasable HA as a wetting agent. © 2013 Lippincott Williams & Wilkins.

Woods,J., Guthrie,S. E., Keir,N., Dillehay,S., Tyson,M., Griffin,R., Choh,V., Fonn,D., Jones,L., Irving,E. Inhibition of defocus-induced myopia in chickens Investigative Ophthalmology and Visual Science 2013;54(4):2662-2668 [ Show Abstract ]

PURPOSE. To determine the effect of wearing a lens with a unique peripheral optical design on the development and progression of defocus-induced myopia in newly hatched chickens.METHODS. Eighty-five newly hatched chickens underwent bilateral retinoscopy and A-scan ultrasound to determine their refractive error and axial length. They were randomly divided into Control and two Test groups, in which each chicken was fitted with a goggle-lens over the right eye, with the left eye remaining untreated. The Control group wore a lens of power - 10.00 diopters (D) of standard spherical optical design. The two Test lenses both had a central optical power -10.00 D, but used different peripheral myopia progression control (MPC) designs. For all groups, retinoscopy was repeated on days 3, 7, 10, and 14; ultrasound was repeated on day 14.RESULTS. On day 0 there was no statistical difference in refractive error (mean +6.92 D) or axial length (mean 8.06 mm) between Test and Control groups or treated and untreated eyes (all P > 0.05). At day 14, 37 (43.5%) of 85 chickens had not experienced goggle detachment and were included in the final analyses. In this cohort there was a significant refractive difference between the treated eyes of the Control group (n = 17) and those of Test 1 (n = 14) and Test 2 (n = 6) groups (both P < 0.01): Control -4.65 ± 2.11 D, Test 1 +4.57 ± 3.11 D, Test 2 +1.08 ± 1.24 D (mean ± SEM). There was also a significant axial length difference (both P < 0.01): Control 10.55 ± 0.36 mm, Test 1 9.99 ± 0.14 mm, Test 2 10.17 ± 0.18 mm.CONCLUSIONS. Use of these unique MPC lens designs over 14 days caused a significant reduction in the development of defocus-induced myopia in chickens; the degree of reduction appeared to be design specific. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

2012

Dumbleton,K., Woods,C. A., Jones,L. W., Fonn,D. The impact of contemporary contact lenses on contact lens discontinuation Eye and Contact Lens 2012 [ Show Abstract ]

OBJECTIVES: Discontinuation or "dropout" from contact lens (CL) wear continues to afflict the CL industry. This study was conducted to determine whether the advent of new CL materials and designs has impacted the dropout rate and the reasons for discontinuation. METHODS: Current and lapsed CL wearers residing in Canada were recruited using Facebook to take part in an on line survey investigating CL wearing experiences during 2008 to 2010 and to establish the percentage of participants who temporarily and permanently discontinued CL wear during the period surveyed. RESULTS: Four thousand two hundred seven eligible surveys were received (64% female; median age 27 years). Forty percent had lapsed from lens wear for at least 4 months; however, 62% of the lapsed wearers (LWs) resumed wear. There were no differences between LWs and nonlapsed wearers (NLWs) with respect to gender; however, LWs were older, started lens wear when older, and had not worn lenses for as long as NLWs (all P<0.001). More NLWs than LWs wore silicone hydrogel CLs (49% vs. 38%, P<0.001) and more LWs than NLWs wore daily disposable lenses and hydrogel CLs (24% vs. 19% and 22% vs. 18%, respectively, P≤0.001). Primary reasons for discontinuation were discomfort (24%), dryness (20%), red eyes (7%), and expense (7%). Compliance with lens replacement was no different between LWs and NLWs (48% vs. 45%). CONCLUSIONS: About 23% of those surveyed had discontinued CL wear permanently. The primary reasons for dropping out continue to be discomfort and dryness. Dropout rates were lower in silicone hydrogel wearers.

Hui,A., Sheardown,H., Jones,L. Acetic and acrylic acid molecular imprinted model silicone hydrogel materials for ciprofloxacin-HCL delivery 2012;5(1):85-107 [ Show Abstract ]

Contact lenses, as an alternative drug delivery vehicle for the eye compared to eye drops, are desirable due to potential advantages in dosing regimen, bioavailability and patient tolerance/compliance. The challenge has been to engineer and develop these materials to sustain drug delivery to the eye for a long period of time. In this study, model silicone hydrogel materials were created using a molecular imprinting strategy to deliver the antibiotic ciprofloxacin. Acetic and acrylic acid were used as the functional monomers, to interact with the ciprofloxacin template to efficiently create recognition cavities within the final polymerized material. Synthesized materials were loaded with 9.06 mM, 0.10 mM and 0.025 mM solutions of ciprofloxacin, and the release of ciprofloxacin into an artificial tear solution was monitored over time. The materials were shown to release for periods varying from 3 to 14 days, dependent on the loading solution, functional monomer concentration and functional monomer:template ratio, with materials with greater monomer:template ratio (8:1 and 16:1 imprinted) tending to release for longer periods of time. Materials with a lower monomer:template ratio (4:1 imprinted) tended to release comparatively greater amounts of ciprofloxacin into solution, but the release was somewhat shorter. The total amount of drug released from the imprinted materials was sufficient to reach levels relevant to inhibit the growth of common ocular isolates of bacteria. This work is one of the first to demonstrate the feasibility of molecular imprinting in model silicone hydrogel-type materials.

Jadi,S., Heynen,M., Luensmann,D., Jones,L. Composition of incubation solution impacts in vitro protein uptake to silicone hydrogel contact lenses Molecular Vision 2012;18337-347 [ Show Abstract ]

Purpose: To determine the impact of incubation solution composition on protein deposition to silicone hydrogel (SH) contact lenses using a simplistic and a complex model of the tear film. Methods: Three SH materials - senofilcon A (SA), lotrafilcon B (LB), and balafilcon A (BA) - were incubated in two different solutions; Solution A was a simplistic augmented buffered saline solution containing a single protein, whereas Solution B was a complex artificial tear solution (ATS), containing the augmented buffered saline solution in addition to proteins, lipids, and mucins (pH=7.4). The proteins of interest (lysozyme, lactoferrin, albumin) were radiolabeled with Iodine-125 (2% protein of interest) and the accumulation of the conjugated protein to the lens materials was determined after 1, 7, 14, and 28 days of incubation. Protein deposition was measured using a gamma counter and the raw data were translated into absolute amounts (μg/lens) via extrapolation from standards. Results: After 28 days, lysozyme uptake was significantly lower on BA lenses when incubated in Solution A (33.7 μg) compared to Solution B (56.2 μg), p0.05. LB lenses also deposited similar amounts of lysozyme for both solutions (Solution A: 5.0 μg, Solution B: 4.7 μg, p>0.05). After 28 days, BA lenses accumulated approximately twice the amount of lactoferrin than the other lens materials, with 30.3 μg depositing when exposed to Solution A and 22.0 μg with Solution B. The difference between the two solutions was statistically significant (p0.05. LB lenses also deposited similar amounts of lysozyme for both solutions (Solution A: 5.0 μg, Solution B: 4.7 μg, p>0.05). After 28 days, BA lenses accumulated approximately twice the amount of lactoferrin than the other lens materials, with 30.3 μg depositing when exposed to Solution A and 22.0 μg with Solution B. The difference between the two solutions was statistically significant (p0.05). After 28 days, albumin deposition onto BA lenses was significantly greater when lenses were incubated in Solution B (1.7 μg) compared to Solution A (0.9 μg), p0.05). LB lenses incubated in Solution A deposited more albumin compared to Solution B (0.9 μg versus 0.6 μg), p=0.003. Discussion: Protein deposition onto SH materials varied when contact lenses were incubated in either a complex ATS compared to a single protein solution. More lysozyme accumulated onto BA lenses incubated in a complex analog of the human tear film, whereas lactoferrin deposited onto SA lenses independent of incubation solution composition. To better mimic the ex vivo environment, future studies should use more appropriate analogs of the tear film. © 2012 Molecular Vision.

Leiske,D. L., Leiske,C. I., Leiske,D. R., Toney,M. F., Senchyna,M., Ketelson,H. A., Meadows,D. L., Srinivasan,S., Jones,L., Fuller,G. G. Temperature-induced transitions in the structure and interfacial rheology of human meibum Biophysical journal 2012;102(2):369-376 [ Show Abstract ]

Meibomian lipids are the primary component of the lipid layer of the tear film. Composed primarily of a mixture of lipids, meibum exhibits a range of melt temperatures. Compositional changes that occur with disease may alter the temperature at which meibum melts. Here we explore how the mechanical properties and structure of meibum from healthy subjects depend on temperature. Interfacial films of meibum were highly viscoelastic at 17°C, but as the films were heated to 30°C the surface moduli decreased by more than two orders of magnitude. Brewster angle microscopy revealed the presence of micron-scale inhomogeneities in meibum films at higher temperatures. Crystalline structure was probed by small angle x-ray scattering of bulk meibum, which showed evidence of a majority crystalline structure in all samples with lamellar spacing of 49 that melted at 34°C. A minority structure was observed in some samples with d-spacing at 110 that persisted up to 40°C. The melting of crystalline phases accompanied by a reduction in interfacial viscosity and elasticity has implications in meibum behavior in the tear film. If the melt temperature of meibum was altered significantly from disease-induced compositional changes, the resultant change in viscosity could alter secretion of lipids from meibomian glands, or tear-film stabilization properties of the lipid layer. © 2012 Biophysical Society.

Leiske,D. L., Miller,C. E., Rosenfeld,L., Cerretani,C., Ayzner,A., Lin,B., Meron,M., Senchyna,M., Ketelson,H. A., Meadows,D., Srinivasan,S., Jones,L., Radke,C. J., Toney,M. F., Fuller,G. G. Molecular structure of interfacial human meibum films Langmuir 2012;28(32):11858-11865

Liu,S., Jones,L., Gu,F. X. Development of Mucoadhesive Drug Delivery System Using Phenylboronic Acid Functionalized Poly(D,L-lactide)-b-Dextran Nanoparticles Macromolecular Bioscience 2012;12(12):1622-1626 [ Show Abstract ]

Mucoadhesive NP drug carriers have attracted substantial interest as a potential treatment for anterior eye diseases. NPs composed of PLA-Dex surface functionalized with a mucoadhesive ligand, PBA, were developed as drug carriers with particle sizes ranging from 25 to 28nm. Using CycA as a model drug, we showed that NPs encapsulated up to 13.7wt% CycA and exhibited sustained release for up to 5 d in vitro at a clinically relevant dose. We fine-tuned the PBA density on the NP surface to maximize the mucin-NP interaction without compromising the particle stability in vitro. This block copolymer conjugate may be useful to improve the bioavailability of topical formulations. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lorentz,H., Heynen,M., Khan,W., Trieu,D., Jones,L. The impact of intermittent air exposure on lipid deposition Optometry and Vision Science 2012;89(11):1574-1581 [ Show Abstract ]

PURPOSE: To analyze the impact of intermittent air exposure on the in vitro deposition of two radioactive lipids on various contact lens (CL) materials, using a custom-designed model blink cell. METHODS: Six different CL materials (balafilcon A, lotrafilcon B, comfilcon A, senofilcon A, etafilcon A, and omafilcon A) were mounted on the model blink cell pistons, which cycled the lenses in and out of a complex artificial tear solution (ATS) that contained a trace amount of C-cholesterol or C-phosphatidylcholine. For the short-term experiment, air-exposed lenses were continuously cycled in and out of the ATS for 10 h. Longer term incubations for 6 days were tested with lotrafilcon B and balafilcon A materials incubated in C-cholesterol ATS. The air-exposed CLs were cycled for 14 h then submerged for 10 h each day. For both experiments, the control lenses were submerged for the entire test period. After incubation, lenses were processed, and deposited masses were quantified. RESULTS: Exposure to air resulted in increased amounts of cholesterol deposited by 1.6 to 4.3 fold on omafilcon A, balafilcon A, comfilcon A, and senofilcon A (p ≤ 0.03) compared with submerged lenses. No differences in deposition were observed for etafilcon A and lotrafilcon B (p > 0.05). The longer term incubation of lotrafilcon B and balafilcon A showed statistically significant increases in cholesterol deposition for both air-exposed lens materials (p 0.05). CONCLUSIONS: This study found that lipid deposition profiles are CL material dependent and that intermittent air exposure can influence the mass of lipid deposited. Copyright © 2012 American Academy of Optometry.

Lorentz,H., Heynen,M., Tran,H., Jones,L. Using an in vitro model of lipid deposition to assess the efficiency of hydrogen peroxide solutions to remove lipid from various contact lens materials Current eye research 2012;37(9):777-786 [ Show Abstract ]

Purpose: To test the ability of two commercially available hydrogen peroxide disinfection solutions, one containing a surfactant and one without, to remove lipid from various contact lens materials using in vitro radiochemical experiments. Methods: Etafilcon A, senofilcon A and balafilcon A contact lens materials were incubated in an artificial tear solution (ATS) containing a mixture of lipids, proteins, mucin and either 14C-cholesterol or 14C-phosphatidylcholine for 8 h. Following incubation, the lenses were removed, rinsed, and placed for 16 h in either a surfactant-containing peroxide solution (ClearCare ®), a peroxide solution devoid of a surfactant (AOSept ®) or stored without solution (control). This process was repeated every day for 1 week. The lenses were extracted with a previously optimized extraction protocol, evaporated, re-suspended, fluor added and counted for their radioactive signals. Masses of lipids deposited were calculated based on standard calibration curves, the disinfection solutions were compared and repeated measures ANOVA and post hoc statistical analysis was completed using Statistica 9. Results: The results of this experiment found that daily disinfection with hydrogen peroxide solutions reduced the amount of cholesterol and phosphatidylcholine deposited on the three contact lens materials examined, however in many cases the reduction in deposition was less than 15% when compared to the control. Disinfection with the solution containing the surfactant (ClearCare), resulted in the least deposited cholesterol and phosphatidylcholine for all materials, however not all of the comparisons were statistically significant. Conclusions: Overall, ClearCare hydrogen peroxide disinfection solution containing Pluronic 17R4 removed the most lipid from lenses when compared to the non-surfactant containing AOSept or the control, for both lipids and all lens materials. However, the differences found were quite small at times and whether these differences are clinically significant are yet to be determined. © 2012 Informa Healthcare USA, Inc.

Lorentz,H., Heynen,M., Trieu,D., Hagedorn,S. J., Jones,L. The impact of tear film components on in vitro lipid uptake Optometry and Vision Science 2012;89(6):856-867 [ Show Abstract ]

Purpose. To analyze the influence of various tear film components on in vitro deposition of two lipids (cholesterol and phosphatidylcholine) on three contact lens materials. Methods. Etafilcon A, balafilcon A, and senofilcon A were incubated in four different incubation solutions for 3 or 14 days: an artificial tear solution containing lipids and proteins, a protein tear solution containing proteins and the lipid of interest, a lipid tear solution containing lipids and no proteins, and a single lipid tear solution containing the lipid of interest only. Each incubation solution contained one of the two radiolabeled lipids: C-cholesterol (C) or C-phosphatidylcholine (PC). After soaking, lenses were removed from the incubation solution, the lipids were extracted and quantified using a beta counter, and masses of lipid were calculated using standard calibration curves. Results. This experiment examined several different parameters influencing lipid deposition on contact lenses, including lens material, length of incubation, and the composition of the incubation solution. Overall, lipid deposited differently on different lens materials (p senofilcon > etafilcon. Incubation solution had a large impact on how much lipid was deposited (p < 0.00001), although cholesterol and phosphatidylcholine demonstrated different deposition patterns. Lipid deposition after 14 days of incubation was consistently greater than after 3 days (p < 0.02). Conclusions. This in vitro study demonstrates that C and PC deposition are cumulative over time and that silicone hydrogel materials deposit more lipid than group IV conventional hydrogel materials. It also clearly demonstrates that deposition of C and PC is influenced by the composition of the incubation solution and that in vitro models must use more physiologically relevant incubation solutions that mimic the natural tear film if in vitro data is to be extrapolated to the in vivo situation. © 2012 American Academy of Optometry.

Luensmann,D., Jones,L. Protein deposition on contact lenses: The past, the present, and the future Contact Lens and Anterior Eye 2012;35(2):53-64 [ Show Abstract ]

Proteins are a key component in body fluids and adhere to most biomaterials within seconds of their exposure. The tear film consists of more than >400 different proteins, ranging in size from 10 to 2360 kDa, with a net charge of pH 1-11. Protein deposition rates on poly-2-hydroxyethyl methacrylate (pHEMA) and silicone hydrogel soft contact lenses have been determined using a number of ex vivo and in vitro experiments. Ionic, high water pHEMA-based lenses attract the highest amount of tear film protein (1300 μg/lens), due to an electrostatic attraction between the material and positively charged lysozyme. All other types of pHEMA-based lenses deposit typically less than 100 μg/lens. Silicone hydrogel lenses attract less protein than pHEMA-based materials, with <10 μg/lens for non-ionic and up to 34 μg/lens for ionic materials. Despite the low protein rates on silicone hydrogel lenses, the percentage of denatured protein is typically higher than that seen on pHEMA-based lenses. Newer approaches incorporating phosphorylcholine, polyethers or hyaluronic acid into potential contact lens materials result in reduced protein deposition rates compared to current lens materials. © 2012 British Contact Lens Association.

Luensmann,D., Moezzi,A., Peterson,R. C., Woods,C., Fonn,D. Corneal staining and cell shedding during the development of solution-induced corneal staining Optometry and Vision Science 2012;89(6):868-874 [ Show Abstract ]

Purpose. This non-dispensing cross-over study was conducted to determine if lenses presoaked in Opti-Free RepleniSH (OFR) or ReNu MultiPlus (RMP) cause solution-induced corneal staining (SICS) and subsequent cell sloughing before the typical 2 h in vivo examination point. Methods. Study lenses (PureVision) were worn bilaterally by 13 participants for periods of 15, 30, 60, and 120 min using two different contralateral care regimen pairings. The lens worn on the test eye was soaked overnight in either OFR or RMP and the control eye in Clear Care (CC). After lens removal, corneal staining was rated on a scale of 0 (negligible) to 100 (severe) for four peripheral quadrants and the central region, and the differential global staining score was calculated by subtracting baseline staining scores. Following the staining assessment, corneal cells were collected from the ocular surface using a non-contact irrigation system to determine ocular cell shedding rates. Results. Differential global staining score with OFR was greater than CC with the differences being statistically significant at 30 and 60 min (p 0.05). Conclusions. SICS occurred earlier but to a significantly lower degree when PureVision lenses were presoaked in OFR compared with RMP, while lenses presoaked in CC did not cause SICS. Ocular surface cell shedding after lens removal was not impacted by lens wear durations of ≤2 h. © 2012 American Academy of Optometry.

Ng,A., Heynen,M., Luensmann,D., Jones,L. Impact of tear film components on lysozyme deposition to contact lenses Optometry and Vision Science 2012 [ Show Abstract ]

PURPOSE: To investigate the impact of lactoferrin and lipids on the kinetic deposition of lysozyme on silicone and conventional hydrogel lenses, using a complex artificial tear solution (ATS). METHODS: Two silicone hydrogel lenses (AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A) and two conventional hydrogel lenses (ACUVUE 2; etafilcon A and PROCLEAR; omafilcon A) were investigated. Lenses were incubated in four different solutions: a complex ATS consisting of various salts, lipids, proteins, and mucins, an ATS without lactoferrin (ATS w/o Lac), an ATS without lipids (ATS w/o Lip), and an ATS without lactoferrin and lipids (ATS w/o Lac & Lip), each containing 2% radiolabeled (125I) lysozyme (1.9 mg/ml). After each time point (4, 12 h and 1, 2, 3, 5, 7, 14, 21, 28 days), the amount of lysozyme per lens was quantified. RESULTS: After 28 days, lotrafilcon B lenses incubated in ATS deposited significantly less lysozyme (9.7 ± 1.4 μg) than when incubated in solutions not containing lactoferrin and lipids (more than 11.8 μg) (p < 0.001). Lysozyme uptake to senofilcon A lenses was higher in ATS w/o Lip (5.3 ± 0.1 μg) compared with other solutions (less than 3.9 μg) (p < 0.001). Etafilcon A lenses deposited the most lysozyme in all four solutions compared with the rest of the lens types (p < 0.001). For etafilcon A lenses, less lysozyme was deposited when incubated in ATS w/o Lip (588.6 ± 0.4 μg) compared with the other solutions (more than 642.6 μg) (p < 0.001). Omafilcon A lenses in ATS w/o Lac accumulated significantly less lysozyme (12.8 ± 1.0 μg) compared with the other solutions (more than 14.2 μg) (p < 0.001). CONCLUSIONS: An ATS containing lactoferrin and lipids impacts lysozyme deposition on both silicone and conventional hydrogel contact lenses. When performing in vitro experiments to study protein deposition on contact lenses, more complex models should be used to better mimic the human tear film.

Srinivasan,S., Menzies,K., Sorbara,L., Jones,L. Infrared imaging of meibomian gland structure using a novel keratograph Optometry and Vision Science 2012;89(5):788-794 [ Show Abstract ]

PURPOSE.: To examine the ability of a novel non-contact device (Keratograph 4) to image the meibomian gland (MG) structures and their morphological changes in the upper and lower eyelids. METHODS.: Thirty-seven participants (mean age 57.8 ± 8.5 years; 3 males and 34 females) completed the Ocular Surface Disease Index questionnaire to assess dryness symptoms. Meibum secretion quality score, number of blocked gland orifices, and meibum expressibility scores were assessed. The lower lid (LL) and upper lid (UL) of all subjects were everted and images of the MGs were taken using the Keratograph 4 (OCULUS). A MG dropout score (MGDS) due to complete or partial gland loss of both lids was obtained using a subjective 4-grade scoring system, and digital analysis of the images using ImageJ was performed. Presence of tortuosity and visible acinar changes of the MGs were also noted. RESULTS.: MGDS for both lids was significantly positively correlated with the Ocular Surface Disease Index score (r = 0.51; p < 0.05). The MGDS determined using the digital grading was also significantly positively correlated (UL: r = 0.68, p < 0.05; LL: r = 0.42, p < 0.05). The sum of the MGDS for both lids using the subjective grading scale was significantly different between the non-MGD and MGD group (1.3 ± 1.0 vs. 3.1 ± 1.1; p = 0.0004). MGDS assessment using the digital grading was significantly different between non-MGD (UL = 6%, LL = 8%) and MGD group (UL = 32%, LL = 42%; p = 0.001). Tortuous MG was observed only on the UL in 6% of the participants. Visible acinar changes were noted in 40% of the study participants. CONCLUSIONS.: Infrared meibography is now possible in a clinical setting using commercially available devices, and meibography can help determine differences in MG structure in subjects symptomatic of dry eye. Copyright © 2012 American Academy of Optometry.

Subbaraman,L. N., Glasier,M. -A, Varikooty,J., Srinivasan,S., Jones,L. Protein deposition and clinical symptoms in daily wear of etafilcon lenses Optometry and Vision Science 2012;89(10):1450-1459 [ Show Abstract ]

Purpose.: To determine the relationship between clinical signs and symptoms and protein deposition over 8 h of wear of etafilcon A lenses in symptomatic and asymptomatic contact lens wearers. Methods.: Thirty adapted soft contact lens wearers (16 symptomatic and 14 asymptomatic) were fitted with etafilcon A lenses. In vivo wettability, non-invasive tear break-up time, and subjective symptoms (vision, comfort, and dryness) were assessed at baseline and after 2, 4, 6, and 8 h. After 2, 4, 6, and 8 h time points, lenses were collected, and total protein, total lysozyme, and active lysozyme deposition were assessed. Results.: There was a significant reduction (p = 0.032) in the non-invasive tear break-up time at 8 h in both groups. In the symptomatic group, there was a significant reduction in subjective comfort and dryness ratings at 6 and 8 h measurement with respect to baseline (p 94% at 8 h). Pearson's correlations between subjective symptoms and protein deposition showed poor correlations for total protein/lysozyme and any subjective factor (r 0.05), and only weak correlations between dryness and % active lysozyme (r = 0.3 to 0.5 for all time points). However, stronger correlations were found between active lysozyme and subjective comfort (r = 0.6 to 0.7; p < 0.001). Conclusions.: In addition to investigating total protein deposited on contact lenses, it is of significant clinical relevance to determine the conformational state of the deposited protein. Copyright © 2012 American Academy of Optometry.

Varikooty,J., Keir,N., Simpson,T. Estimating tear film spread and stability through tear hydrodynamics Optometry and Vision Science 2012;89(8):e1119-e1124 [ Show Abstract ]

PURPOSE.: The stability and ease of spread of the tear-film over the contact lens surface may be an indicator of contact lens surface dewetting. The present in vivo methods of determining lens dewetting are complex. This study introduces a novel and objective way of determining the upward spread and stability of the tear-film through measurement of tear-film particle dynamics. METHODS.: Ten adapted contact lens wearers wore the same type of contact lens. Using a video camera mounted to a slit-lamp, the tear-film spread over the lens surface was recorded after a blink, at 8× magnification and capture rate of 30 frames per second, at morning after lens insertion, and after 8 h of lens wear. Images from 20 videos, without blinks and without an observable change in fixation were analyzed without any further postprocessing of the images. Using a customized calibrated ImageJ macro for particle tracking, the velocity of naturally occurring reflective particles was determined. The results were analyzed using the R program and ProFit. RESULTS.: The results established that the upward particle velocity was highest immediately after a blink and declined with time. The spread of the tear film measured through upward particle velocity was different on lens insertion than after 8 h of lens wear (p ≤ 0.001). The exponential time constants ± SE were 346.02 ± 29.0 for lens insertion at morning and 1413.13 ± 419.6 after 8 h of lens wear. CONCLUSIONS.: A novel and non-invasive way to measure in vivo spread and stability of the prelens tear-film has been developed. Additional studies are needed to understand whether this simple measure is able to differentiate the performance of different soft contact lenses and how this method may help in the understanding other aspects of lens performance such as non-invasive tear breakup time, surface deposition, and lens comfort. Copyright © 2012 American Academy of Optometry.

Weeks,A., Morrison,D., Alauzun,J. G., Brook,M. A., Jones,L., Sheardown,H. Photocrosslinkable hyaluronic acid as an internal wetting agent in model conventional and silicone hydrogel contact lenses Journal of Biomedical Materials Research - Part A 2012;100 A(8):1972-1982 [ Show Abstract ]

Photocrosslinkable methacrylated hyaluronic acid (HA) was prepared and incorporated into model conventional and silicone hydrogel contact lenses as an internal wetting agent. The molecular weight of the HA, the degree of methacrylation as well as the amount (0.25 to 1.0 wt %) incorporated were varied. The HA-containing hydrogels were analyzed using a variety of techniques including water contact angles, equilibrium water content (EWC), and lysozyme sorption. The presence of HA could be detected in the materials using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopya - attenuated total reflectance. The materials containing methacrylated HA had improved hydrophilicity and reduced lysozyme sorption. Effects of modified HA on EWC were dependent upon the materials but generally increased water uptake. Increased mobility of the HA associated with a lower molecular weight and lower degree of methacrylation was found to be more effective in improving hydrophilicity and decreasing lysozyme sorption than the less mobile HA. All results found suggest that photocrosslinkable HA has significant potential in contact lens applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012. Copyright © 2011 Wiley Periodicals, Inc.

Weeks,A., Subbaraman,L. N., Jones,L., Sheardown,H. The competing effects of hyaluronic and methacrylic acid in model contact lenses Journal of Biomaterials Science, Polymer Edition 2012;23(8):1021-1038 [ Show Abstract ]

The aim of this study was to determine the influence of hyaluronic acid (HA) on lysozyme sorption in model contact lenses containing varying amounts of methacrylic acid (MAA). One model conventional hydrogel (poly(2-hydroxyethyl methacrylate) (pHEMA)) and two model silicone hydrogels (pHEMA, methacryloxypropyltris(trimethylsiloxy)silane (pHEMA TRIS) and N,N-dimethylacrylamide, TRIS (DMAA TRIS)) lens materials were prepared with and without MAA at two different concentrations (1.7 and 5%). HA, along with dendrimers, was loaded into these model contact lens materials and then cross-linked with 1-ethyl-3-(3-dimethylamino propyl)-carbodiimide (EDC). Equilibrium water content (EWC), advancing water contact angle and lysozyme sorption on these lens materials were investigated. In the HA-containing materials, the presence (P < 0.05) and amount (P < 0.05) of MAA increased the EWC of the materials. For most materials, addition of MAA reduced the advancing contact angles (P < 0.05) and for all the materials, the addition of HA further improved hydrophilicity (P < 0.05). For the non-HA containing hydrogels, the presence (P < 0.05) and amount (P < 0.05) of MAA increased lysozyme sorption. The presence of HA decreased lysozyme sorption for all materials (P < 0.05). MAA appears to work synergistically with HA to increase the EWC in addition to improving the hydrophilicity of model pHEMA-based and silicone hydrogel contact lens materials. Hydrogel materials that contain HA have tremendous potential as hydrophilic, protein-resistant contact lens materials. © Koninklijke Brill NV, Leiden, 2012.

Woods,J., Jones,L., Woods,C., Schneider,S., Fonn,D. Use of a photographic manipulation tool to assess corneal vascular response Optometry and Vision Science 2012;89(2):215-220 [ Show Abstract ]

Purpose. Corneal vasculature change in contact lens wearers has been linked to the level of hypoxia within the cornea. To assess the impact a treatment has on limbal vessels, a sensitive method of measurement and quantification is required. Methods. A group of 21 highly myopic, hydrogel wearers, with preexisting signs of corneal hypoxia, were enrolled into a study where they wore sifilcon A silicone hydrogel lenses (Dk/t = 117), on a daily wear basis for 9 months. At all scheduled visits, photographs were taken of the superior, inferior, temporal, and nasal limbal regions which were then imported into Adobe Photoshop. A red-free filter was applied to enhance the contrast of the blood columns. In each quadrant, the length of the longest visible blood column was measured and the blood columns that penetrated -0.5 mm into the cornea were counted. A control group of 11 non-lens wearers was recruited. Their photographs were taken at the beginning of the study and 9 months later. An independent, masked observer assessed the photographs. Results. There was a significant decrease in the maximum penetration of the blood column in all quadrants (p + 0.001) from baseline to the 9-month visit (e.g., superior: baseline 0.84 ± 0.39 mm; 9 months 0.63 ± 0.20 mm). There was also significant reduction in the number of visible blood columns longer than 0.5 mm in each quadrant (p + 0.001) from baseline to 9 months in all quadrants (e.g., superior: baseline 14.0 ± 8.2; 9 months 6.5 ± 6.0). The control group showed no change over time for the maximum blood column length (p = 0.638) or the number of columns >0.5 mm (p = 0.341). Conclusions. A group of highly myopic subjects exhibited reduction in the maximum length and number of blood columns in the cornea when refit with a highly permeable silicone hydrogel material. The use of photography, along with Adobe Photoshop software, provides a reliable way of measuring corneal vascular responses over time. (Optom Vis Sci 2012;89:215-220). © 2012 American Academy of Optometry.

Young,G., Chalmers,R., Napier,L., Kern,J., Hunt,C., Dumbleton,K. Soft contact lens-related dryness with and without clinical signs Optometry and Vision Science 2012;89(8):1125-1132 [ Show Abstract ]

PURPOSE.: To report demographics, wearing patterns, and symptoms from soft contact lens (SCL) wearers with significant SCL-related dryness symptoms with and without significant ocular signs of dryness. METHODS.: In a multicenter, prospective observational clinical trial, symptomatic SCL wearers reported significant SCL-related dryness via self-administered questionnaire of frequency and intensity of dryness after a dry eye (DE) examination. DE etiology was assigned post hoc by an expert panel, and those with and without significant DE-related signs were analyzed by univariate logistic regression. Possible DE etiologies were aqueous tear deficiency, SCL-induced tear instability, meibomian gland dysfunction, or "other." Wearers without signs that qualified for any DE etiology were designated as No DE Signs (NDES). RESULTS.: Of the 226 SCL symptomatic wearers examined, 23% were without signs, 30% had aqueous tear deficiency, 25% had SCL-induced tear instability, 14% had meibomian gland dysfunction, and 8% had "other" diagnoses. The NDES wearers had significantly longer pre-lens break-up time (9.8 vs. 6.6 s, p < 0.0001), better lens wetting (3.4 vs. 2.4 0 to 4 scale, p < 0.0001), lower levels of film deposits on lenses (0.45 vs. 0.92, 0 to 4 scale, p < 0.0001), and of most slit lamp signs. The NDES wearers were significantly more likely to be male (36% vs.19%, p ≤ 0.013), were less likely to have deteriorating comfort during the day (81% vs. 97%, p ≤ 0.001), reported longer average hours of comfortable wear (11 ± 3 vs. 9 ± 4 h, p ≤ 0.014), had older contact lenses (18 ± 14 vs. 13 ± 12 days, p ≤ 0.029), and greater intensity of photophobia early and late in the day (p ≤ 0.043 and 0.021). CONCLUSIONS.: Symptoms of dryness in SCL wearers stem from a variety of underlying causes. However, nearly one-quarter of these symptomatic SCL wearers appear to be free of signs of dryness. The effective management of CL-related dryness requires a comprehensive range of clinical assessments and the use of a diverse range of management strategies. Copyright © 2012 American Academy of Optometry.

2011

Dalton,K., Sorbara,L. Fitting an MSD (Mini Scleral Design) rigid contact lens in advanced keratoconus with INTACS Contact Lens and Anterior Eye 2011;34(6):274-281

Dumbleton,K. A., Woods,C. A., Jones,L. W., Fonn,D. The relationship between compliance with lens replacement and contact lens-related problems in silicone hydrogel wearers Contact Lens and Anterior Eye 2011;34(5):216-222 [ Show Abstract ]

To evaluate the relationship between compliance with replacement frequency (RF) and contact lens (CL)-related problems in silicone hydrogel (SiHy) wearers. Methods: 501 SiHy wearers from seven optometry offices completed surveys regarding their lens wear and any CL related problems which they may have experienced in the preceding 12 months. File review was subsequently conducted at their optometry offices to confirm the information provided. Results: 49% of respondents were wearing 2-week replacement (2WR) and 51% 1-month replacement (1MR) SiHy lenses. 67% wore their lenses for longer than the manufacturers' recommended RF (MRRF) and 60% for longer than their optometrist's recommended RF (ORRF). The mean RF was 2.6× the MRRF for 2WR and 1.5× for 1MR wearers (p< 0.001) with median values of 31 and 37 days, respectively. Twenty-three percent reported signs or symptoms consistent with potential complications relating to CL wear. This rate was significantly higher for wearers who were non-compliant with the ORRF than compliant wearers (26% versus 18%, p= 0.028). It was also higher for those multipurpose solution users who reported never/almost never rubbing and rinsing their lenses when compared with those who did this every night (29% versus 17%, p= 0.007). Conclusions: Two thirds of the SiHy wearers did not comply with the MRRF and 2WR wearers stretched the replacement interval of their lenses to a greater degree than 1MR wearers. Failing to replace lenses when recommended and failing to rub and rinse lenses were associated with a higher rate of patient-reported CL problems. © 2011 British Contact Lens Association.

Dumbleton,K. A., Woods,M., Woods,C. A., Jones,L. W., Fonn,D. Ability of patients to recall habitual contact lens products and enhancement of recall using photographic aids Contact Lens and Anterior Eye 2011;34(5):236-240 [ Show Abstract ]

To determine the proportion of soft contact lens (CL) wearers who are able to recall their habitual products (lenses and care system) correctly from memory, and to evaluate the value of using photographic aids (PAs) to improve recall. Methods: 103 soft lens wearers attended 2 visits to investigate their habitual CL product use. At the first visit they were asked to recall which products they were using and then to identify their products from PAs. They returned for a second visit with their products for confirmation. Results: 51% correctly reported their lens brands from memory alone, which improved to 87% with the use of the PAs (p< 0.001). 41% correctly reported their habitual care system from memory alone, which improved to 80% with the use of PAs (p< 0.001). Females were better at recalling care system brand names than males (49% versus 27% correct, p= 0.040) and wearers with more than 1 year experience with their habitual CLs had better recall than those with up to 1 year experience (63% versus 27%, p= 0.014). Conclusion: Less than 50% of contact lens wearers were able to recall the names of their habitual lens and lens care products correctly from memory. PAs improved this recall significantly for both contact lenses and contact lens care systems. © 2011 British Contact Lens Association.

Efron,N., Morgan,P. B., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Soft toric contact lens prescribing in different countries Contact Lens and Anterior Eye 2011;34(1):36-38

Gorbet,M. B., Tanti,N. C., Crockett,B., Mansour,L., Jones,L. Effect of contact lens material on cytotoxicity potential of multipurpose solutions using human corneal epithelial cells Molecular Vision 2011;173458-3467 [ Show Abstract ]

Purpose: Multipurpose solutions (MPS) are used daily to clean and disinfect silicone hydrogel (SiHy) contact lenses. This in vitro study was undertaken to identify the potential for interaction between MPS, SiHy surface treatments, and lens materials, which may lead to changes in the response of human corneal epithelial cells (HCEC) to MPS-soaked lenses. Methods: The MPS tested were renu fresh (formerly known as ReNu MultiPlus; ReNu), OptiFree Express (OFX), OptiFree RepleniSH, SoloCare Aqua, and Complete Moisture Plus. The SiHy materials evaluated were lotrafilcon A, lotrafilcon B, comfilcon A, galyfilcon A, and balafilcon A (BA). MPS-soaked lenses were placed on top of adherent HCEC. The effect of MPS dilutions (0.1 to 10% final concentration in medium) was also characterized. Cell viability, adhesion phenotype and caspase activation were studied after 24-h cell exposure. OFX released from lenses was determined using UV absorbance. Results: A significant reduction in viability (between 30 to 50%) was observed with cells exposed to lenses soaked in ReNu and OFX. A significant downregulation of α3 and β1 integrins, with integrin expression ranging from 60% to 75% of control (cells with no lens), was also observed with OFX and ReNu-soaked lenses. With the exception of BA, all other lenses soaked in OFX resulted in significant caspase activation, whereby over 18% of cells stained positive for caspases. Minimal caspase activation was observed in cells exposed to ReNu and Solo soaked lenses. For both OFX and ReNu, exposing cells to at least a 5% dilution had a significant effect on viability and integrin expression. While Complete and Solo did not lead to reduction in viability, cells exposed to a 10% dilution showed reduced integrin expression down to less than 70% of control value. Comparing cell response to diluted MPS solutions and various MPS-soaked lenses showed that it is not possible to reliably use cell response to MPS dilution alone to assess MPS biocompatibility. Conclusions: Our results demonstrate that the reaction of HCEC to MPS are affected by the type of lenses the MPS is released from and may potentially be influenced by the surface treatment (or lack of it) of SiHy materials. © 2011 Molecular Vision.

Heynen,M., Lorentz,H., Srinivasan,S., Jones,L. Quantification of non-polar lipid deposits on senofilcon A contact lenses Optometry and Vision Science 2011;88(10):1172-1179

Kao,E. C. Y., McCanna,D. J., Jones,L. W. Utilization of in vitro methods to determine the biocompatibility of intraocular lens materials Toxicology in Vitro 2011;25(8):1906-1911

Keir,N. J., Simpson,T., Hutchings,N., Jones,L., Fonn,D. Outcomes of wavefront-guided laser in situ keratomileusis for hyperopia Journal of cataract and refractive surgery 2011;37(5):886-893 [ Show Abstract ]

Purpose: To determine the impact of wavefront-guided laser in situ keratomileusis (LASIK) for hyperopia on corrected distance visual acuity (CDVA), contrast sensitivity, and higher-order aberrations (HOAs). Setting: Centre for Contact Lens Research, University of Waterloo, Waterloo, Ontario, Canada. Design: Case series. Methods: This study comprised patients who had LASIK for hyperopia. The HOAs up to the 4th order (5.0 mm pupil) in right eyes were analyzed. Results: The study enrolled 31 patients. The preoperative mean values were sphere, +2.60 diopters (D) ± 1.15 (SD) (range +1.00 to +5.00 D); astigmatism, -0.87 ± 0.74 D (range 0.00 to -3.75 D); and spherical equivalent (SE), +2.16 ± 1.00 D (range +0.63 to +4.50 D). The postoperative refractive SE was within ±0.50 D in 71.0% of eyes. The uncorrected distance visual acuity was 20/20 or better in 87.2% of eyes. There was no significant change in CDVA or contrast sensitivity (all P>.05). There was a significant change in Zernike coefficients Z(0,4), Z(-1,3), Z(-3,3), and Z(3,3) (range of mean absolute change ± SEM: 0.092 ± 0.013 μm to 0.208 ± 0.018 μm; all P<.001). Coefficients Z(-1,3) and Z(3,3) increased and Z(0,4) and Z(-3,3) decreased in magnitude; each had a reversal of sign. The only significant postoperative association was between low-contrast CDVA and Z(0,4) (r = 0.617, P<.001). Conclusions: Low-contrast CDVA after LASIK surgery for hyperopia was correlated with Z(0,4). There were no significant changes in CDVA or contrast sensitivity. The relative risk for losing low-contrast CDVA increased if more than 1 Zernike term had a sign change. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2011 ASCRS and ESCRS.

Lorentz,H., Heynen,M., Kay,L. M. M., Dominici,C. Y., Khan,W., Ng,W. W. S., Jones,L. Contact lens physical properties and lipid deposition in a novel characterized artificial tear solution Molecular Vision 2011;173392-3405 [ Show Abstract ]

Purpose: To characterize various properties of a physiologically-relevant artificial tear solution (ATS) containing a range of tear film components within a complex salt solution, and to measure contact lens parameters and lipid deposition of a variety of contact lens materials after incubation in this ATS. Methods: A complex ATS was developed that contains a range of salts, proteins, lipids, mucin, and other tear film constituents in tear-film relevant concentrations. This ATS was tested to confirm that its pH, osmolality, surface tension, and homogeneity are similar to human tears and remain so throughout the material incubation process, for up to 4 weeks. To confirm that silicone hydrogel and conventional hydrogel contact lens materials do not alter in physical characteristics beyond what is allowed by the International Organization for Standardization (ISO) 18369-2. The diameter, center thickness, and calculated base curve were measured for five different lens materials directly out of the blister pack, after a rinse in saline and then following a two week incubation in the modified ATS. To test the ATS and the effect of its composition on lipid deposition, two lens materials were incubated in the ATS and a modified version for several time points. Both ATS solutions contained trace amounts of carbon-14 cholesterol and phosphatidylcholine, such that deposition of these specific lipids could be quantified using standard methods. Results: This ATS is a complex mixture that remains stable at physiologically relevant pH (7.3-7.6), osmolality (304- 306 mmol/kg), surface tension (40-46 dynes/cm) and homogeneity over an incubation period of three weeks or more. The physical parameters of the lenses tested showed no changes beyond that allowed by the ISO guidelines. Incubations with the ATS found that balafilcon A lenses deposit significantly more cholesterol and phosphatidylcholine than omafilcon A lenses (p<0.05) and that removing lactoferrin and immunoglobulin G from the ATS can significantly decrease the mass of lipid deposited. Conclusions: This paper describes a novel complex artificial tear solution specially designed for in-vial incubation of contact lens materials. This solution was stable and did not adversely affect the physical parameters of the soft contact lenses incubated within it and showed that lipid deposition was responsive to changes in ATS composition. © 2011 Molecular Vision.

Maram,J., Sorbara,L., Simpson,T. Accuracy of Visante and Zeiss-Humphrey Optical Coherence Tomographers and their cross calibration with optical pachymetry and physical references Journal of Optometry 2011;4(4):147-155

Menzies,K. L., Jones,L. In vitro analysis of the physical properties of contact lens blister pack solutions Optometry and Vision Science 2011;88(4):493-501 [ Show Abstract ]

Purpose. Since the initial development of silicone hydrogels, many modifications to the bulk and surface properties of the lenses have been undertaken to improve the wettability and comfort of the lenses. Recently, manufacturers have incorporated various "wetting agents" or surface-active agents into the blister packaging solutions (BPSs) of the lenses to improve initial comfort of the lens on eye. The purpose of this study was to measure and compare the pH, surface tension (ST), viscosity, and osmolality of BPSs for a variety of silicone hydrogel and polyHEMA-based hydrogel lenses. In addition, two saline solutions were tested for comparison purposes. Methods. The pH, osmolality, ST, and viscosity were measured for the BPSs for lotrafilcon B and lotrafilcon A and lotrafilcon B with a "modified BPS" (m-lotrafilcon A, m-lotrafilcon B) (CIBA Vision, Duluth, GA); balafilcon A (Bausch & Lomb, Rochester, NY); galyfilcon A, senofilcon A, and narafilcon A (Johnson & Johnson, Jacksonville, FL); and comfilcon A and enfilcon A (CooperVision, Pleasanton, CA) and BPSs from two conventional polyHEMA-based materials-etafilcon A (Johnson & Johnson) and omafilcon A (CooperVision). The two saline solutions tested were Unisol (Alcon, Fort Worth, TX) and Softwear Saline (CIBA Vision). Results. The pH results for the two saline solutions and all BPSs remained in the pH range of tears (6.6-7.8). The ST of the modified BPS was significantly lower (p 0.05) between BPSs made by the same manufacturer but were significantly different compared with BPSs made by different manufacturers (p < 0.05). Conclusions. The incorporation of wetting agents and surfactants into BPSs does alter the physical properties of the BPSs, which may have clinical implications regarding initial in-eye comfort. Copyright © 2011 American Academy of Optometry.

Moezzi,A. M., Fonn,D., Varikooty,J., Richter,D. Distribution of overnight corneal swelling across subjects with 4 different silicone hydrogel lenses Eye and Contact Lens 2011;37(2):61-65 [ Show Abstract ]

Purpose: To determine distribution of central corneal swelling (CCS) across subjects after 8 hr of sleep in eyes wearing silicone hydrogel lenses with various oxygen transmissibility (Dk/t) values and in eyes without lenses. Methods: Twenty-nine neophytes wore lotrafilcon A (Dk, 140), balafilcon A (Dk, 91), galyfilcon A (Dk, 60), and senofilcon A (Dk, 103) lenses in powers -3.00, -10.00, and +6.00 diopters on separate nights, in random order, and on 1 eye only. The contralateral eye (no lens) served as the control. Central corneal thickness was measured using a digital optical pachometer before lens insertion and immediately after lens removal on waking. Results: The average difference between the mean (7%) and the median (6.8%) CCS of all lenses was only 0.2%, suggesting a normal distribution. There was no correlation between the mean and the range of the CCS (r=0.058, P=0.766). Normal CCS distributions were also found with each lens-wearing eye and the control eye (P>0.20 for all). There was a significant correlation between lens-wearing eye and control eye (r=0.895, P<0.001) and between lotrafilcon A and each of the other 3 lenses for mean CCS across the study participants (P<0.001 for all). Conclusions: Distribution of corneal swelling in both lens-wearing eye and control eye followed a normal curve. An individual's corneal swelling response seems to be independent of lens type. © 2011 Lippincott Williams & Wilkins.

Morgan,P. B., Efron,N., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Global trends in prescribing contact lenses for extended wear Contact Lens and Anterior Eye 2011;34(1):32-35

Schulze,M. M., Hutchings,N., Simpson,T. L. Grading bulbar redness using cross-calibrated clinical grading scales Investigative Ophthalmology and Visual Science 2011;52(8):5812-5817 [ Show Abstract ]

Purpose. To determine the between-scale agreement of grading estimates obtained with cross-calibrated McMonnies/Chapman- Davies (MC-D), Institute for Eye Research (IER), Efron, and Validated Bulbar Redness (VBR) grading scales. Methods. Modified reference images of each grading scale were positioned on a desk according to their perceived redness (within a 0 to 100 range) as determined in a previous psychophysical scaling experiment. Ten observers were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Only 0 and 100 were marked on the scale, but not the numerical position of the reference images. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. Results. Overall, perceived redness depended on the sample image and the reference scale used (repeated measures ANOVA; P = 0.0008); six sample images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability ranged from five units (IER vs. VBR) to eight units (IER vs. Efron) of the 0 to 100 range. Conclusions. The use of cross-calibrated reference grades for bulbar redness grading scales allows comparison of grading estimates obtained with different scales. Perceived redness is dependent on the dynamic range of the reference images of the scale, with redness estimates generally being found to be higher for scales with a shorter dynamic range. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Sorbara,L., Maram,J., Bizheva,K., Hutchings,N., Simpson,T. L. Case report: Chalazion and its features visualized by ultrahigh resolution optical coherence tomography Contact Lens and Anterior Eye 2011;34(2):87-91

Subbaraman,L. N., Borazjani,R., Zhu,H., Zhao,Z., Jones,L., Willcox,M. D. P. Influence of protein deposition on bacterial adhesion to contact lenses Optometry and Vision Science 2011;88(8):959-966 [ Show Abstract ]

Purpose. The aim of the study is to determine the adhesion of Gram positive and Gram negative bacteria onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials with and without lysozyme, lactoferrin, and albumin coating. Methods. Four lens types (three SH-balafilcon A, lotrafilcon B, and senofilcon A; one CH-etafilcon A) were coated with lysozyme, lactoferrin, or albumin (uncoated lenses acted as controls) and then incubated in Staphylococcus aureus (Saur 31) or either of two strains of Pseudomonas aeruginosa (Paer 6294 and 6206) for 24 h at 37°C. The total counts of the adhered bacteria were determined using the H-thymidine method and viable counts by counting the number of colony-forming units on agar media. Results. All three strains adhered significantly lower to uncoated etafilcon A lenses compared with uncoated SH lenses (p 0.05). Lactoferrin coating on lenses increased binding (total and viable counts) of Saur 31 (p < 0.05). Lactoferrin-coated lenses showed significantly higher total counts (p < 0.05) but significantly lower viable counts (p < 0.05) of adhered P. aeruginosa strains. There was a significant difference between the total and viable counts (p < 0.05) that were bound to lactoferrin-coated lenses. Albumin coating of lenses increased binding (total and viable counts) of all three strains (p < 0.05). Conclusions. Lysozyme deposited on contact lenses does not possess antibacterial activity against certain bacterial strains, whereas lactoferrin possess an antibacterial effect against strains of P. aeruginosa. © 2011 American Academy of Optometry.

Szczotka-Flynn,L., Benetz,B. A., Lass,J., Albright,M., Gillespie,B., Kuo,J., Fonn,D., Sethi,A., Rimm,A. The association between mucin balls and corneal infiltrative events during extended contact lens wear Cornea 2011;30(5):535-542 [ Show Abstract ]

PURPOSE:: To determine the association between mucin ball formation and corneal infiltrative events (CIEs) during continuous wear with lotrafilcon A silicone hydrogel contact lenses. METHODS:: Subjects (n = 205) in the Longitudinal Analysis of Silicone Hydrogel Contact Lens Study wore lotrafilcon A contact lenses for 12 months of continuous wear. The primary outcome was a CIE. Kaplan-Meier methods were used to estimate the unadjusted cumulative incidence of remaining CIE free stratified by mucin ball presence. Cox proportional hazards regression was used to model the hazard of developing a CIE as a function of mucin ball formation and other covariates. RESULTS:: Over half (54.2%) of the subjects displayed some presence of mucin balls during at least 1 visit and about one third (32.8%) displayed repeated episodes. Mucin ball scores were correlated between the 2 eyes and weakly correlated with corneal curvature (P ≤ 0.005). Univariate analyses revealed that the relative hazard for a CIE was 0.35 [95% confidence interval (CI), 0.19-0.68] if a single episode of mucin balls was detected and 0.17 (95% CI, 0.06-0.43) if repeated episodes were detected. Upon multivariate analysis, repeated presence of mucin balls was associated with an 84% decreased hazard of experiencing a CIE (hazard ratio: 0.16; 95% CI, 0.06-0.44). CONCLUSIONS:: The presence of mucin balls is significantly associated with a decreased incidence of CIEs, and the effect is greatest when they are repeatedly present over time. We hypothesize that the mucin ball presence represents a more concentrated or viscous mucus layer, which prevents upregulation of the immune response against bacterial ligands. Copyright © 2011 by Lippincott Williams & Wilkins.

Tanti,N. C., Jones,L., Gorbet,M. B. Impact of multipurpose solutions released from contact lenses on corneal cells Optometry and Vision Science 2011;88(4):483-492 [ Show Abstract ]

Purpose. To assess, in vitro, the effect of the release of contact lens multipurpose solutions (MPS) from two silicone hydrogel lenses on human corneal epithelial cells. Methods. A monolayer of immortalized human corneal epithelial cells was seeded in a 24-well plate in keratinocyte serum-free medium. Lotrafilcon A (LA) and balafilcon A (BA) lenses were placed on top of the adherent cells for 8 and 24 h, after being soaked in MPS, borate-buffered (Unisol) or phosphate-buffered saline overnight. Cells were assayed for viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay or for α3, β1, and β4 integrin expression and caspase activation by flow cytometry. Results. After 8 h, LA lenses soaked in Unisol, Opti-Free Express (OFX), and ReNu MultiPlus (ReNu) showed decrease in cell viability. LA and BA soaked in Complete Moisture Plus (Complete) had similar viability at around 85% of control. After 24 h, a further decrease in viability was observed with all MPS-soaked lenses; LA soaked in OFX significantly reduced viability compared with Unisol-soaked lenses. In addition, reduced levels of integrin expression for lenses soaked in OFX and ReNu, and for BA soaked in Complete were observed. At 24 h, only LA soaked in OFX led to an increase in caspase activation. Conclusions. Our results indicate an increase in cytotoxicity with borate-based MPS solutions in vitro when compared with both phosphate-buffered saline and borate-exposed lenses, suggesting that biocides and/or additives play a role in the observed cell reaction. Moreover, the mechanism of in vitro solution-induced toxicity appeared to be mediated by lens type, suggesting differences in the preferential adsorption/release profile of certain compounds. Copyright © 2011 American Academy of Optometry.

Weeks,A., Luensmann,D.,Boone,A, Jones,L., Sheardown,H. Hyaluronic acid as an internal wetting agent in model DMAA/TRIS contact lenses 2011 1-10 [ Show Abstract ]

Model silicone hydrogel contact lenses, comprised of N,N-dimethylacrylamide and methacryloxypropyltris (trimethylsiloxy) silane, were fabricated and hyaluronic acid (HA) was incorporated as an internal wetting agent using a dendrimer-based method. HA and dendrimers were loaded into the silicone hydrogels and cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. The presence and location of HA in the hydrogels was confirmed using X-ray photoelectron spectroscopy and confocal laser scanning microscopy, respectively. The effects of the presence of HA on the silicone hydrogels on hydrophilicity, swelling behavior, transparency, and lysozyme sorption and denaturation were evaluated. The results showed that HA increased the hydrophilicity and the equilibrium water content of the hydrogels without affecting transparency. HA also significantly decreased the amount of lysozyme sorption (p < 0.002). HA had no effect on lysozyme denaturation in hydrogels containing 0% and 1.7% methacrylic acid (MAA) (by weight) but when the amount of MAA was increased to 5%, the level of lysozyme denaturation was significantly lower compared to control materials. These results suggest that HA has great potential to be used as a wetting agent in silicone hydrogel contact lenses to improve wettability and to decrease lysozyme sorption and denaturation.

Woods,C. A., Dumbleton,K., Jones,L., Fonn,D. Patient use of smartphones to communicate subjective data in clinical trials Optometry and Vision Science 2011;88(2):290-294 [ Show Abstract ]

Purpose. Various methods have been used in clinical trials to collect time-sensitive subjective responses, including study diaries, telephone interviews, and use of text messaging. However, all of these methods are limited by the uncertainty of when the participants enrolled in the study actually record their responses. This technical note reports on the utility of the BlackBerry smartphone to collect such data and why such a system provides advantages over other methods to report subjective ratings in clinical studies. Methods. The Centre for Contact Lens Research developed an on-line web-enabled system that permits participants to record and immediately transmit subjective rating scores in numerical form directly into a web-enabled database. This, combined with the utility of BlackBerrys, enabled time-specific e-mail requests to be sent to the study participants and then for that data to be simultaneously transmitted to the web-enabled database. This system has been used in several clinical trials conducted at the Centre for Contact Lens Research, in which data were collected at various times and in several specific locations or environments. Results. In the clinical trials conducted using this system, participants provided responses on 97.5% of occasions to the requests for data generated by the automated system. When the request was for data on a set date, this method resulted in responses of 84.1% of the time. Conclusions.The series of clinical trials reported here show the benefits of the utilization of the BlackBerry to collect time- or environment-sensitive data via a web-enabled system. Copyright © 2011 American Academy of Optometry.

Youn,H. -Y, McCanna,D. J., Sivak,J. G., Jones,L. W. In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells Molecular Vision 2011;17237-246

2010

Bitton,E., Jones,L., Simpson,T., Woods,C. Influence of the blink interval on tear meniscus height in soft contact lens and nonlens wearers Eye and Contact Lens 2010;36(3):156-163 [ Show Abstract ]

Purpose: Tear meniscus height (TMH) is an indirect measurement of tear film volume. This study investigated the temporal changes in the TMH during the blink interval in the morning (8-9 am) and at the end of the day (5-6 pm) in both soft contact lens (CL) and nonlens wearers (NLW). Methods: Fifty participants (25 CL; 25 NLW) were evaluated for their subjective symptoms, TMH, noninvasive break up time, and bulbar hyperemia at the am and pm visits on the same day. The TMH was measured at set intervals between 2 and 15 sec during the blink interval, using an optical coherence tomographer. Results: The NLW group revealed no changes in a variety of symptoms during the day, whereas the CL group reported an increase in dryness (P=0.03) and grittiness (P=0.02) over the day. For both groups, the TMH and calculated tear meniscus volume revealed lower values immediately after the blink and increased progressively afterwards, mainly due to reflex tearing. The am tear meniscus volume values tended to be higher than the pm values for both groups, but this was not significant (NLW P=0.13; CL P=0.82). Noninvasive break up time deteriorated during the day for both groups but was only significant for the CL group (P=0.002), whereas bulbar hyperemia revealed no statistically significant change for either group. Conclusions: Reflex tearing may play a substantial role in the TMH differences observed over the blink interval. Standardization of the time when a TMH measurement is performed will be valuable in comparing tear film clinical studies. Copyright © Contact Lens Association of Ophthalmologists, Inc.

Boone,A., Heynen,M., Joyce,E., Jones,L. Ex vivo protein deposition on bi-weekly silicone hydrogel contact lenses Optometry and Vision Science 2010;87(2):146

Caffery,B., Heynen,M. L., Joyce,E., Jones,L., Robert III,R., Senchyna,M. MUC1 expression in Sjogren's syndrome, KCS, and control subjects Molecular Vision 2010;161720-1727 [ Show Abstract ]

Purpose: To quantify and compare human mucin 1 (MUC1) protein and mRNA expression in tears and conjunctival epithelial cells collected from Sjogren's syndrome (SS), non-Sjogren's keratoconjunctivitus sicca (KCS) and non-dry eyed (NDE) control subjects. Methods: Seventy-six subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 KCS (confirmed by symptoms and Schirmer scores ≤10 mm) and 26 NDE. Tears were collected using an eyewash technique. Impression cytology was used to gather protein and mRNA from conjunctival epithelial cells. Soluble and membrane bound MUC1 were quantified via western blotting and MUC1 mRNA was quantified by real time qPCR. Results: The SS group demonstrated significantly higher concentrations of soluble MUC1 (0.12±0.11 [SS]; 0.013±0.02 [KCS; p=0.001]; 0.0023±0.0024 [NDE; p<0.001]) and MUC1 mRNA (3.18±1.44 [SS]; 1.79±1.18 [KCS; p<0.05]; 1.60±0.74 [NDE; p<0.05]) compared to both KCS and NDE groups. Soluble MUC1 expression was also higher in the KCS group compared to the NDE group (p=0.02), where as MUC1 mRNA expression was similar in both KCS and NDE groups. Membrane bound MUC1 expression differed only between the SS and NDE groups (0.005±-0.003 [SS]; 0.003±0.002 [NDE; p=0.002]). Conclusions: These results demonstrate that SS subjects express greater quantities of MUC1 protein and mRNA compared to both KCS and control subjects. Increased soluble MUC1 expression was also found in KCS subjects compared to controls. Membrane bound MUC1 was present in higher concentration in SS versus NDE only. These significant changes in MUC1 expression may represent compensatory or protective responses to chronic insult to the ocular surface. © 2010 Molecular Vision.

Dalton,K., Schneider,S., Sorbara,L., Jones,L. Confocal microscopy and optical coherence tomography imaging of hereditary granular dystrophy Contact Lens and Anterior Eye 2010;33(1):33-40

Dumbleton,K., Richter,D., Woods,C., Jones,L., Fonn,D. Compliance with contact lens replacement in Canada and the United States Optometry and Vision Science 2010;87(2):131-139 [ Show Abstract ]

PURPOSE.: To assess eye care practitioners (ECPs) recommendations for replacement frequency (RF) of silicone hydrogel (SH) and daily disposable (DD) lenses in Canada and the U.S. and to compare noncompliance (NC) with manufacturer recommended RF by the ECP and patient, and the reasons given for NC. METHODS.: Invitations to participate were sent by e-mail to ECPs in Canada and the U.S. Twenty patient surveys were sent to 420 ECPs, and 2232 eligible surveys were received from 216 ECPs (26% Canada, 74% U.S.). Questions related to patient demographics, lens type, wearing patterns, ECP instructions for RF, and actual patient RF. ECPs provided lens information and their recommendation for RF after the surveys were completed and sealed in envelopes. Responses were anonymous. RESULTS.: DD accounted for 18% (Canada) vs. 16% (U.S.) of wearers (p > 0.05); 35% (Canada) vs. 45% (U.S.) wore 2-week replacement SH (2WR; p = 0.011); and 47% (Canada) vs. 39% (U.S.) wore 1-month replacement SH (1MR) lenses (p = 0.025). Thirty-four percent (Canada) vs. 18% (U.S.) of ECPs recommended longer RFs than the manufacturer recommended RF for 2WR lens wearers (p 0.05) and were lowest for DD (13% Canada, 12% U.S.), followed by 1MR (33% Canada, 28% U.S.). The highest NC rates were with 2WR (50% Canada, 52% U.S.). The most frequent reason for NC with 2WR and 1MR was 'forgetting which day to replace lenses' (54% Canada, 53% U.S.) and in DD wearers 'to save money' (56% Canada, 29% U.S., p < 0.001). CONCLUSIONS.: 1MR lenses are more frequently prescribed in Canada. ECPs in Canada were NC with 2WR lenses more frequently than U.S. ECPs, but patient NC rates were the same in both countries for all lens types. ECP and patient NC rates were highest for 2WR lens wearers. Copyright © 2010 American Academy of Optometry.

Dumbleton,K., Woods,C., Jones,L., Richter,D., Fonn,D. Comfort and vision with silicone hydrogel lenses: Effect of compliance Optometry and Vision Science 2010;87(6):421-425 [ Show Abstract ]

PURPOSE. Silicone hydrogel (SH) lenses are usually replaced after 2 weeks (2W) or 1 month (1M); however, many patients do not comply with the manufacturers' recommended replacement frequency (MRRF). The purpose of this analysis was to investigate the effect of compliance with MRRF on comfort and vision in SH wearers. METHODS. As a part of a larger study investigating compliance with MRRF, patients were asked to rate their subjective comfort and vision from 0 (very poor) to 10 (excellent) in the morning, at the end of the day (EVE), when lenses were new, and needed replacing (NR). RESULTS. One thousand three hundred forty-four patients wore 2W replacement modality (2WR) (n = 717) or 1M replacement modality (1MR) (n = 617) SH lenses. Comfort and vision in the morning and when lenses are new were significantly higher than for EVE and NR (p < 0.001). Twenty-nine percent (95% confidence interval 25.3-32.4) of 1MR and 59% (95% confidence interval 55.5-62.7) of 2WR wearers were non-compliant with the MRRF. Compliance had a significant effect on EVE (p = 0.002, p = 0.008) and NR (p < 0.001, p < 0.001) comfort and vision. After accounting for compliance, EVE and NR comfort and EVE vision were higher for 1MR than 2WR (p = 0.015, p = 0.044, p = 0.019). CONCLUSIONS. Compliant patients had better EVE and NR comfort and vision than non-compliant patients, regardless of replacement modality. Optimal subjective performance with SH lenses seems to be facilitated by replacing lenses as recommended. Copyright © 2010 American Academy of Optometry.

Efron,N., Morgan,P. B., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Daily disposable contact lens prescribing around the world Contact Lens and Anterior Eye 2010;33(5):225-227

Efron,N., Morgan,P. B., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. International rigid contact lens prescribing Contact Lens and Anterior Eye 2010;33(3):141-143

Fonn,D. Editorial: Myopia control and new editorial board members Eye and Contact Lens 2010;36(4):189

Fonn,D. It's a new day Eye and Contact Lens 2010;36(3):139

Fonn,D. Just what do we mean by clinical significance Eye and Contact Lens 2010;36(1):1

Fonn,D. Editorial: Concerned parents and patients Eye and Contact Lens 2010;36(2):67

Fonn,D. What goes around comes around Eye and Contact Lens 2010;36(6):323

Fonn,D., Peterson,R., Woods,C. Corneal staining as a response to contact lens wear Eye and Contact Lens 2010;36(5):318-321 [ Show Abstract ]

Objective: To review the effects of contact lenses on the corneal surface. Methods: A review of the literature and in-house research of corneal staining and its various forms of presentation. Results: Corneal staining manifests in many different forms. The severity of staining or insult of the cornea is usually determined by the extent (area of coverage), density, and depth. The cause of staining is multifactorial, and its location is often linked to the type of lens that is being worn, the solution used to clean/disinfect the lens, the state of hydration of the soft lens, and the state of the cornea that has been affected by the lens. Conclusions: Sodium fluorescein dye effectively highlights corneal integrity changes referred to as corneal staining. This review describes the manifestations, the cause, the mechanisms, and the methods of remediation of corneal staining. © 2010 Lippincott Williams & Wilkins.

Gorbet,M. B., Tanti,N. C., Jones,L., Sheardown,H. Corneal epithelial cell biocompatibility to silicone hydrogel and conventional hydrogel contact lens packaging solutions Molecular Vision 2010;16272-282 [ Show Abstract ]

Purpose: Although all contact lenses (CLs) are applied initially to the eye directly from a packaging solution, little is known about the effects of these solutions on human corneal epithelial cells (HCECs). Due to the porous nature of CL materials, they have the potential to sorb components of the packaging solution during storage, which could then be subsequently released upon insertion of the CL on the eye. The purpose of this study was to investigate the effect of various packaging solutions on HCECs, using an in vitro model. Methods: An in vitro assay was developed whereby various silicone hydrogels and conventional, poly-2-hydroxyethylmethacrylate (polyHEMA)-based lens materials were removed directly from their packaging and then incubated for up to 24 h with HCECs. The effect of the retained and released packaging solution components on HCECs was assessed by measuring cell viability, adhesion phenotype, and apoptosis. Results: Incubation of HCECs with CLs stored in borate-buffered packaging solutions resulted in a significant reduction in cell viability. Adherent cells incubated with these CLs also exhibited reduced levels of β1 and α3 integrin. Soaking borate-buffered packaged CLs in PBS before cell incubation resolved viability and integrin expression in all cases, with the exception of galyfilcon A and balafilcon A, from which a 20% reduction in cell viability was still observed. In comparison, CLs stored in phosphate-buffered packaging solutions had cellular viability and expression of integrins similar to control cells (cells incubated in the absence of a lens). When incubated with cells at a 10% concentration in serum-free medium, borate-buffered packaging solutions and borate-containing saline (Unisol 4) significantly reduced cell viability and integrin expression. Neither caspase activation nor annexin V binding was observed on cells following exposure to borate buffer solution. However, a significant decrease in reactive oxygen species was observed at 24 h. These latter results suggest that in vitro exposure to low concentration of borate/boric acid results in cell dysfunction, leading to necrosis rather than apoptosis. Conclusions: Borate-buffered packaging solutions were shown to adversely affect the viability and integrin expression of HCECs in vitro. When used in ophthalmic packaging solutions, the antimicrobial properties of borate buffer may be outweighed by its relatively cytotoxic effects on cells. © 2010 Molecular Vision.

Hall,B. J., Jones,L. Contact lens cases: The missing link in contact lens safety? Eye and Contact Lens 2010;36(2):101-105 [ Show Abstract ]

Purpose: To summarize a variety of issues associated with contact lens case contamination and discuss appropriate methods that can limit this. Methods: A literature review was undertaken investigating the major factors associated with case contamination, with specific reference to the major pathogens associated with contamination, the role of bacterial biofilms, and methods that can limit contamination. Results: The use of antimicrobial cases, regular case cleaning and case replacement, avoidance of topping up solutions, and not using tap water to rinse cases all appear to be important in avoidance of significant case contamination. Conclusions: Contact lens case contamination is a significant public health concern and may contribute significantly to the development of microbial keratitis in contact lens wearers. Patients should be reminded that they must clean and disinfect their lens cases daily, should avoid the use of tap water for rinsing them, must not top up their solutions, must take into careful consideration where and how the cases are stored during the time that lenses are being worn and that they must be replaced regularly. The adoption of these methods will substantially reduce the levels of contamination of cases with pathogenic microbes. © 2010 Lippincott Williams & Wilkins.

Keech,A., Simpson,T., Jones,L. Repeatability of pachymetry and thinnest point localization using a Fourier-domain optical coherence tomographer Optometry and Vision Science 2010;87(10):736-741

Keir,N., Simpson,T., Fonn,D. Visual and optical performance of silicone hydrogel contact lenses for moderate myopia Journal of Optometry 2010;3(3):149-157 [ Show Abstract ]

Purpose: To compare the short-term visual and optical performance of silicone hydrogel contact lenses for myopia = -3.00D. Methods: This was a short-term, non-dispense, double-masked, randomized study investigating Night&Day (ND), PureVision (PV), O2 Optix (O2), Biofinity (BF), Acuvue Advance (AA) and Acuvue OASYS for myopia = -3.00D. Testing was conducted under scotopic conditions. Measures (one eye only) included: high- and low-contrast visual acuity (HCVA/LCVA), contrast sensitivity, subjective clarity of vision ratings (0-100 scale using reference images, with test image representing grade 50) and ocular aberrations (up to the 4th order, analyzed across individual scotopic pupil sizes). Results: Three males and 27 females participated, with a mean (± SD) age of 24.9 ± 7.7 yrs (range 19 to 53 yrs), sphere of -5.30 ± 1.73D (range -3.00 to -10.75D) and cylinder -0.36 ± 0.23D (range 0 to -0.75D). Mean (± SEM) logMAR HCVA ranged from 0.06 (PV) to 0.10 (AA) (± 0.02), LCVA from 0.33 (BF) to 0.40 (AA) (± 0.02) and contrast sensitivity from 2.33 (BF) to 2.53 (ND) (± 0.15) (differences not statistically significant; all p > 0.05). Subjective ratings for the test image ranged from 59 (PV) to 64 (ND) (± 4) and 56 (AA) to 65 (ND) (± 4), for monochromatic and polychromatic reference images, respectively (all p > 0.05). There was a statistically significant impact on ocular aberrations with all study lenses compared to no lens. Between-lens differences were statistically significant for defocus (Z 0 2), horizontal coma (Z 1 3) and spherical aberration (Z 0 4). Conclusions: Despite some differences in ocular aberrations, there were no significant differences in HCVA, LCVA, contrast sensitivity or subjective ratings across lenses. © 2010 Spanish General Council of Optometry. Published by Elsevier España, S.L. All rights reserved.

Keir,N., Woods,C. A., Dumbleton,K., Jones,L. Clinical performance of different care systems with silicone hydrogel contact lenses Contact Lens and Anterior Eye 2010;33(4):189-195

Luensmann,D., Heynen,M., Liu,L., Sheardown,H., Jones,L. The efficiency of contact lens care regimens on protein removal from hydrogel and silicone hydrogel lenses Molecular Vision 2010;16(10-11):79-92 [ Show Abstract ]

Purpose: To investigate the efficiency of lysozyme and albumin removal from silicone hydrogel and conventional contact lenses, using a polyhexamethylene biguanide multipurpose solution (MPS) in a soaking or rubbing/soaking application and a hydrogen peroxide system (H2O2). Methods: Etafilcon A, lotrafilcon B and balafilcon A materials were incubated in protein solutions for up to 14 days. Lenses were either placed in radiolabeled protein to quantify the amount deposited or in fluorescent-conjugated protein to identify its location, using confocal laser scanning microscopy (CLSM). Lenses were either rinsed with PBS or soaked overnight in H2O2 or MPS with and without lens rubbing. Results: After 14 days lysozyme was highest on etafilcon A (2,200 μg) >balafilcon A (50 μg) >lotrafilcon B (9.7 μg) and albumin was highest on balafilcon A (1.9 μg) =lotrafilcon B (1.8 μg) >etafilcon A (0.2 μg). Lysozyme removal was greatest for balafilcon A >etafilcon A >lotrafilcon B, with etafilcon A showing the most change in protein distribution. Albumin removal was highest from etafilcon A >balafilcon A >lotrafilcon B. H2O2 exhibited greater lysozyme removal from etafilcon A compared to both MPS procedures (p0.62). Albumin removal was solely material specific, while all care regimens performed to a similar degree (p>0.69). Conclusions: Protein removal efficiency for the regimens evaluated depended on the lens material and protein type. Overall, lens rubbing with MPS before soaking did not reduce the protein content on the lenses compared to nonrubbed lenses (p=0.89). © 2010 Molecular Vision.

Luensmann,D., Jones,L. Impact of fluorescent probes on albumin sorption profiles to ophthalmic biomaterials Journal of Biomedical Materials Research - Part B Applied Biomaterials 2010;94(2):327-336

Menzies,K. L., Jones,L. The impact of contact angle on the biocompatibility of biomaterials Optometry and Vision Science 2010;87(6):387-399 [ Show Abstract ]

Biomaterials may be defined as artificial materials that can mimic, store, or come into close contact with living biological cells or fluids and are becoming increasingly popular in the medical, biomedical, optometric, dental, and pharmaceutical industries. Within the ophthalmic industry, the best example of a biomaterial is a contact lens, which is worn by ∼125 million people worldwide. For biomaterials to be biocompatible, they cannot illicit any type of unfavorable response when exposed to the tissue they contact. A characteristic that significantly influences this response is that related to surface wettability, which is often determined by measuring the contact angle of the material. This article reviews the impact of contact angle on the biocompatibility of tissue engineering substrates, blood-contacting devices, dental implants, intraocular lenses, and contact lens materials. Copyright © 2010 American Academy of Optometry.

Menzies,K. L., Rogers,R., Jones,L. In vitro contact angle analysis and physical properties of blister pack solutions of daily disposable contact lenses Eye and Contact Lens 2010;36(1):10-18 [ Show Abstract ]

Objective: The purpose of this study was to measure the advancing and receding contact angles (CAs) of five daily disposable (DD) lenses and the osmolality, surface tension (ST), and pH of each blister pack solution. Methods: The advancing and receding CAs were measured directly out of the blister pack for five DD lenses: omafilcon A (CooperVision), nelfilcon A (CIBA Vision), modified nelfilcon A (CIBA Vision), etafilcon A (Johnson & Johnson), and narafilcon A (Johnson & Johnson). Advancing CAs were measured using sessile drop and Wilhelmy balance methods. Receding CAs were measured using the Wilhelmy balance method. ST, pH, and osmolality were measured for each blister pack solution from all the DD lenses. Results: The advancing CAs for the nelfilcon A lenses were statistically lower (P<0.05) than the advancing CAs of the other three lenses. The receding CAs for etafilcon A were statistically lower (P<0.05) than the receding CAs for the other four lenses. The pH of all the blister pack solutions was relatively neutral (7.01-7.43). The ST of the blister pack solution for the modified nelfilcon A was significantly lower (P<0.05) than the ST of all other blister pack solutions. The osmolality of the blister pack solutions for the etafilcon A and narafilcon A lenses were significantly higher (P<0.05) than the other blister pack solutions. Conclusions: The modified nelfilcon A lens had low advancing CAs and low receding CAs showing minimal hysteresis. The blister pack solution for the modified nelfilcon A lens had the lowest ST, a low osmolality, and a neutral pH. Copyright © Contact Lens Association of Ophthalmologists, Inc.

Morgan,P. B., Efron,N., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Twenty first century trends in silicone hydrogel contact lens fitting: An international perspective Contact Lens and Anterior Eye 2010;33(4):196-198

Morgan,P. B., Efron,N., Helland,M., Itoi,M., Jones,D., Nichols,J. J., van der Worp,E., Woods,C. A. Demographics of international contact lens prescribing Contact Lens and Anterior Eye 2010;33(1):27-29

Papas,E., Wolffsohn,J. S., Jones,L. Innovation in contact lenses: Basic research and clinical science Journal of Optometry 2010;3(3):123-124

Peterson,R. C., Fonn,D., Woods,C. A., Jones,L. Impact of a rub and rinse on solution-induced corneal staining Optometry and Vision Science 2010;87(12):1030-1036 [ Show Abstract ]

Purpose.: To investigate whether the inclusion of a rub and rinse step before contact lens disinfection has an impact on solution-induced corneal staining. Methods.: This was a prospective, double-masked, single investigator study. Twenty participants were recruited for two visits, where balafilcon-A lenses were worn bilaterally for 2 h. Each pair of lenses was prepared using two different methodologies. The "control" lens was transferred from the blister pack directly into a storage case containing polyhexamethylene biguanide-based lens care solution. The contralateral "test" lens was rubbed and simultaneously rinsed using the same polyhexamethylene biguanide-based care solution, for either 60 s (visit 1) or 20 s (visit 2). Both lenses were then soaked in the solution overnight. After baseline corneal staining assessments, the lenses were inserted following a randomized contralateral model. After 2 h, lenses were removed, corneal staining was regraded, and comfort scores were obtained. Results.: Rubbed and rinsed test lenses induced significantly less corneal staining than control lenses for all participants during visit 1 (mean ± SD: 516 ± 843 vs. 2170 ± 902; p 0.05). Conclusions.: Corneal staining induced after 2 h of lens wear with the combination of balafilcon-A and polyhexamethylene biguanide-based lens care solution can be significantly reduced by including a rub and rinse step before overnight soaking. Further work is required to establish the longevity of this effect during the monthly wearing cycle. Copyright © 2010 American Academy of Optometry.

Schulze,M. M., Hutchings,N., Simpson,T. L. The conversion of bulbar redness grades using psychophysical scaling Optometry and Vision Science 2010;87(3):159-167

Situ,P., Simpson,T. L. Interaction of corneal nociceptive stimulation and lacrimal secretion Investigative Ophthalmology and Visual Science 2010;51(11):5640-5645

Situ,P., Simpson,T. L., Jones,L. W., Fonn,D. Effects of silicone hydrogel contact lens wear on ocular surface sensitivity to tactile, pneumatic mechanical, and chemical stimulation Investigative Ophthalmology and Visual Science 2010;51(12):6111-6117 [ Show Abstract ]

PURPOSE. To determine the effects of silicone hydrogel lens wear and lens-solution interactions on ocular surface sensitivity. METHODS. Forty-eight adapted lens wearers completed the study, which comprised two phases. Phase 1 included habitual lens wear, no lens wear (7 ± 3 days), and balafilcon A lenses (PV; PureVision; Bausch & Lomb, Rochester, NY) with a hydrogen peroxide-based regimen for 2 weeks; phase 2 included wear of PV with the use of a multipurpose solution containing either polyhexamethylene-biguanide (PHMB) or Polyquad/Aldox (Alcon Laboratories, Fort Worth, TX) preservative, each for 1 week, with a 2-week washout period between solutions. Tactile and pneumatic (mechanical and chemical) stimuli were delivered, and thresholds were determined by Cochet-Bonnet (Luneau Ophthalmologie, Chartres, France) and Belmonte (Cooperative Research Centre for Eye Research and Technology, Sydney, NSW, Australia) pneumatic esthesiometers, respectively. Corneal and conjunctival thresholds and staining scores were assessed at baseline, after 2 and 8 hours of lens wear on day 1 and at the end of each wearing cycle (2 hours). RESULTS. In phase 1, compared to the no-lens baseline, corneal tactile thresholds increased at the 1-day, 8-hour and the 2-week visits (P < 0.05), whereas conjunctival mechanical thresholds decreased at the 1-day, 2-hour and the 2-week visits (P < 0.05). In phase 2, the chemical thresholds were lower with PHMBpreserved solution compared with the Polyquad/Aldox system at the 1-day, 2-hour and the 1-week visits (P < 0.05). Staining scores correlated inversely with conjunctival chemical thresholds (all P < 0.05). CONCLUSIONS. Ocular surface sensitivity changed in adapted lens wearers, when lenses were refit after a no-lens interval and during lens wear with different care regimens. The corneal staining that was observed with certain lens-solution combinations was accompanied by sensory alteration of the ocular surface-that is, higher levels of staining correlated with increased conjunctival chemical sensitivity. © Association for Research in Vision and Ophthalmology.

Sorbara,L., Dalton,K. The use of video-keratoscopy in predicting contact lens parameters for keratoconic fitting Contact Lens and Anterior Eye 2010;33(3):112-118

Sorbara,L., Maram,J., Fonn,D., Woods,C., Simpson,T. Metrics of the normal cornea: Anterior segment imaging with the Visante OCT Clinical and Experimental Optometry 2010;93(3):150-156 [ Show Abstract ]

Purpose: The purpose of the study was to obtain anterior segment biometry for 40 normal eyes and to measure variables that may be useful to design large diameter gas permeable contact lenses that sit outside the region normally viewed by corneal topographers. Also, the distribution of these variables in the normal eye and how well they correlated to each other were determined. Methods: This is a cross-sectional study, in which data were collected at a single study visit. Corneal topography and imaging of the anterior segment of the eye were performed using the Orbscan II and Visante OCT. The variables that were collected were horizontal K reading, central corneal/scleral sagittal depth at 15 mm chord, and nasal and temporal angles at the 15 mm chord using the built-in software measurement tools. Results: The central horizontal K readings for the 40 eyes were 43 ± 1.73 D (7.85 ± 0.31 mm), with ± 95% confidence interval (CI) of 38.7 (8.7 mm) and 46.6 D (7.24 mm). The mean corneal/scleral sagittal depth at the 15 mm chord was 3.74 ± 0.19 mm and the range was 3.14 to 4.04 mm. The average nasal angle (which was not different from the temporal angle) at the 15 mm chord was 39.32 ± 3.07 degrees and the ± 95%CI was 33.7 and 45.5 degrees. The correlation coefficient comparing the K reading and the corneal/scleral sagittal depth showed the best correlation (0.58, p < 0.001). The corneal/scleral sagittal depth at 15 mm correlated less with the nasal angle (0.44, p = 0.004) and the weakest correlation was for the nasal angle at 15 mm with the horizontal readings (0.32, p = 0.046). Conclusion: The Visante OCT is a valuable tool for imaging the anterior segment of the eye. The Visante OCT is especially effective in providing the biometry of the peripheral cornea and sclera and may help in fitting GP lenses with a higher percentage of initial lens success, when the corneal sag and lens sag are better matched. © 2010 The Authors. Journal compilation © 2010 Optometrists Association Australia.

Srinivasan,S., Joyce,E., Boone,A., Simpson,T., Jones,L., Senchyna,M. Tear lipocalin and lysozyme concentrations in postmenopausal women Ophthalmic and Physiological Optics 2010;30(3):257-266

Subbaraman,L. N., Jones,L. Kinetics of lysozyme activity recovered from conventional and silicone hydrogel contact lens materials Journal of Biomaterials Science, Polymer Edition 2010;21(3):343-358

Varikooty,J., Keir,N., Woods,C. A., Fonn,D. Measurement of the refractive index of soft contact lenses during wear Eye and Contact Lens 2010;36(1):2-5 [ Show Abstract ]

Purpose: To determine whether the refractive index (RI) of a soft contact lens can be evaluated using refractometry while the lens remains on the eye and to compare this with more traditional ex vivo RI measurements. Methods: A slitlamp apparatus was modified to incorporate a customized Atago hand refractometer. With a double-masked study design, nine adapted symptomatic soft contact lens wearers wore a contact lens in each eye (lotrafilcon B and etafilcon A) in a randomized order. In vivo RI was determined from the relative Brix scale measurements immediately after lens insertion and after 1 and 10 hr of lens wear. Ex vivo refractometry was performed after 10 hr of lens wear for comparison. Means ± standard errors of the means are reported. Results: In vivo RI values at baseline were 1.422 ± 0.0004 (lotrafilcon B) and 1.405 ± 0.0021 (etafilcon A); after 1 hr of lens wear, values were 1.423 ± 0.0006 and 1.408 ± 0.0007, respectively; and after 10 hr of lens wear, values were 1.424 ± 0.0004 and 1.411 ± 0.0010, respectively. Ex vivo RI values at the end of the 10 hr wearing period were 1.424 ± 0.0003 (lotrafilcon B) and 1.412 ± 0.0017 (etafilcon A). The change in in vivo RI across the day was statistically significant for the etafilcon A lens (repeated-measures analysis of variance, P0.05). Conclusions: This novel adaptation of refractometry was able to measure the RI of soft contact lenses during wear (without lens removal). End of day RI measurements using in vivo and ex vivo refractometry were comparable with each other. Future work is required to determine whether this in vivo method can improve our understanding of the relationships between soft contact lens RI, hydration, on-eye lens performance, and symptomology. Copyright © Contact Lens Association of Ophthalmologists, Inc.

2009

Boone,A., Heynen,M., Joyce,E., Varikooty,J., Jones,L. Ex vivo protein deposition on bi-weekly silicone hydrogel contact lenses Optometry and Vision Science 2009;86(11):1241-1249 [ Show Abstract ]

Purpose. This study investigated the protein deposition that occurs on daily wear silicone hydrogel (SH) lenses, after 2 weeks of wear. Methods. A total of 40 subjects were divided into equal groups, based on their habitual SH contact lens [CIBA Vision O2OPTIX (O2); Johnson & Johnson ACUVUE ADVANCE with HYDRACLEAR (ADV); Bausch & Lomb PureVision (PV); CIBA Vision Night & Day (ND)]. A randomized, double-masked, cross-over study was conducted in which subjects wore either their habitual SH material or Johnson & Johnson ACUVUE OASYS with HYDRACLEAR PLUS (OAS) for 2 weeks. At the end of the 2-week period, lenses were collected for analysis of total protein, total lysozyme, and percent denatured lysozyme. Results. Total protein was greatest for PV (33 ± 6 μg/lens), with other lenses depositing 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 μg/lens), with other lenses depositing 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 μg/lens), with other lenses depositing 0.05). Total lysozyme was also greatest for the PV lens (11 ± 3 μg/lens), with other lenses depositing 0.05). The percentage of lysozyme that was denatured was greatest for ND (90 ± 8%) and lowest for PV (23 ± 10%). The lysozyme extracted from ND and O2 lenses was significantly more denatured than that extracted from the other lens materials (p 0.05) or between ADV, OAS, and PV (p > 0.05). The amount of denatured lysozyme/lens was <3 μg/lens for all materials. Lysozyme as a percentage of the total protein deposited ranged from 32 (PV) to 6% (O2). Conclusions. This study confirms that all SH lenses deposit low levels of protein, and that the amount and percentage of denatured lysozyme can vary, depending on the overall surface charge of the material and absence or type of surface treatment. © 2009 American Academy of Optometry.

Boone,A., Hui,A., Jones,L. Uptake and release of dexamethasone phosphate from silicone hydrogel and FDA group I, II, and IV hydrogel contact lenses Eye and Contact Lens 2009;35(5):260-267 [ Show Abstract ]

OBJECTIVES: To investigate the uptake and release kinetics of the synthetic glucocorticoid anti-inflammatory drug dexamethasone into various conventional and silicone hydrogel contact lens materials. METHODS: Three conventional and six silicone hydrogel lenses were used in this study. A 0.1% dexamethasone solution was formulated and used to dope the various contact lens materials. The uptake and release of the drug was measured using a UV-visible light spectrophotometer at various time points during a period of 24 hr for each phase. RESULTS: Statistical analysis showed that all lenses took up a significant amount of dexamethasone. Alphafilcon A and lotrafilcon A showed the greatest uptake of dexamethasone, at 118 +/- 10 microg/lens and 102 +/- 11 microg/lens, respectively, and galyfilcon took up the least amount of drug at 34 +/- 6 microg/lens. The release of the drug from the lens materials was also statistically significant. The majority of the lenses released between 20 and 30 microg/lens, except for alphafilcon A and lotrafilcon A, which released a statistically different amount of drug when compared with the other lens materials. Alphafilcon A released 65 +/- 1.3 microg/lens, whereas lotrafilcon A slowly released only 11 +/- 0.2 microg/lens. CONCLUSIONS: Although most of the lenses released enough drug to have anti-inflammatory action, none of the materials released drug for a long enough period of time to be clinically useful as a drug delivery device.

Chow,L. M., Subbaraman,L. N., Sheardown,H., Jones,L. Kinetics of in vitro lactoferrin deposition on silicone hydrogel and FDA group II and group IV hydrogel contact lens materials Journal of Biomaterials Science, Polymer Edition 2009;20(1):71-82 [ Show Abstract ]

The aim of this study was to compare the kinetics of lactoferrin deposition on silicone hydrogel (SH) and conventional FDA group II and group IV hydrogel contact lens materials. Seven lens materials, two conventional (etafilcon A, FDA group IV; omafilcon A, FDA group II) and five SH (lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A and senofilcon A), were incubated in 1 ml (125)I-labeled lactoferrin solution for time periods ranging from 1 h to 28 days. At the end of specified incubation periods radioactive counts were determined on the lenses using an Automatic Gamma Counter. There was a gradual increase in lactoferrin deposition on all the lenses across all time points. At the end of 28 days the amount of lactoferrin/lens in microg was 11.3 +/- 1.9 for etafilcon A, 6.8 +/- 2.0 for omafilcon A, 2.1 +/- 0.9 for lotrafilcon A, 3.1 +/- 1.0 for lotrafilcon B, 11.8 +/- 2.9 for balafilcon A, 5.4 +/- 1.1 for galyfilcon A and 5.6 +/- 0.6 for senofilcon A. After 28 days, etafilcon A and balafilcon A deposited lactoferrin to the greatest degree (P < 0.05), but these were not different from each other (P = 0.48), while lotrafilcon A and B deposited the least (P < 0.05 vs. other lenses; P = 0.57 with each other). Galyfilcon A, senofilcon A and omafilcon A (P < 0.05 compared with other lenses; P > 0.05 with each other) deposited intermediate levels of lactoferrin. We concluded that radiochemical analysis is a sensitive and effective technique to determine the small quantities of lactoferrin deposited on SH lenses. The kinetics of lactoferrin deposition on contact lens materials depend on the chemical structure of the lens material.

Dumbleton,K., Woods,C., Fonn,D. An investigation of the efficacy of a novel ocular lubricant Eye and Contact Lens 2009;35(3):149-155 [ Show Abstract ]

OBJECTIVE: To investigate the efficacy of a novel ocular lubricant compared with a commercially marketed ocular lubricant in a group of noncontact lens wearers currently using over-the-counter products for the management of symptoms of moderate to severe dry eye. METHODS: This was a prospective, double-masked study that randomized 110 subjects in a ratio of 1:1 to receive a novel ocular lubricant (test group) or a marketed ocular lubricant (control group). Subjects were instructed to instill the lubricant eye drops at least three times daily. After enrollment, subjects were evaluated at baseline and at 7 and 30 days. They were also required to complete a series of home-based subjective questionnaires after 15 days. Main outcomes were subjective symptoms and objective clinical assessment at 7 and 30 days. RESULTS: The test group had higher overall comfort ratings than the control group (P = 0.012). Seventy-one percent of the test group and 57% of the control group said the drops used "somewhat" or "definitely" improved ocular comfort; 62% of the test group had greater end-of-day comfort compared with 45% of the control group (P = 0.015). There were no between-group differences in visual acuity, tear quality or quantity, corneal staining, conjunctival staining, or bulbar and limbal conjunctival hyperemia. CONCLUSIONS: The novel ocular lubricant offers equivalent or superior comfort compared with a marketed lubricant eye drop. Objective clinical outcomes were not statistically significantly different between the two groups. © 2009 Lippincott Williams & Wilkins.

Dumbleton,K., Woods,C., Jones,L., Fonn,D., Sarwer,D. B. Patient and practitioner compliance with silicone hydrogel and daily disposable lens replacement in the United States Eye and Contact Lens 2009;35(4):164-171 [ Show Abstract ]

OBJECTIVE: The objectives of this study were to assess current recommendations for replacement frequency (RF) of silicone hydrogel (SH) and daily disposable (DD) lenses, to determine compliance with these recommendations, and to investigate the reasons given for noncompliance. METHODS: A package containing 20 patient surveys was sent to 309 eye care practitioners (ECPs) in the United States who had agreed to participate in the study. One thousand eight hundred fifty-nine completed surveys were received from 158 ECPs and 1,654 surveys were eligible for analysis. Questions related to patient demographics, lens type, lens wearing patterns, the ECP instructions for RF, and the actual patient reported RF. ECPs were asked to provide lens information and their recommendation for RF after the surveys had been completed and sealed in envelopes. All responses were anonymous. RESULTS: Sixty-six percent of patients were women and their mean age was 34 ± 12 years. Eighty-eight percent of lenses were worn for daily wear, 12.8 ± 3.2 hours a day, 6.2 ± 1.5 days a week. Lens type distribution was 16% DD, 45% 2 week (2W) SH, and 39% 1 month (1M) SH. ECP recommendations for RF varied according to the lens type; 1% of 1M (95% CI 0.2-1.7), 4% of DD (95% CI 2.1-7.2), and 18% of 2W (95% CI 15.1-20.7) patients were given instructions that did not conform to the manufacturers' recommended RF (MRRF). When considering only those patients who were given the correct instructions for RF, 38% were not compliant with the MRRF; noncompliance rates varied according to the lens type and were 12% for DD (95% CI 8.6-17.2), 28% for 1M (95% CI 24.9-32.1), and 52% for 2W (95% CI 47.8-55.8). The most frequent reasons for over wearing lenses were "forgetting which day to replace lenses" (51%) and "to save money" (26%). Fifty-three percent believed that a reminder system would aid compliance; the most popular methods being a cell phone reminder or text message (29%) and a nominated day each week or month (26%). Discussions between the ECPs and the patients were more extensive for patients who were compliant with the MRRF. CONCLUSIONS: ECPs recommended RFs more frequently with DD and 1M SH lenses than with 2W SH lenses, consistent with manufacturers' recommendations. Patients were less compliant with RF than ECPs for all lens types investigated. Patients were most compliant with RF when wearing DD lenses and least compliant when wearing 2W SH lenses. Better communication facilitated greater compliance with RF. More than half of those not replacing lenses, when recommended, reported that this was because they forgot which day to replace their lenses. © 2009 Lippincott Williams & Wilkins, Inc.

Keech,A., Flanagan,J., Simpson,T., Jones,L. Tear meniscus height determination using the OCT2 and the RTVue-100 Optometry and Vision Science 2009;86(10):1154-1159 [ Show Abstract ]

PURPOSE: To compare anterior segment spectral-domain optical coherence tomography (SOCT) tear meniscus height (TMH) measures with those from the more commonly used time-domain OCT (TOCT). METHODS: The right eye of 50 healthy subjects had images of their TMH captured with TOCT (OCT2) and SOCT (RTVue-100). Data were acquired using two different anterior segment lenses, the cornea/anterior module-short (CAM-S) and long (CAM-L), on the SOCT. Images were then analyzed for differences in their derived TMH. RESULTS: The average TMH for TOCT was 0.280 ± 0.139 mm, whereas the mean TMH measured using the SOCT was 0.354 ± 0.163 mm and 0.345 ± 0.167 mm for the CAM-S and CAM-L, respectively. There was a significant difference (p < 0.001) when comparing TOCT with either of the SOCT lenses. There was no statistically significant difference between the CAM-L and CAM-S (p = 1.0). Bland-Altman analysis showed poor agreement between TOCT and SOCT (95% limits of agreement -0.138 to + 0.285 mm for the CAM-S and -0.185 to +0.315 mm for the CAM-L). CONCLUSIONS: The RTVue-100 produces TMH measurements that are significantly higher than OCT2 in a normal patient population. However, the RTVue-100 showed a number of other advantages over the OCT2 in the measurement and analysis of images. Future work needs to determine the causative factors behind the observed differences.

Keir,N. J., Simpson,T., Jones,L. W., Fonn,D. Wavefront-guided LASIK for myopia: Effect on visual acuity, contrast sensitivity, and higher order aberrations Journal of Refractive Surgery 2009;25(6):524-533 [ Show Abstract ]

PURPOSE: To determine the impact of wavefrontguided LASIK for myopia with or without astigmatism on high and low contrast best spectacle-corrected visual acuity (BSCVA), photopic and mesopic contrast sensitivity, and higher order aberrations. METHODS: Bilateral wavefront-guided LASIK (LADARVision4000; Hansatome microkeratome) was performed on 324 eyes (162 patients) with a mean spherical manifest refraction of -2.84±1.35 diopters (D) (range: -0.25 to -6.50 D) and astigmatism of -0.81±0.74 D (range: 0 to -4.00 D). Mean age was 37.7±9.3 years (range: 20 to 60 years). Best spectacle-corrected visual acuity and contrast sensitivity were assessed using ETDRS charts and vertical sinusoidal gratings, respectively. Higher order aberrations were measured using a Shack-Hartmann wavefront sensor, analyzed across a 5-mm pupil. Repeated measures and post hoc analyses determined statistical significance (P<.0025). Only right eyes were analyzed. RESULTS: One hundred thirty-six eyes (84%) had uncorrected visual acuity of 20/20 or better 6 months postoperative; 80.9% (131 eyes) were within ±0.50 D of attempted correction. Statistically significant postoperative improvements were noted in high and low contrast BSCVA (both P≤.001); in photopic contrast sensitivity at 3, 6, and 12 cycles per degree (cpd); and in mesopic contrast sensitivity at 12 and 18 cpd (all P<.001). With respect to higher order aberrations, a statistically significant change was seen in Zernike coefficients Z 3 -1, Z 3 1, Z 3 -3, Z 3 3, and Z 3 4 following surgery (range of mean absolute change: 0.042 to 0.142 μm; all P<.001). All increased in magnitude except for Z 3 -3, which decreased. CONCLUSIONS: Despite an increase in higher order aberrations, wavefront-guided LASIK yields excellent visual acuity and contrast sensitivity. Spherical aberration, which increases the most following non-wavefront-guided LASIK, showed no significant change.

Luensmann,D., Heynen,M., Liu,L., Sheardown,H., Jones,L. Determination of albumin sorption to intraocular lenses by radiolabeling and confocal laser scanning microscopy Journal of cataract and refractive surgery 2009;35(11):2000-2007 [ Show Abstract ]

Purpose: To determine albumin adsorption profiles and penetration depth of 3 intraocular lens (IOL) materials over time using confocal laser scanning microscopy (CLSM) and radiolabeling. Setting: Centre for Contact Lens Research, School of Optometry, and Department of Biology, University of Waterloo, Waterloo, Ontario, Canada. Methods: Poly(methyl methacrylate) (PMMA), silicone, and foldable hydrophilic acrylic IOLs were incubated in 0.5 mg/mL bovine serum albumin (BSA) for 1, 7, and 14 days. The BSA was conjugated with lucifer yellow VS to allow identification of the protein location by fluorescent imaging with CLSM. Next, the protein uptake was quantified using 2% 125I-labeled BSA. Results: Confocal laser scanning microscopy showed increasing BSA uptake for silicone and PMMA IOLs after 14 days of incubation (P<.05), with an apparent penetration depth of 8.7 μm ± 1.9 (SD) and 9.2 ± 1.4 μm, respectively. For hydrophilic acrylic IOLs, BSA was detected at a depth of 38 ± 7.4 μm after 1 day, followed by an increase to 192.7 ± 16.2 μm after 14 days. Despite the penetration depth into the hydrophilic acrylic IOLs, quantitative results confirmed that PMMA and hydrophilic acrylic deposited significantly less BSA (mean 278.3 ± 41.7 ng and 296.5 ± 33.1 ng, respectively) than silicone IOLs (mean 392.6 ± 37.6 ng) (P<.05). Conclusions: Silicone and PMMA IOL materials showed BSA sorption near the lens surface only, while BSA penetrated deep into the hydrophilic acrylic IOL matrix. Combining the qualitative CLSM method and quantitative radiolabeling technique provided detailed information on protein interactions with implantable biomaterials. © 2009 ASCRS and ESCRS.

Luensmann,D., Zhang,F., Subbaraman,L., Sheardown,H., Jones,L. Localization of lysozyme sorption to conventional and silicone hydrogel contact lenses using confocal microscopy Current eye research 2009;34(8):683-697 [ Show Abstract ]

PURPOSE: To investigate the distribution profile of hen egg lysozyme (HEL) through poly-2-hydroxyethyl methacrylate (pHEMA)-based lens materials and silicone hydrogel (SH) lens materials using confocal laser scanning microscopy (CLSM). METHODS: Five silicone SH materials (balafilcon A, lotrafilcon A, lotrafilcon B, galyfilcon A, senofilcon A) and four pHEMA-based materials (alphafilcon A, etafilcon A, omafilcon A, vifilcon A) were incubated in 1.9 mg/ml protein solution for 24 hours. The protein solution consisted of HEL, which was conjugated with either fluorescein isothiocyanate (FITC) or lucifer yellow VS dilithium salt (LY). CLSM (Zeiss LSM 510 META) identified the location of the fluorescently labeled protein by using 1 micro m depth scans through the lens. In a second experiment, lenses were incubated with 2% (125) I labeled HEL to determine the amount of deposited protein on each lens. Both techniques were combined to describe the individual HEL profiles. RESULTS: After the incubation in fluorescently labeled HEL, all pHEMA-based materials and the SH material balafilcon A accumulated protein throughout the entire lens material, while, for the SH lenses lotrafilcon A and lotrafilcon B, HEL was primarily detected on the lens surface alone. Differences in protein uptake pattern due solely to the two conjugated dyes were most apparent for the SH materials galyfilcon A and senofilcon A; HEL was detected throughout these lenses when conjugated with LY but accumulated primarily on the surface when conjugated with FITC. CONCLUSION: CLSM in combination with a radiolabel technique can describe both the location and degree of protein deposition on different contact lens materials.

Ngo,W., Heynen,M., Joyce,E., Jones,L. Impact of protein and lipid on neutralization times of hydrogen peroxide care regimens Eye and Contact Lens 2009;35(6):282-286 [ Show Abstract ]

Purpose: To investigate the effect of protein, lipid, and lens material on the neutralization kinetics of one-step hydrogen peroxide disinfection systems. Methods: A UV-based assay was used to determine the rate of neutralization of three one-step hydrogen peroxide systems (CIBA Vision Clear Care; CIBA Vision AOSEPT; Abbott Medical Optics UltraCare). Protein (bovine serum albumin and lysozyme) and various lipids were added to the lens cases during the neutralization phase to determine whether they influenced the rate of neutralization. Finally, rates were determined when the cases contained a silicone hydrogel lens material (lotrafilcon A) or Food and Drug Administration group IV (etafilcon A) lenses. Results: Neutralization for all three systems was complete within 90 minutes. The rate of neutralization for Clear Care and AOSEPT were not significantly different from each other (P=NS). UltraCare exhibited statistically higher levels of peroxide up to the 20-minute time point (P<0.001) Protein, lipid, or lens material did not significantly affect the rate of neutralization for any regimen (P=NS). Conclusions: Tablet-based one-step disinfection systems neutralize at a slower rate than disc-based peroxide systems, but this difference is only significant during the first 20 minutes after the onset of neutralization. Neither lens deposition nor lens material plays a role in the speed of neutralization of peroxide-based systems. © 2009 Lippincott Williams & Wilkins.

Papas,E. B., Decenzo-Verbeten,T., Fonn,D., Holden,B. A., Kollbaum,P. S., Situ,P., Tan,J., Woods,C. Utility of short-term evaluation of presbyopic contact lens performance Eye and Contact Lens 2009;35(3):144-148 [ Show Abstract ]

OBJECTIVES: To establish if evaluations of multifocal contact lens performance conducted at dispensing are representative of behavior after a moderate adaptation period. METHODS: Eighty-eight presbyopic subjects, across four clinical sites, wore each of four multifocal soft contact lenses (ACUVUE BIFOCAL, Focus Progressives, Proclear Multifocal, and SofLens Multifocal) for 4 days of daily wear. Comprehensive performance assessments were conducted at dispensing and after 4 days wear and included the following objective metrics: LogMAR acuity (contrast, 90% and 10%; illumination, 250 and 10 cd/m; distance, 6 m, 100 cm, and 40 cm), stereopsis (RANDOT), reading critical print size and maximum speed and range of clear vision at near. Subjective assessments were made, with 100-point numerical rating scales, of comfort, ghosting (distance, near), visual quality (distance, intermediate, and near), and the appearance of haloes. At two sites, subjects (n = 39) also rated visual fluctuation (distance, intermediate, and near), facial recognition, and overall satisfaction. RESULTS: Among the objective variables, significant differences (paired t test, P<0.05) between dispensing and 4 days were found only for range of clear vision at near (2.9 ± 2.0 cm; mean difference ± standard deviation) and high contrast near acuity in low illumination (-0.013 ± 0.011 LogMAR). With the exception of insertion comfort, all subjective variables showed significant decrements over the same period. Overall satisfaction declined by an average of 10.9 ± 5.1 points. CONCLUSIONS: Early assessment is relatively unrepresentative of performance later on during multifocal contact lens wear. Acuity based measures of vision remain substantially unchanged over the medium term, apparently because these metrics are insensitive indicators of performance compared with subjective alternatives. © 2009 Lippincott Williams & Wilkins.

Schulze,M. M., Hutchings,N., Simpson,T. L. The perceived bulbar redness of clinical grading scales Optometry and Vision Science 2009;86(11):E1250-E1258 [ Show Abstract ]

Purpose. To use a psychophysical scaling method to estimate the perceived redness of reference images of the McMonnies and Chapman-Davies (six reference levels), Institute for Eye Research (four), Efron (five), and Validated Bulbar Redness (five) bulbar redness grading scales. Methods. Regions of interest were cropped out of the grading scale reference images; three separate image sets (color, grayscale, and binarized) were created for each scale, combining to a total of 20 images per image set. Ten naïve observers were asked to arrange printed copies of the 20 images per image set across a distance of 1.5 m on a flat surface, so that separation reflected their perception of bulbar redness; only start and end point of this range were indicated. The position of each image was averaged across observers to represent the perceived redness for this image, within the 0 to 100 range. Subjective data were compared with physical attributes (chromaticity and spatial metrics) of redness. Results. For each image set, perceived redness of the reference images within each scale was ordered as expected, but not all consecutive within-scale levels were rated as having different redness. Perceived redness of the reference images varied between scales, with different ranges of severity being covered by the images. Perception of redness severity depended on the image set (repeated-measures analysis of variance; all p ≤ 0.0002). The perceived redness was strongly associated with the physical attributes of the reference images. Conclusions. Subjective estimates of redness are based on a combination of chromaticity and vessel-based components. Psychophysical scaling of perceived redness lends itself to being used to cross-calibrate these four clinical scales. © 2009 American Academy of Optometry.

Sorbara,L., Jones,L., Williams-Lyn,D. Contact lens induced papillary conjunctivitis with silicone hydrogel lenses Contact Lens and Anterior Eye 2009;32(2):93-96 [ Show Abstract ]

PURPOSE: To describe the refitting of a soft lens wearer into a silicone hydrogel lens due to neovascularization. This change, in turn, caused contact lens induced papillary conjunctivitis (CLPC) and a further refitting was necessary. METHODS: The patient was refit into a high Dk surface treated silicone hydrogel with a high modulus value. A second refitting was undertaken into a lower Dk silicone hydrogel contact lens with a lower modulus value which had no surface treatment but incorporated an internal wetting agent. RESULTS: A high Dk/t lens was used to resolve existing neovascularization and chronic hyperaemia. Subsequently, CLPC response occurred, possibly due to a combination of factors, resulting in irritation of the palpebral conjunctiva. This resulted in temporary lens discontinuation. A second silicone hydrogel lens was fit, along with the use of a non-preserved care system, which led to improvement and eventual resolution of the condition. CONCLUSION: High Dk silicone hydrogel lenses have shown excellent efficacy in resolving hypoxic complications such as neovascularization and hyperaemia. However, attention needs to be paid to their potential effect on the upper tarsal plate. More than one silicone hydrogel lens may be needed to help resolve these issues.

Sorbara,L., Peterson,R., Woods,C., Fonn,D. Multipurpose disinfecting solutions and their interactions with a silicone hydrogel lens Eye and Contact Lens 2009;35(2):92-97 [ Show Abstract ]

PURPOSE:: To assess the compatibility of a new silicone hydrogel lens, asmofilcon A (with four multipurpose disinfecting solutions: OPTIFREE RepleniSH, ReNu MultiPlus, Solo-Care Aqua and MeniCare Soft). Ocular responses and subjective responses were monitored with each lens-care system combination. METHODS:: The study was conducted as a prospective, bilateral, clinical trial with a single-masked investigator, and randomized cross-over design with four phases, (one for each care system). Each study phase comprised of two consecutive days of lens wear where the lenses were inserted on day 1 directly from the blister-packs and worn for over 8 hr, then inserted on day 2 after overnight disinfection with one of the study lens care systems. Twenty-five adapted soft contact lens wearers who were able to wear their habitual lenses comfortably for more than 12 hr were recruited. RESULTS:: There were statistically significant differences in corneal staining found for all the lens-care systems when comparing the results of day 1 (from the blister pack) with day 2 (following care system use) (P < 0.05). ReNu MultiPlus solution had the highest grade for corneal staining at the 2-hr time point on day 2 which then decreased by 6 hr (P < 0.05). There was no difference between the lens care systems and the rating of subjective comfort over either of the two days. The rating of dryness and burning sensations were only slightly increased at 6 hr for all lens care systems except ReNu MultiPlus where burning was highest on insertion (P < 0.05). CONCLUSION:: Corneal staining observed in this study does not seem to have been related to the presence of polyhexamethylene biguanide (0.0001% wv) that was present in three of the four care systems. Only one care system (ReNu MultiPlus) demonstrated an associated level of corneal staining that was statistically significant; however, this was not considered to be of clinical relevance. These results suggest that using this novel surface-treated silicone hydrogel lens may result in less lens and lens care-related interactions. © 2009 Lippincott Williams & Wilkins.

Subbaraman,L. N., Glasier,M. A., Sheardown,H., Jones,L. Efficacy of an extraction solvent used to quantify albumin deposition on hydrogel contact lens materials Eye and Contact Lens 2009;35(2):76-80 [ Show Abstract ]

OBJECTIVES: Extracting proteins from conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials using a mixture of trifluoroacetic acid/acetonitrile (TFA/ACN) is a well-established procedure for quantifying individual and total protein deposited on contact lenses. The purpose of this study was to determine the efficacy of TFA/ACN in extracting albumin from SH and a CH group IV lens material using an in vitro model. METHODS: One CH group IV lens material (etafilcon A) and five different SH lens materials (lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A, and senofilcon A) were incubated in both simple albumin solution and a complex artificial tear protein solution containing 125I-labeled albumin. All the lens materials were incubated for 14 days at 37 degrees C with constant rotations. Following the incubation period, radioactive counts were determined and the lenses were placed in an appropriate volume of the extraction solvent. After the specified time, the lenses were removed and radioactive counts were determined again to calculate the amount of albumin remaining on the lenses post-extraction. RESULTS: Extraction efficiencies for albumin from the artificial tear protein solution were 97.2% +/- 2 for etafilcon A, 77.3% +/- 6.2 for lotrafilcon A, 73.5% +/- 5.6 for lotrafilcon B, 81.5% +/- 5.8 for balafilcon, 91.2% +/- 3.4 for galyfilcon A, and 89.2% +/- 3.4 for senofilcon A. Results were similar for the albumin extracted after incubating in the simple albumin solution. CONCLUSIONS: Although TFA/ACN is efficient at extracting albumin deposited on etafilcon lenses, it does not extract all the albumin that is deposited on SH lenses and alternative extraction procedures should be sought.

Subbaraman,L. N., Woods,J., Teichroeb,J. H., Jones,L. Protein deposition on a lathe-cut silicone hydrogel contact lens material Optometry and Vision Science 2009;86(3):244-250 [ Show Abstract ]

PURPOSE: To determine the quantity of total protein, total lysozyme, and the conformational state of lysozyme deposited on a novel, lathe-cut silicone hydrogel (SiHy) contact lens material (sifilcon A) after 3 months of wear. METHODS: Twenty-four subjects completed a prospective, bilateral, daily-wear, 9-month clinical evaluation in which the subjects were fitted with a novel, custom-made, lathe-cut SiHy lens material. The lenses were worn for three consecutive 3-month periods, with lenses being replaced after each period of wear. After 3 months of wear, the lenses from the left eye were collected and assessed for protein analysis. The total protein deposited on the lenses was determined by a modified Bradford assay, total lysozyme using Western blotting and the lysozyme activity was determined using a modified micrococcal assay. RESULTS: The total protein recovered from the custom-made lenses was 5.3 +/- 2.3 microg/lens and the total lysozyme was 2.4 +/- 1.2 microg/lens. The denatured lysozyme found on the lenses was 1.9 +/- 1.0 microg/lens and the percentage of lysozyme denatured was 80 +/- 10%. CONCLUSIONS: Even after 3 months of wear, the quantity of protein and the conformational state of lysozyme deposited on these novel lens materials was very similar to that found on similar surface-coated SiHy lenses after 2 to 4 weeks of wear. These results indicate that extended use of the sifilcon A material is not deleterious in terms of the quantity and quality of protein deposited on the lens.

Varikooty,J., Simpson,T. L. The interblink interval I: The relationship between sensation intensity and tear film disruption Investigative Ophthalmology and Visual Science 2009;50(3):1087-1092 [ Show Abstract ]

PURPOSE. To find the relationship between tear film drying and sensation during the interblink period. METHODS. One eye was taped shut, and after a blink the subjects were required to keep the other eye open. Digital video images of the ocular surface (with fluorescein) were obtained using a slit lamp biomicroscope while 23 subjects rated the intensity of the ocular surface sensation by adjusting a one-turn potentiometer to represent the strength of the sensation. They were trained to use the potentiometer before the data were collected. In addition, the characteristics of the sensation as spoken by the subject were recorded. RESULTS. The sensation was generally triphasic, with initial constant sensation and a subsequent biphasic period, with intensity increasing slowly followed by a rapid increase before the subjects blinked (correlations were all r > 0.95). Tear film drying dynamics were also biphasic, and drying and sensation were strongly associated, with a correlation of 0.94 between the break in the bilinear functions of sensation and drying. CONCLUSIONS. The method provides novel information about the development of ocular sensation during ocular surface drying. As evidenced by the complex functions required to adequately describe the relationships, tear film drying and ocular surface sensations are associated in complex ways. © Association for Research in Vision and Ophthalmology.

Woods,C. A., Cumming,B. The impact of test medium on use of visual analogue scales Eye and Contact Lens 2009;35(1):6-10 [ Show Abstract ]

OBJECTIVES: Visual analog scales are frequently used as a means of allowing participants to rate symptoms during clinical trials. The accuracy and reproducibility of these scales play an important role in determining the experimental value of the data they provide. This study was initiated to compare the data collected using paper- and computer-based (Tablet PC) analog scales to better understand the variability in data provided by a visual analog scale. METHODS: Thirty participants rated ocular comfort, redness, and clarity of vision (right and left eyes) on a nondemarcated horizontal line on both paper and a Tablet PC. Measurements were taken in the morning between the hours of 8:30 and 10:30 am and again the same day between 2:30 and 4:30 pm. RESULTS: The mean difference between the measures recorded in the morning for the 2 media was 2.6 ± 0.9 (confidence intervals, 2 standard errors of the differences) units on a 100 unit scale, with the Tablet PC having the higher mean measure. The limits of agreement (2 standard deviations of the differences) was 9.4 units. Comparing the difference of the differences (1.0 ± 1.3) between the 2 methods of measure (morning vs. afternoon) the visual analog scales on the Tablet PC seemed to have good reproducibility of agreement in comparison with the paper version. CONCLUSIONS: Discrepancy analysis yielded no significant difference and slight bias between paper- and computer-based analog scales. Repeatability of measures using the Tablet PC was also demonstrated. These results suggest that the choice of medium does not significantly influence the outcome for subjective analog scales. © 2009 Lippincott Williams & Wilkins, Inc.

Woods,J., Woods,C. A., Fonn,D. Early symptomatic presbyopes-What correction modality works best? Eye and Contact Lens 2009;35(5):221-226 [ Show Abstract ]

Purpose: To compare the performance of a low-addition silicone hydrogel multifocal soft lens with other soft lens correction options in a group of habitual soft lens wearers of distance correction who are symptomatic of early presbyopia. METHOD: This clinical study was designed as a prospective, double-masked, randomized, crossover, dispensing trial consisting of four 1-week phases, one for each of the correction modalities: a low-addition silicone hydrogel multifocal soft lens, monovision, habitual correction, and optimized distance visual correction. The prescriptions of all modalities were finalized at a single fitting visit, and the lenses were worn according to a randomized schedule. All lenses were made from lotrafilcon B material. A series of objective vision tests were conducted: high- and low-contrast LogMAR under high- and low-room lighting conditions, stereopsis, and critical print size. A number of other data collection methods used were novel: some data were collected under controlled laboratory-based conditions and others under "real-world" conditions, some of which were completed on a BlackBerry hand-held communication device. RESULTS: All participants were able to be fit with all four correction modalities. Objective vision tests showed no statistical difference between the lens modalities except in the case of low-contrast near LogMAR acuity under low-lighting levels where monovision (+0.29 ± 0.10) performed better than the multifocal (+0.33 ± 0.11, P=0.027) and the habitual (+0.37 ± 0.12, P<0.001) modalities. Subjective ratings indicated a statistically better performance provided by the multifocal correction compared with monovision, particularly for the vision associated with driving tasks such as driving during the daytime (93.3 ± 8.8 vs. 84.2 ± 23.7, P=0.05), at nighttime (88.8 ± 11.7 vs. 74.9 ± 23.6, P=0.001), any associated haloes or glare (92.0 ± 10.6 vs. 78.0 ± 22.8, P=0.003), and observing road signs (90.1 ± 11.8 vs. 79.4 ± 20.2, P=0.027). Preference for the multifocal compared with monovision was also reported when watching television (95.0 ± 6.4 vs. 82.6 ± 20.1, P=0.001) and when changing focus from distance to near (87.0 ± 13.4 vs. 66.1 ± 32.2, P<0.001). CONCLUSIONS: For this group of early presbyopes, the AIR OPTIX AQUA MULTIFOCAL-Low Add provided a successful option for visual correction, which was supported by the results of subjective ratings, many of which were made during or immediately after performing such activities as reading, using a computer, watching television, and driving. These results suggest that making a prediction of "success or not" based on consulting room acuity tests alone is probably unwise. Copyright © Contact Lens Association of Ophthalmologists, Inc.

Young,G., Keir,N., Hunt,C., Woods,C. A. Clinical evaluation of long-term users of two contact lens care preservative systems Eye and Contact Lens 2009;35(2):50-58 [ Show Abstract ]

PURPOSE: To clinically evaluate long-term users of two different contact lens care preservative systems and to investigate whether prolonged use is associated with an increase in the prevalence of dry eye. METHODS: Eighty-nine wearers of group IV hydrogel or silicone hydrogel lenses participated in this one-visit, investigator-masked study. Subjects were required to have consistently used a polyhexamethylene biguanide (PHMB) or polyquaternium-1 (PQT) based solution for 2 years. Consistent use was defined as 80% for the past 2 years and 100% for the past year. Clinical assessments included: average and comfortable wear time; overall and end-of-day comfort; signs of dryness, discomfort, burning or stinging, grittiness or scratchiness and visual changes; non-invasive and fluorescein break-up-time; pre-ocular tear film lipids, tear meniscus height, Schirmer and fluorescein clearance tests; limbal and bulbar hyperemia; palpebral roughness; corneal and conjunctival staining; lens front surface wetting; and lens film deposits. RESULTS: Significantly more grittiness or scratchiness was reported by subjects using a PHMB-containing system (67% vs. 44%; P = 0.02). Palpebral roughness and hyperemia were significantly greater in the PHMB group wearing group IV lenses (P = 0.01 and P = 0.05, respectively). Corneal staining was significantly higher in the PHMB users in all four peripheral sectors (P < 0.01). Nasal and temporal conjunctival staining was also significantly higher for users of PHMB-containing systems (P < 0.05). Front surface lens wettability was significantly better for group IV PQT users compared to PHMB users (P = 0.008), with 84% vs. 72%, respectively, with lenses graded by the investigator as having "good" or "excellent" wettability. Significantly higher levels of lens front surface film deposits were noted with PHMB users (P = 0.007), with 58% of group IV lenses treated with PHMB compared with 38% of group IV lenses treated with PQT showing some lens front surface film deposition. No significant differences between the two preservative system groups were noted for the range of dry eye evaluations nor the remaining clinical assessments. CONCLUSIONS: Differences in both ocular and lens characteristic were observed between long-term users of two preservative systems used in many contact lens multi-purpose solutions. The findings from this study did not support the hypothesis that prolonged use of PHMB-containing solutions leads to dry eye. Additional studies including a larger sample size and perhaps longer use of the systems could help to further elucidate differences in clinical performance between systems.

2008

Bitton,E., Keech,A., Jones,L., Simpson,T. Subjective and objective variation of the tear film pre- and post-sleep Optometry and Vision Science 2008;85(8):740-749 [ Show Abstract ]

PURPOSE: To date, few studies have correlated the overnight effects of the preocular tear film (POTF) with subjective symptoms. This study investigates the POTF volume and stability, bulbar hyperemia (BH), tear ferning (TF) and the participant's subjective symptoms, pre- and post-sleep. METHODS: Thirty subjects were recruited, consisting of two evenly distributed groups who were symptomatic of dry eye (DE) and those that were asymptomatic dry eye, determined using the McMonnies questionnaire. Subjects were evaluated at 10 p.m. (baseline), on waking at 7 a.m., and then hourly until 10 a.m. At each visit, tear meniscus height (TMH), various subjective factors, BH and POTF stability by non-invasive break-up time (NIBUT) were assessed. Tear collection was performed at 10 p.m, 7 and 10 a.m. for TF analysis. RESULTS: With the exception of burning, all other symptoms (comfort, dryness, clarity of vision, and grittiness) revealed an overnight change (p < 0.05) within each group, but not between the two groups (p > 0.05). Both the tear meniscus height and BH were elevated upon waking and differed significantly between test times for each group (p < 0.05), but not between groups (p > 0.05). NIBUT was lower for the DE group (p < 0.001). The non-dry eye (NDE) group did not significantly alter over time (p > 0.05), but the DE group did (p = 0.004), with a longer NIBUT in the morning. TF demonstrated a degraded pattern upon waking for both groups (p < 0.05). Most of the changes returned to baseline within an hour after waking. CONCLUSIONS: The properties of the POTF undergo a change during extended periods of eye closure and the human POTF is different upon waking to that present immediately before sleep. Most of the parameters determined rapidly revert to baseline levels once the POTF is allowed to refresh.

Caffery,B., Joyce,E., Boone,A., Slomovic,A., Simpson,T., Jones,L., Senchyna,M. Tear lipocalin and lysozyme in sjögren and non-sjogren dry eye Optometry and Vision Science 2008;85(8):661-667 [ Show Abstract ]

PURPOSE.: To evaluate the concentration of tear lipocalin, lysozyme, and total protein in Sjogrens Syndrome (SS), non-Sjogrens keratoconjunctivitis sicca (KCS), and non-dry-eyed (NDE) individuals. METHODS.: Seventy-six subjects were recruited for this study: 25 SS subjects; 25 KCS subjects, and 26 NDE individuals. Symptoms were measured with a visual analogue scale. Tear flow was measured by the Schirmer I test without anesthesia. Tears were collected using an eye wash technique. Total tear protein was quantified using the DC Protein Assay Kit. Tear lipocalin and lysozyme were quantified via Western blotting performed on a Phast System. RESULTS.: By definition, the SS and KCS groups both had significantly lower mean Schirmer scores (5.12 ± 5.96 mm and 7.84 ± 7.35 mm) compared with the NDE group (23.83 ± 7.85 mm; p < 0.0001). There was no difference in mean Schirmer scores between SS and KCS groups (p = 0.19). The tear film of the SS group was characterized by significantly reduced (p < 0.0001) total protein and lipocalin concentrations compared with both KCS and NDE groups. No difference between the KCS and NDE groups was found in total protein (p = 0.92) or lipocalin (p = 0.19) concentration. In contrast, the concentration of tear film lysozyme was found to be statistically similar in all three groups examined. No statistically significant correlation was found in any group between mean Schirmer values compared with total protein, lipocalin or lysozyme concentration. CONCLUSION.: Our data demonstrate a biochemical distinction between the Sjogrens group compared with both KCS and control groups, in that both tear lipocalin and total tear protein were significantly reduced. Although correlations were not found between protein measurements and tear flow, a combination of tests including Schirmer I and quantitation of tear film biomarkers may allow for the identification of SS patients without the need for invasive testing. © 2008 American Academy of Optometry.

Dalton,K., Subbaraman,L. N., Rogers,R., Jones,L. Physical properties of soft contact lens solutions Optometry and Vision Science 2008;85(2):122-128 [ Show Abstract ]

Purpose. To investigate the physical properties of commercially available soft contact lens solutions.
Methods. The pH, osmolality, surface tension (ST), and viscosity of various soft contact lens solutions were measured at room temperature. Viscosity measurements were also taken at 34°C. The solutions examined were Opti-Free Express (OFX), Opti-Free RepleniSH (OFR), Complete Moisture Plus (COM), UltraCare (UC), ReNu MultiPlus, Sensitive Eyes, AOSept (AO), Clear Care, SoloCare Aqua, and SoftWear saline. The peroxide solutions were measured before and after neutralization.
Results. The pH of most solutions was close to neutral (range 7.00-7.36), except for OFX and neutralized AO and Clear Care. The osmolality values of most solutions were in the 275 to 310 mOsm/kg range. OFX exhibited a significantly lower osmolality (225 mOsm/kg; p < 0.001), whereas UC was significantly higher (329 mOsm/kg; p < 0.001). Neutralized AO and SoftWear saline had ST values of approximately 67 mN/m. OFX, OFR, and SoloCare Aqua exhibited low ST values in the 30 to 35 mN/m range. The remaining solutions exhibited intermediate ST values of approximately 40 mN/m. These three groupings were significantly different (p < 0.001). The average viscosity of most solutions at room temperature was between 0.95 and 1.26 cP, except for COM (3.02 cP; p < 0.001). At 34°C, the average viscosity of most solutions was between 0.70 and 0.83 cP, except for COM, which had a viscosity of 1.92 cP (p < 0.001). The un-neutralized peroxide solutions had very different pH and osmolality values from all the solutions that would directly contact the eye (p < 0.001). Their viscosity and ST values were similar (p = NS).
Conclusions. This study detailed many physical properties of soft lens solutions that are not readily available and indicated that certain properties vary significantly among these products.

Dumbleton,K. A., Woods,C. A., Jones,L. W., Fonn,D. Comfort and adaptation to silicone hydrogel lenses for daily wear Eye and Contact Lens 2008;34(4):215-223 [ Show Abstract ]

Objectives. To investigate initial comfort and adaptation of currently successful low oxygen transmissibility soft lens wearers refitted with silicone hydrogel (SH) lenses for daily wear. Methods. Fifty-five subjects were enrolled in a subject-masked 5-month clinical trial in which they wore 5 SH lenses in a randomized, crossover design. Comfort, burning, and dryness were rated on scales of 0 to 100 immediately on insertion and the time for lens settling was recorded. Symptoms were then rated at various times, using BlackBerry wireless communication devices (Research in Motion, Waterloo, Canada), during the day for 2 cycles of 2 weeks wear for each lens type. Results. Comfort immediately on insertion varied between lens types (P=0.002). All lens types were reported by the subjects to have settled within 30 to 45 sec of insertion (P=0.14) and "settled" comfort was greater than comfort immediately on insertion (P<0.001). Comfort within the first hour of wear also varied between lens types (P=0.02). Comfort during the day decreased significantly for all lenses (P=0.001), but there was no difference between lenses (P=0.19) and no effect of lens age (P=0.15). The wearing times were greater with the SH lenses than the habitual lenses worn before study commencement (P=0.001). Overall performance of the lenses after 4 weeks was high, with no difference between lenses (P=0.45). Conclusions. Initial comfort and adaptation to all SH lenses were good and no differences in the overall ratings were found between the 5 SH lenses investigated. Decreased comfort was noted later in the day with all lens types, but longer wearing times were reported with the SH lenses than previous hydroxyethyl methacrylate-based lenses. © 2008 Contact Lens Association of Ophthalmologists, Inc.

Glasier,M. -A, Keech,A., Sheardown,H., Subbaraman,L. N., Jones,L. Conformational and quantitative characterization of lysozyme extracted from galyfilcon and senofilcon silicone hydrogel contact lenses Current eye research 2008;33(1):1-11 [ Show Abstract ]

PURPOSE: To compare two solvents for retrieval of lysozyme deposited on a silicone hydrogel (SH) contact lens material galyfilcon A (GA; Acuvue Advance). METHODS: Two buffers used were 50:50 acetonitrile/0.02% trifluoroacetic acid (buffer 1) and 50:50 acetonitrile/50 mM NaOH (buffer 2). RESULTS: Extraction efficiency from GA lenses was 74% (buffer 1) and 83% (buffer 2). Buffer 2 decreased lysozyme activity > buffer 1. Ex vivo GA lenses showed total protein deposition of 2-16 microg/lens with total lysozyme deposition of 0.3-3.9 microg/lens. CONCLUSIONS: We have developed a low acid strength extraction buffer that can be used to efficiently extract active lysozyme protein from novel siloxane-based contact lens materials.

Glasier,M. -A, Subbaraman,L. N., Senchyna,M., Jones,L. A solid-phase assay for the quantitation of total protein eluted from balafilcon, lotrafilcon, and etafilcon contact lenses Current eye research 2008;33(8):631-640 [ Show Abstract ]

PURPOSE: To compare two variations of a membrane-based protein assay utilizing Amido black (AB) detection with a commercially available 3-(4-carboxybenzoyl) quinoline-2-carboxaldehyde (CBQCA) assay for use in the quantitation of individual tear proteins, pooled human tear proteins, and protein extracted from ex vivo lotrafilcon A, balafilcon A, and etafilcon A contact lens materials. METHODS: Ex vivo contact lens extracts, pooled human tears, and individual tear proteins (human serum albumin (HSA), bovine lactoferrin, human secretory immunoglobulin A (sIgA), human lysozyme) were subjected to three solid-phase assays: AB on polyvinylidene difluoride (AB on PVDF) and AB on nitrocellulose (AB on NC) and the CBQCA assay. Micro-bicinchonic acid (micro-BCA) assay was also employed with lens extracts to determine total protein concentration. Individual and pooled tear proteins were referenced to a micro version of the quantitative ninhydrin protein assay. RESULTS: The CBQCA demonstrated the greatest overall sensitivity and lowest intra- and inter-assay variability. AB on NC demonstrated the most accurate ability to quantify total protein in pooled human tear samples, although it also displayed the greatest protein-to-protein variation using individual tear proteins. The CBQCA assay displayed the greatest cross-reactivity with unworn balafilcon and lotrafilcon lens extracts, whereas AB on NC demonstrated the least. AB on NC measured similar amounts of total protein in extracted ex vivo lenses as the CBQCA assay if background interference was subtracted from CBQCA values. AB on PVDF measured the lowest amount of deposited protein from ex vivo lenses. CONCLUSION: Both the AB on NC and CBQCA assays can be used to measure protein in extracts of lotrafilcon, balafilcon, and etafilcon lens materials.

Haque,S., Fonn,D., Simpson,T., Jones,L. Epithelial thickness changes from the induction of myopia with CRTH RGP contact lenses Investigative Ophthalmology and Visual Science 2008;49(8):3345-3350 [ Show Abstract ]

PURPOSE. To investigate changes in epithelial thickness after overnight wear of CRTH rigid gas-permeable (RGP) lenses (Paragon Vision Sciences, Mesa, AZ) for the correction of hyperopia. METHODS. Twenty subjects wore a +3.50 D hyperopia-correcting CRTH lens on one eye for a single night in an attempt to induce myopia (first study). The untreated eye served as the control. Corneal and epithelial thickness was measured at nine points across the horizontal meridian by OCT. Measurements were obtained the night before lens wear, immediately after lens removal the next morning, and 1, 3, 6, and 12 hours after removal. Measurements were obtained 28 hours later, to observe recovery. Then, the attempted hyperopic corrections of +1.50 and +3.50 D were evaluated, using CRTH lenses in both eyes of 20 subjects for a single night (second study). RESULTS. All values were compared to baseline unless otherwise stated. In the first study, the treated eye's central and midperipheral epithelial thickness increased by 21.5% ± 8.6% and 13.3% ± 7.6%, respectively, after lens removal (P < 0.001). The control eye's central epithelial thickness (CET) increased by 7.1% ± 6.0% (P < 0.05). In the second study, CET increased by 17.6% ± 8.5% (P < 0.001) in the +3.50 D-treated eye and by 13.3% ± 4.8% (P < 0.001) in the +1.50 D-treated eye. Midperipheral epithelial thickening was 5.9% ± 4.7% (P < 0.05) in the +3.50 D-treated eye and 6.0% ± 6.3% (P < 0.05) in the +1.50 D-treated eye. CONCLUSIONS. CRTH lenses, designed to correct hyperopia, when worn overnight, caused an increase in CET. The amount of epithelial change seemed to differ with modified lens design. Copyright © Association for Research in Vision and Ophthalmology.

Hui,A., Boone,A., Jones,L. Uptake and release of ciprofloxacin-HCl from conventional and silicone hydrogel contact lens materials. Eye & contact lens 2008;34(5):266-271 [ Show Abstract ]

OBJECTIVES: To investigate the uptake and release characteristics of the antibiotic ciprofloxacin-HCl in conventional and silicone hydrogel lenses, and evaluate their potential as therapeutic drug delivery devices. METHODS: Nine differing soft contact lens materials were soaked in a 0.3% ciprofloxacin-HCl solution at 34 degrees C. The uptake of the drug into the lenses was measured by the change in concentration over 24 hours using fluorescence spectrophotometry. The lenses were then placed in a buffered saline solution, and the release of the drug from the lenses was also measured using spectrophotometry. RESULTS: The release of drug varied from 0.016 +/- 0.004 mg/lens for lotrafilcon A lenses to 0.42 +/- 0.03 mg/lens for etafilcon A lenses, with an average of 0.133 mg/lens. The 3 conventional lenses used in the study released a statistically significantly different amount of drug when compared with the silicone hydrogels. The release of drug was very rapid, with drug release reaching a plateau after no more than 10 minutes for the majority of the lenses. The majority of the lenses were able to release enough drug to achieve minimum inhibitory concentration 90 for most resistant ocular pathogens. Ciprofloxacin was found to heavily precipitate on the etafilcon A lenses during the release phase at physiologic pH. CONCLUSION: While balafilcon A released the most drug from the silicone hydrogel materials, all materials released the drug too quickly to be effective as drug delivery devices.

Lu,F., Simpson,T., Sorbara,L., Fonn,D. Malleability of the ocular surface in response to mechanical stress induced by orthokeratology contact lenses Cornea 2008;27(2):133-141 [ Show Abstract ]

PURPOSE: To determine the malleability of the ocular surface by examining the acute effects of local mechanical stress on optical performance, corneal shape, and corneal/epithelial thickness after corneal refractive therapy for myopia and hyperopia (CRT and CRTH). METHODS: Twenty ametropes (spherical equivalent: -2.08 ± 2.31 D) wore CRT and CRTH lenses in a random order on 1 eye (randomly selected). The lenses were worn for 15, 30, and 60 minutes (randomly ordered, with each period taking place on a different day). Refractive error, aberrations, corneal topography, and corneal/epithelial thickness (using OCT) were measured before and after lens wear. The measurements were performed on the control eyes at the 60-minute visit only. RESULTS: With both CRT and CRTH lens wear, significant changes occurred in many parameters from the 15-minute time point. The refractive error and defocus decreased after CRT lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P 0.05). CONCLUSIONS: CRT lenses for myopia and hyperopia induce significant structural and optical changes in as little as 15 minutes. The cornea, particularly the epithelium, is remarkably malleable, with rapid steepening and flattening possible in little time. © 2008 Lippincott Williams & Wilkins, Inc.

Luensmann,D., Jones,L. Albumin adsorption to contact lens materials: A review Contact Lens and Anterior Eye 2008;31(4):179-187 [ Show Abstract ]

During contact lens wear, tear film components such as lipids, mucins and proteins tend to deposit on and within the lens material and may cause discomfort, reduced vision and inflammatory reactions. The tear film protein that has attracted most interest when studying contact lens deposition is the small (14 kDa), positively charged protein lysozyme. Albumin, which is a much larger protein (66 kDa) with an overall net negative charge is also of interest, and shows very different adsorption patterns to lysozyme. The concentration of albumin in the tear film is relatively low compared to the concentration in blood serum, but this value increases markedly under various conditions, including when the eye is closed, during contact lens wear and in various dry eye states. Gaining an understanding of the manner in which albumin deposits on biomaterials is of importance for contact lens wear, as well as for other medical applications where HEMA-based materials are used for implants, artificial blood vessels or drug delivery devices. This review paper summarizes the impact of individual material compositions, water content, hydrophobicity and electrostatic attraction on the adsorption behavior of the protein albumin.

Schulze,M. M., Hutchings,N., Simpson,T. L. The use of fractal analysis and photometry to estimate the accuracy of bulbar redness grading scales Investigative Ophthalmology and Visual Science 2008;49(4):1398-1406 [ Show Abstract ]

Purpose. To use physical attributes of redness to determine the accuracy of four bulbar redness grading scales, and to cross- calibrate the scales based on these physical measures. Methods. Two image-processing metrics, fractal dimension (D) and percentage of pixel coverage (% PC), as well as photometric chromaticity were selected as physical measures, to describe and compare grades of bulbar redness among the McMonnies/Chapman-Davies scale, the Efron Scale, the Institute for Eye Research scale, and a validated scale developed at the Centre for Contact Lens Research. Two sets of images were prepared by using image processing: The first included multiple segments covering the largest possible region of interest (ROI) within the bulbar conjunctiva in the original images; the second contained modified scale images that were matched in size and resolution across scales, and a single, equally-sized ROI. To measure photometric chromaticity, the original scale images were displayed on a computer monitor, and multiple conjunctival segments were analyzed. Pearson correlation coefficients between each set of image metrics and the reference image grades were calculated to determine the accuracy of the scales. Results. Correlations were high between reference image grades and all sets of objective metrics (all Pearson's r ≥ 0.88, P ≤ 0.05); each physical attribute pointed to a different scale as being most accurate. Independent of the physical attribute used, there were wide discrepancies between scale grades, with almost no overlap when cross-calibrating and comparing the scales. Conclusions. Despite the generally strong linear associations between the physical characteristics of reference images in each scale, the scales themselves are not inherently accurate and are too different to allow for cross-calibration. Copyright © Association for Research in Vision and Ophthalmology.

Simpson,T. L., Situ,P., Jones,L. W., Fonn,D. Dry eye symptoms assessed by four questionnaires Optometry and Vision Science 2008;85(8):E692-E699 [ Show Abstract ]

PURPOSE.: To establish the relationships between commonly used questionnaires including Dry Eye Questionnaire, McMonnies Questionnaire, and Ocular Surface Disease Index, and to test the construct and face validity of the simple Subjective Evaluation of Symptom of Dryness. METHODS.: Ninety-seven non-contact lens wearing subjects were enrolled in the study and classified into either a "dry" and "non-dry" group using a single score from an initially applied subjective evaluation of symptom of dryness. The four questionnaires were then completed in a random order. The unidimensionality and accuracy of the responses was assessed using Rasch and receiver (or relative) operating characteristics curve analysis and the characteristics of and association between symptoms were compared using non-parametric statistics. RESULTS.: The responses from the Dry Eye Questionnaire, McMonnies Questionnaire, and Ocular Surface Disease Index met the Rasch analysis criterion of unidimensionality. Each test separated the symptomatic and asymptomatic groups well [all receiver (or relative) operating characteristics area-under-the-curve statistics at least 0.88] and there were significant associations between the results from each questionnaire (all Spearman ρ at least 0.64). CONCLUSIONS.: The results illustrate that different questionnaire-based instruments examining symptoms in controls and symptomatic subjects derive unidimensional data that are similar inasmuch as the overall scores are highly correlated. The data also point to the utility of a quick, three-question screening tool in dry eye research. © 2008 American Academy of Optometry.

Simpson,T., Fonn,D. Optical coherence tomography of the anterior segment Ocular Surface 2008;6(3):117-127 [ Show Abstract ]

Perhaps no diagnostic technology has emerged as rapidly in ophthalmology as optical coherence tomography (OCT). A single clinical device for this noninvasive imaging technique was first released in 1996, and now at least ten clinical devices are available. Although the first clinical anterior segment OCT was marketed only 2 years ago, a substantial amount of work has been done using modified retinal imagers or prototype laboratory-based imagers. In this review, we discuss OCT imaging primarily of the cornea. We also highlight previous and current publications on nonclinical and clinical uses of the device to illustrate how anterior segment OCT can be used to understand corneal structure and function in health and disease. © 2008 Ethis Communications, Inc.

Situ,P., Simpson,T. L., Fonn,D., Jones,L. W. Conjunctival and corneal pneumatic sensitivity is associated with signs and symptoms of ocular dryness Investigative Ophthalmology and Visual Science 2008;49(7):2971-2976 [ Show Abstract ]

PURPOSE: To investigate the relationships of dry eye symptoms and corneal and conjunctival sensitivity to pneumatic stimulation, tear film stability, and clinical ocular surface characteristics in symptomatic and asymptomatic subjects. METHODS: Ninety-seven subjects were enrolled and grouped by a questionnaire-based single score for symptoms of ocular dryness (none to trace, non-dry group; mild to severe, symptomatic group); 43 were symptomatic and 54 were non-dry. Corneal (K) and conjunctival (C) sensitivities were measured with a computer-controlled Belmonte pneumatic (room temperature) stimulus. Symptoms were assessed according to the Ocular Surface Disease Index (OSDI). Ocular surface staining with fluorescein (FL) and lissamine green (LG), noninvasive tear film break-up time (NIBUT), and the phenol red thread test (PRT) were assessed. RESULTS: The symptomatic group showed lower K and C thresholds (P < 0.01), greater corneal FL and conjunctival LG staining, and shorter NIBUT than did the non-dry eye group (all others P < 0.05). The OSDI scores were higher in the symptomatic group (P < 0.001). K and C thresholds and NIBUT were inversely correlated with the OSDI and corneal and conjunctival staining (all P < 0.05). The K and C threshold and NIBUT (all P < 0.01) correlated positively. Step-wise multiple regression analysis showed that ocular surface sensitivity and NIBUT were significant predictors of the OSDI. CONCLUSIONS: Ocular irritation assessed with the OSDI is associated with ocular surface hyperesthesia to cooling, corneal epitheliopathy, and tear film instability. Although cause and effect are unclear, the analysis showed that altered corneal and conjunctival sensory processing and tear film attributes are essential aspects of what characterizes dry eye.

Situ,P., Simpson,T. L., Jones,L. W., Fonn,D. Conjunctival and corneal hyperesthesia in subjects with dryness symptoms Optometry and Vision Science 2008;85(9):867-872 [ Show Abstract ]

PURPOSE.: To compare conjunctival and corneal sensitivity in noncontact lens wearing subjects with and without symptoms of ocular dryness, stratified by age and gender. METHODS.: Ninety-seven subjects were enrolled, 54 of whom were asymptomatic and 43 of whom were symptomatic of ocular dryness. A single score for the symptom of dryness was used to classify nondry eye (scores of none to trace) and dry eye symptomatic (scores of mild to severe) groups. The subjects were further stratified into "younger" (19 to 49 years) and "older" age groups (50 to 80 years). Conjunctival and corneal sensitivity of the right eye was measured at the central cornea and temporal conjunctiva, using a computer-controlled pneumatic esthesiometer with stimulus temperature set at 20°C. The ascending method of limits was used to determine the thresholds. RESULTS.: Conjunctival and corneal thresholds were significantly lower in the dry eye symptomatic than in the nondry eye group (both p 0.05). Conjunctival threshold in the nondry eye women was lower than the men (p 0.05). CONCLUSIONS.: Conjunctival and corneal sensitivity to pneumatic cool stimulation is increased in subjects with symptoms of ocular dryness. This hyperesthesia seems to be more significant in the conjunctiva. © 2008 American Academy of Optometry.

Teichroeb,J. H., Forrest,J. A., Jones,L. W., Chan,J., Dalton,K. Quartz crystal microbalance study of protein adsorption kinetics on poly(2-hydroxyethyl methacrylate) Journal of colloid and interface science 2008;325(1):157-164 [ Show Abstract ]

The interaction of macromolecules with artificial biomaterials may lead to potentially serious complications upon implantation into a biological environment. The interaction of one of the most widely used biomaterials, polyHEMA, with lysozyme, bovine serum albumin (BSA), and lactoferrin was investigated using quartz crystal microbalance (QCM). The concentration dependence of adsorption was measured for the aforementioned proteins individually as well as for lysozyme-BSA, and lysozyme-lactoferrin combinations. An extension of Voinova's viscoelastic model to n layers was used to create thickness-time graphs for adsorption. For each of lactoferrin and lysozyme, two distinctly different timescales of adsorption could be differentiated. However, the mechanisms of adsorption appeared to differ between the two. Negative dissipation shifts were measured for low concentrations of lysozyme, trending to positive dissipation at higher concentrations. This suggested that lysozyme was adsorbed initially into the matrix, stiffening the hydrogel, and later onto the surface of polyHEMA. Additionally, trials with commercial no-rub cleaning solutions indicated little added effectiveness over buffer solutions. Mixtures of proteins showed behaviour which differed in some cases from the simple combination of single protein adsorption experiments. Crown Copyright © 2008.

Van Beek,M., Jones,L., Sheardown,H. Hyaluronic acid containing hydrogels for the reduction of protein adsorption Biomaterials 2008;29(7):780-789 [ Show Abstract ]

Recently, new contact lens materials have been introduced which are reported to improve comfort by incorporating wetting agents either in a releasable or nonreleasable form. In the present work, model lens materials based on poly(2-hydroxyethyl methacrylate) (pHEMA) were developed which incorporate releasable or crosslinked and therefore physically entrapped hyaluronic acid (HA) of various molecular weights as a wetting agent. Crosslinked HA, despite being only present in very small amounts, resulted in consistently lower water contact angles over 4 h in comparison to controls, indicating that HA is present at the interface and was not being released over time. The presence of HA in the material was further confirmed by increases in the glass transition temperature measured by differential scanning calorimetry (DSC), and small increases in the stiffness as measured by Instron testing. This crosslinking procedure appeared to have no effect on optical transparency using 35 kDa HA, whereas small decreases in optical transparency at higher wavelengths were noted for the 169 kDa HA crosslinked material, as measured by UV spectrophotometry. Most importantly, protein adsorption results indicated that the adsorption of all proteins studied was considerably decreased by the presence of the small amount of crosslinked HA. The results provide insight into the mechanisms of comfort improvement with commercially available lens materials and suggest that HA containing materials may have significant potential for use in contact lens applications. © 2007 Elsevier Ltd. All rights reserved.

Varikooty,J., Srinivasan,S., Jones,L. Atypical manifestation of upper lid margin staining in silicone hydrogel lens wearers with symptoms of dry eye Contact Lens and Anterior Eye 2008;31(1):44-46 [ Show Abstract ]

Purpose: To report an atypical manifestation of upper lid margin staining (ULMS) that occurred in adapted silicone hydrogel (SH) contact lens wearers who complained of ocular surface dryness. Methods: Sequential staining with sodium fluorescein (FL) and lissamine green (LG) strips was performed in 38 SH lens wearers. The "wiper area" of the upper lid was examined with the slit lamp, at 8× and 12× magnifications. Results: Four out of 38 subjects (10.5%) showed fimbriated or "feathery" extensions from the superior margin of the subtarsal fold onto the upper tarsal plate. The extent of these feathery extensions varied between subjects, with a mean (±S.D.) length of 2 ± 0.8 mm. In all cases a broad band of staining with both FL and LG was demonstrated, which extended along the entire length of the lid margin. Conclusion: The staining patterns shown on the subjects' upper lid margins and tarsal plates suggest that ULMS may include more complex variants. The putative tissue damage revealed through the staining, points to a mechanism not simply restricted to the upper lid margin. © 2007 British Contact Lens Association.

2007

Bitton,E., Keech,A., Simpson,T., Jones,L. Variability of the analysis of the tear meniscus height by optical coherence tomography Optometry and Vision Science 2007;84(9):E903-E908 [ Show Abstract ]

PURPOSE. Tear meniscus height (TMH) is an established parameter indicative of tear film volume and has recently been determined using an optical coherence tomographer (OCT). The purpose of this study was to evaluate the inter and intra observer variability in TMH assessment using OCT. METHODS. Ten subjects (6 M, 4 F; aged 32.5 ± 6.4 years) had 10 consecutive scans taken of their inferior central tear meniscus (5 scans originating at 90° and 5 origination at 270°) using the OCT2 (Humphrey-Zeiss). Images were analyzed by two observers using custom software on three separate occasions. Following a training session among observers, the images were reevaluated to assess differences in variability. Data were analyzed for differences within and across examiners, for the effect of examiner training and between scan directions. RESULTS. The mean TMH and tear volume collapsed across subjects were between 0.24 and 0.25 mm and 25 to 27 nL/mm, respectively. No difference was noted within observers. An interobserver mean volume difference (p = 0.044) was present but was eliminated post training (p = 0.167). Variability was less with scans originating at 90°. CONCLUSIONS. The values of the TMH and tear volume are similar to those reported in the literature. Due to the interobserver differences observed, a training session between examiners may prove to be valuable, especially in a large or multicenter study. © 2007 American Academy of Optometry.

Dracopoulos,A., Dixon,D. G., Jones,L. W., Sivak,J. G., Bantseev,V. In vitro assessment of medical device toxicity: Interactions of benzalkonium chloride with silicone-containing and p-HEMA-containing hydrogel contact lens materials Eye and Contact Lens 2007;33(1):26-37 [ Show Abstract ]

PURPOSE. To analyze the interactions of benzalkonium chloride (BAK) with silicone-containing (lotrafilcon A and galyfilcon A) and p-HEMA-containing (etafilcon A and vifilcon A) hydrogel contact lenses and to examine the possibility of using sodium fluorescein permeability assay (SFPA), 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the bovine lens assay in conjunction with confocal laser scanning microscopy (CLSM) as a battery of in vitro alternatives to evaluate the potential toxicity of soft contact lenses. METHODS. Four soft contact lens types (Focus Monthly [vifilcon A], Focus NIGHT & DAY [lotrafilcon A], ACUVUE Advance With Hydraclear [galyfilcon A], and SUREVUE [etafilcon A]) were soaked for 24 hours in various concentrations of BAK (1%, 0.1%, 0.01%, and 0.001%) in 20-mL glass vials. After 24 hours, the lenses were gently washed in Hanks' Balanced Salt Solution (HBSS), placed in 5 mL of HBSS, and incubated for a total of 7 days at 37°C, 5% CO2. BAK released into HBSS (i.e., the extract) was recovered from the vials and used as the test chemical in the SFPA (epithelium integrity), MTT assay (cellular viability), and the bovine lens assay with CLSM (mitochondrial metabolism and optical properties). The amount of BAK extracted from the various contact lenses was measured using an Abbe refractometer. Negative controls consisted of HBSS and contact lenses subjected to the same conditions as the treated contact lenses, but without BAK. RESULTS. Extracts obtained from soaking Focus Monthly lenses in BAK caused the most damage to the epithelium and mitochondrial metabolism. However, at 0.1% BAK extraction, all lens extracts showed increased levels of back vertex distance variability of the cultured bovine lens. CONCLUSIONS. Unexpectedly, lenses extracted with HBSS showed SFPA and MTT assay responses and an observed effect on the bovine lens epithelium visualized by CLSM, indicating that unknown chemical agents may be leached from contact lens polymers. © 2007 Lippincott Williams & Wilkins, Inc.

Duench,S., Simpson,T., Jones,L. W., Flanagan,J. G., Fonn,D. Assessment of variation in bulbar conjunctival redness, temperature, and blood flow Optometry and Vision Science 2007;84(6):511-516 [ Show Abstract ]

PURPOSE. To assess the diurnal variation in bulbar conjunctival redness, conjunctival temperature, and conjunctival blood flow. METHODS. Bulbar redness was quantified by CIE u' chromaticity using a SpectraScan PR650 spectrophotometer. Conjunctival temperature was measured using a Tasco-Thi 500 infrared thermometer. Measurements of conjunctival blood flow were obtained using a modified Heidelberg Retinal Flowmeter (HRF). Measurements on 10 subjects were made on a periodic basis over the day and on waking. RESULTS. For each factor measured a cyclical pattern was observed, with highest values on waking, a reduction in values towards mid-day, and then a gradual increase over the remainder of the day. There was a significant effect of time for redness, temperature, and conjunctival blood flow (p < 0.001 for all three variables), with no significant difference in the cyclical pattern between eyes being observed (p = NS). CONCLUSIONS. Diurnal bulbar redness, temperature, and conjunctival blood flow variation may be objectively quantified and all three are lowest during the middle of the day and maximal at the start of the day. This information should be considered when undertaking studies in which redness, temperature, and ocular surface blood flow are important outcome variables and time of day is a potential confounding factor. © 2007 American Academy of Optometry.

Fonn,D., Simpson,T., Woods,J., Woods,C. New technologies to assess lens-mediated effects of the cornea Eye and Contact Lens 2007;33(6 PART 2 OF SUPPL 2):364-370 [ Show Abstract ]

Contact lenses can affect the cornea in a variety of ways. Corneal structure can be altered so that its thickness changes to involve the epithelium and the stroma. As a result, the curvature may be affected, but whether it is the front or the back surface that is affected depends on the type of lens used. If thickness increases sufficiently, corneal transparency may decrease. Contact lenses can also affect cellular structure of all layers of the cornea through mechanical trauma, hypoxia, or toxicity from solutions that are used in association with lenses. More serious complications, such as inflammation and infection, can arise. All these changes can be detected by clinicians using slitlamp biomicroscopes and keratometers if the changes are significant enough. Since the development of computers, optical instruments have become more sophisticated and have enabled the detection of subtle changes but have also facilitated more precise measurement of these conditions along with the ability to capture images of the alterations or defects. This article describes some of the newer techniques and, specifically, the application of optical coherence tomography, confocal microscopy, and esthesiometry. © 2007 Lippincott Williams & Wilkins, Inc.

Haque,S., Fonn,D., Simpson,T., Jones,L. Corneal refractive therapy with different lens materials, Part 1: Corneal, stromal, and epithelial thickness changes Optometry and Vision Science 2007;84(4):343-348 [ Show Abstract ]

PURPOSE. To assess the corneal swelling response to two myopic correction corneal refractive therapy (CRT) lenses of varying Dk/t values, worn for a single night. Change in thickness of the total cornea, stroma, and epithelium was measured across the horizontal meridian using optical coherence tomography (OCT). METHODS. In this double-masked, randomized study, twenty subjects wore a CRT design lens in each eye, manufactured from Menicon Z (MenZ; Dk/t = 91) and Equalens II (EqII; Dk/t = 47) materials. Baseline corneal thickness was measured centrally and at four points either side of the central cornea using OCT, the night before sleeping at the Centre for Contact Lens Research. The next morning, lenses were removed, and thickness measurements were repeated 1, 3, 6, and 12 h after removal. RESULTS. On lens removal, the MenZ eye had central and paracentral corneal swelling (mean ± SD) of 4.1 ± 2.0% and 5.6 ± 2.4%, and the EqII eye had 5.8 ± 2.6% and 7.0 ± 2.6%. These values were significantly different from baseline (ReANOVA; p 0.05). Stromal swelling values on lens removal were 5.7 ± 2.2% centrally and 5.5 ± 3.0% mid-peripherally (MenZ) and 7.7 ± 3.1% centrally and 6.6 ± 2.9% mid-peripherally (EqII) (all p < 0.001 from baseline). Central stromal swelling was different between eyes at lens removal (p < 0.001). Stromal thickness in both eyes returned to baseline values within 3 h. CONCLUSION. The higher-Dk/t MenZ material caused significantly less overnight corneal and stromal swelling than the Eqll material, which reinforces the need to prescribe lenses with high Dk/t for overnight wear. Neither central epithelial thinning nor paracentral thickening are significantly affected by Dk/t. © 2007 American Academy of Optometry.

Klenkler,B., Sheardown,H., Jones,L. Growth factors in the tear film: Role in tissue maintenance, wound healing, and ocular pathology Ocular Surface 2007;5(3):228-239 [ Show Abstract ]

Numerous biologically active growth factors are secreted by the lacrimal gland and distributed via the tears over the ocular surface where they affect cellular proliferation, migration, differentiation, and survival. The role of growth factors and their receptors in maintenance of tissue homeostasis and wound healing continues to be elucidated, and the effect of growth factor imbalances In ocular surface diseases is just beginning to be understood. For Instance, in eyes with ocular surface diseases, Including conjunctivitis, corneal erosion, keratitis, and corneal ulcers, epidermal growth factor release rates have been shown to be significantly lower than in normal eyes during reflex tearing. Future research into the mechanisms of dry eye disease will focus on reasons for decreased tear and growth factor production in the neuronal reflex loop or the acinar lacrimal gland cells. Animal models to test therapeutic approaches must be developed. © 2007 Ethis Communications, Inc.

Lorentz,H., Jones,L. Lipid deposition on hydrogel contact lenses: How history can help us today Optometry and Vision Science 2007;84(4):286-295 [ Show Abstract ]

The tear film is a complex fluid that is precisely maintained and which is essential to the health of the ocular surface. One of the major components of the tear film is lipid, which is produced by the meibomian glands and serves many important functions on the ocular surface. It is estimated that there are more than 45 individual lipids within the tear film, which vary greatly in their structure and properties. The composition of the lipid within the tear film has an enormous influence on the stability of the tear film, with a subsequent impact on the occurrence of dry eye and the ultimate success of contact lens wear. The purpose of this review article is to describe the composition of the tear film lipids and their interaction with contact lens materials, with a particular emphasis on how the chemistry of novel silicone hydrogel materials has resulted in clinicians needing to understand the deposition of lipids onto contact lenses and how they may best manage this complication.

Lorentz,H., Rogers,R., Jones,L. The impact of lipid on contact angle wettability Optometry and Vision Science 2007;84(10):946-953

Lu,F., Simpson,T., Sorbara,L., Fonn,D. The relationship between the treatment zone diameter and visual, optical and subjective performance in Corneal Refractive Therapy™ lens wearers Ophthalmic and Physiological Optics 2007;27(6):568-578 [ Show Abstract ]

Purpose: To investigate the stability of the treatment zone (TZ) size during Corneal Refractive Therapy (CRT™) over 4 weeks of lens wear, and to determine the relationship between TZ diameter and visual, optical and subjective performance. Methods: Twenty-three myopic subjects wore CRT™ lenses overnight and removed their lenses on awakening. Visual Acuity (VA), subjective vision, refractive error, aberrations and corneal topography were measured at baseline, immediately after lens removal on the first day and 14 h later, and these measurements were repeated on days 4, 10 and 28. The TZ including the central flattened zone (CFZ) and the annular steepened zone (ASZ) was demarcated by the change in corneal curvature from negative to positive and vice versa, using the tangential difference map from the Atlas corneal topographer. Results: After overnight CRT™ lens wear, the central cornea flattened and the mid-periphery steepened (both p < 0.001). After 4 weeks of lens wear, the CFZ (±SE) increased from 3.41 ± 0.09 mm on day 1 morning to 3.61 ± 0.07 mm on day 28 morning and the diameter of the ASZ increased from 8.17 ± 0.16 mm (day 1 morning) to 8.85 ± 0.14 mm (day 28 morning) (both p < 0.001). From day 10 onwards, the CFZ and ASZ diameter were stable in the morning (p ≥ 0.404). Throughout the day, the CFZ became smaller during the first 10 days (all p ≤ 0.022), whereas the ASZ diameter remained constant (all p ≥ 0.079). There were positive correlations between the CFZ or ASZ and residual refractive error, subjective vision and spherical aberration. The CFZ was also correlated with astigmatism and higher order aberrations, and the ASZ was positively correlated with coma (r = 0.726 to 0.961, all p ≤ 0.042). In addition, there were negative correlations between the CFZ or ASZ and total aberration and defocus and between the ASZ and VA (r = -0.707 to -0.953, all p ≤ 0.050). Conclusion: The TZ changed during the first 10 days. Its size was associated with VA, residual refractive error, aberrations and subjective vision. The concept of a TZ is a useful metric of visual, optical and subjective performance in CRT™ lens wearers. © 2007 The Authors.

Lu,F., Simpson,T., Sorbara,L., Fonn,D. Corneal Refractive Therapy™ with different lens materials, Part 2: Effect of oxygen transmissibility on corneal shape and optical characteristics Optometry and Vision Science 2007;84(4):349-356 [ Show Abstract ]

PURPOSE. To compare the effects of two different oxygen transmissible (Dk/t) lenses on corneal shape and optical performance after one night of corneal refractive therapy (CRT®) for myopia. METHODS. Twenty myopic subjects were fit with Menicon Z (MZ) (Dk/t = 90.6, Paragon CRT® lenses) on one eye and an Equalens II (EII) CRT® lens (Dk/t = 47.2) on the contralateral eye (eye randomized). Corneal topography, refractive error and aberrations were measured before lens insertion (baseline), and the following day after overnight lens wear, on lens removal and 1, 3, 6, 12 h later. Root mean square wavefront errors were measured using 4.5 mm pupils. RESULTS. Averaged over position and time, the horizontal corneal curvature was statistically different between the MZ and EII lens-wearing eyes (p = 0.011). The central cornea flattened similarly (p = 0.886) and the mid-periphery steepened in both eyes (p = 0.061) from baseline. The EII lens-wearing eyes were steeper in the mid-periphery than the MZ eyes immediately after lens removal and at the 1-h visit (p ≤ 0.032). Central corneal flattening and mid-peripheral corneal steepening regressed over time (all p < 0.001) but did not recover to baseline by 12 h (all p < 0.004). Myopia was reduced equally by 0.84 ± 0.83 D for the MZ-lens wearing eyes and 0.84 ± 0.87 D for the EII eyes (p = 0.969). Coma increased from baseline 1.85X (0.056 ± 0.081 μm) for the MZ-lens wearing eyes and 1.72X (0.048 ± 0.084 μm) for the EII eyes (both p < 0.001). Spherical aberration increased from baseline 4.55X (0.101 ± 0.077 μm) for the MZ-lens wearing eyes and 4.31X (0.085 ± 0.076 μm) for the EII eyes (both p < 0.001), but there were no differences between the MZ and EII eyes (all p ≥ 0.308). Coma and spherical aberration did not return to baseline by 12 h (both p ≤ 0.007). CONCLUSIONS. After one night of CRT® lens wear, changes in corneal shape were slightly different, with more mid-peripheral steepening in the EII eyes compared to the MZ eyes. Change in central corneal curvature and optical performance were similar in both eyes. © 2007 American Academy of Optometry.

Lu,F., Sorbara,L., Simpson,T., Fonn,D. Corneal shape and optical performance after one night of Corneal Refractive Therapy™ for hyperopia Optometry and Vision Science 2007;84(4):357-364 [ Show Abstract ]

PURPOSE: To investigate the corneal shape and optical performance following one night of Corneal Refractive Therapy for hyperopia (CRTH). METHODS: Twenty subjects (spherical equivalent: -2.14 +/- 2.54 D) were fit with a Paragon CRTH lens (Dk = 100) on one eye randomly. The other eye served as the control. Aberrations, refractive error, and corneal topography at various locations along the horizontal meridian were measured at baseline prior to lens insertion, and immediately after lens removal and at 1, 3, 6, 12, and 28 hours later. Root mean square wavefront errors were measured using a 4.5 mm pupil size. RESULTS: After one night of CRTH lens wear, the central cornea steepened and paracentral region flattened in the experimental eyes (p < 0.001), whereas no significant location effect was found in the control eyes (p = 0.139). Refractive error (mean +/- SE) changed by 1.23 +/- 0.21 D (p < 0.001). The defocus increased by 0.58 +/- 0.09 microm (p < 0.001). Higher-order aberrations, coma, and spherical aberrations increased by factors of 2.69, 2.58, and 4.07, respectively (all p < 0.001). Spherical aberrations shifted from positive to negative. Astigmatism did not change over time (p = 0.771). All parameters returned to baseline by 28 hours (all p > or = 0.808). Aberrations and refractive error did not change in the control eyes (all p > or = 0.082). CONCLUSIONS.: The CRTH lens steepens the central cornea and flattens the paracentral region, which alters the ametropia by inducing a myopic shift. It appears to be effective for correcting hyperopia and also is reversible.

Luensmann,D., Glasier,M. -A, Zhang,F., Bantseev,V., Simpson,T., Jones,L. Confocal microscopy and albumin penetration into contact lenses Optometry and Vision Science 2007;84(9):839-847 [ Show Abstract ]

Purpose. To develop a novel in vitro method to detect the depth of penetration of the tear film protein albumin into contact lens materials using confocal laser scanning microscopy (CLSM).
Methods. A poly-HEMA-based hydrogel (etafilcon A) and a silicone hydrogel material (lotrafilcon B) were examined. In vitro, bovine serum albumin (BSA) was labeled with 5-(4,6-dichloro-s-triazin-2-ylamino) fluorescein hydrochloride (DTAF). The lenses were incubated in this protein solution (0.5 mg/ml) at 37°C. After 1 and 7 days incubation, the lenses were examined using CLSM (Zeiss 510, config. META 18) and the location of the fluorescently labeled BSA was identified.
Results. BSA adsorption on the surface and penetration into the lens matrix occurred at a higher concentration for etafilcon compared to lotrafilcon (p < 0.001). For both materials, BSA was detected on the surface after 1 day of incubation. Significant levels of BSA were detected within the matrix of etafilcon after as little as 1 day (p < 0.001), but no BSA was detected in the matrix of lotrafilcon at any time (p > 0.05).
Conclusion. CLSM can be successfully used to examine the depth of penetration of fluorescently labeled proteins into various hydrogel polymers. Our results show that etafilcon lenses both adsorb BSA on the surface and absorb BSA within the matrix, whereas lotrafilcon B adsorbs small amounts of BSA on the surface only.

Schulze,M. M., Jones,D. A., Simpson,T. L. The development of validated bulbar redness grading scales Optometry and Vision Science 2007;84(10):976-983 [ Show Abstract ]

PURPOSE: To develop a perceptually and physically based bulbar redness grading scale. METHODS: Digital conjunctival hyperemia photographs were taken using a photo-slit lamp at controlled exposures. Nine participants arranged 25 images on a tabletop over a range of 1.5 m, using separation to represent changes in redness. The position of each image was recorded and normalized for a 0 to 100 scale, and compared to chromaticity of each image obtained using a spectrophotometer. The performance of two versions of the scale (5 and 10 images) and a continuous grading scale was evaluated based on repeatability data collected from nineteen observers who used each scale twice to grade 30 randomly presented images of bulbar redness. RESULTS: Psychophysical scaling was highly correlated between single observers (Pearson's r >or= 0.92, p < 0.05). The averaged subjective grades significantly correlated with chromaticity (r = 0.95 and r = 0.99, p < 0.001 for CIE u* and log u*, respectively). Across all observers, test and retest ratings were highly correlated with either scale (r >or= 0.98), and showed high levels of repeatability expressed by intraclass correlation coefficients (ICC >or= 0.98), correlation coefficients of concordance (CCC >or= 0.96), and coefficients of repeatability (COR <or= 5.64). Despite single unit increment options, the majority of grade values assigned using the discrete scales were distributed in multiples of 5. CONCLUSIONS: Combining psychophysical and physical attributes is a promising method for the development of novel anterior segment scales; the newly developed scales performed well in a clinical setting.

Situ,P., Simpson,T. L., Fonn,D. Eccentric variation of corneal sensitivity to pneumatic stimulation at different temperatures and with CO2 Experimental eye research 2007;85(3):400-405 [ Show Abstract ]

The purpose was to measure corneal sensitivity at multiple corneal positions using pneumatic stimuli, at room temperature and at ocular surface temperature (with and without CO2 added), in 15 healthy participants. Sensitivity of central, mid-peripheral, and peripheral cornea was measured using a computer-controlled modified Belmonte esthesiometer to deliver pneumatic cool (air at 20 °C), mechanical (air at 50 °C), and chemical stimuli (air at 50 °C with CO2 added). The ascending method of limits and method of constant stimuli were adopted to determine the threshold to these stimuli at each location. Sensitivity across the cornea using pneumatic stimuli at different temperatures and chemical stimuli varied only slightly. These patterns of variation are different to what has been previously reported using Cochet-Bonnet esthesiometry. © 2007 Elsevier Ltd. All rights reserved.

Sorbara,L., Simpson,T., Duench,S., Schulze,M., Fonn,D. Comparison of an objective method of measuring bulbar redness to the use of traditional grading scales Contact Lens and Anterior Eye 2007;30(1):53-59 [ Show Abstract ]

Purpose: The primary objective was to compare measures of bulbar redness objectively using a photometric method with standard grading methods. Measures of redness were made on 24 participants wearing a silicone hydrogel contact lens in one eye for overnight wear. This report compares hyperaemia after 1 week of daily wear (baseline) with redness measured after 6 months of overnight wear. Method: A new method of objectively measuring bulbar conjunctival redness was performed using the Spectrascan650® Photometer by Photo Research® under fixed illumination. Photometric measures in CIEu* chromaticity values involve the measurement of chromaticity, a physical analogue of redness, greenness and blueness in the image. This method was validated in Part 1 of the study using repeated measurements on the photographic CCLRU scale. In Part 2 of the study, the photographic grading scale (CCLRU) from 0 (none) to 100 (extreme) was used to make the comparison. Results: Part 1 indicated that the photometer provides a repeatable and reliable measure of bulbar redness (CCC = 0.989). A moderately strong and significant correlation was found between the CIEu* chromaticity values and the analogue data (R = 0.795, p = 0.000) at each measurement session (from baseline to 1 day, 1 week, and 1, 3 and 6 months of overnight wear). Conclusions: This new standardized and objective method of measuring bulbar redness has great potential to replace subjective grading scales, especially with multi-centre studies, where variability between investigators occurs. This method may also detect smaller changes between visits or between eyes. Crown Copyright © 2007.

Srinivasan,S., Chan,C., Jones,L. Apparent time-dependent differences in inferior tear meniscus height in human subjects with mild dry eye symptoms Clinical and Experimental Optometry 2007;90(5):345-350 [ Show Abstract ]

PURPOSE: The aim of the study was to track the volume of tears contained in the inferior tear meniscus over the course of the day in subjects with symptoms of mild dry eye and a control asymptomatic group. METHODS: Forty non-contact lens-wearing subjects (aged 27 +/- 6 years) were enrolled in this investigator-masked study. They were divided into 'dry eye' (DE) and 'non-dry eye' (NDE) individuals based on their responses to the Allergan Subjective Evaluation of Symptoms of Dryness (SESOD) questionnaire. Measurement of the tear meniscus height (TMH) was undertaken on the centre of the right eye at 9:00 am, noon, 3:00 pm, 6:00 pm and 9:00 pm on the lower lid using a non-contact, non-invasive optical coherence tomographer (OCT). The TMH was determined from scanned images using customised software. RESULTS: A monotonous and significant reduction in the central TMH occurred over the course of the day in both groups (p < 0.05), with the values constantly decreasing (NDE = 0.162 to 0.125 mm; DE = 0.154 to 0.121 mm). While the TMH values in the DE group were always lower than the NDE group, these were not significantly different at any time (p > 0.05). CONCLUSIONS: A diurnal reduction in tear volume, as assessed by evaluation of the inferior TMH, may be one of the reasons responsible for the common increase in end-of-day ocular dryness symptoms reported by many patients in clinical practice.

Srinivasan,S., Joyce,E., Jones,L. W. Tear osmolality and ferning patterns in postmenopausal women Optometry and Vision Science 2007;84(7):588-592 [ Show Abstract ]

PURPOSE: To compare tear osmolality and ferning patterns in postmenopausal women (PMW) with and without dry eye symptoms. METHODS: Thirty-seven healthy PMW (>50 years of age), not on hormone replacement therapy, were categorized as being symptomatic or asymptomatic of dry eye based on their responses to an Allergan "Single-Item Score Dry Eye Questionnaire" (SIDEQ). They subsequently completed the Allergan "Ocular Surface Disease Index" (OSDI) questionnaire. Tear samples were collected from participants to evaluate osmolality and ferning patterns. A novel freezing point depression osmometer (Advanced Instruments Inc., Model 3100 Tear Osmometer), was used to measure the osmolality of the tear film. The tear ferning test was performed and evaluated for the quality of ferning based on the Rolando grading system. RESULTS: SIDEQ responses revealed 21 symptomatic and 16 asymptomatic participants. The OSDI total score was 6.5 +/- 5.9 for the non-dry-eyed (NDE) group and 25.7 +/- 12.4 for the dry-eyed (DE) group. The subscores for the DE group were significantly greater than the NDE group (p < 0.001). Osmolality values in DE individuals were significantly different from NDE (328.1 +/- 20.8 vs. 315.1 +/- 11.3 mOsm/kg; p = 0.02). Fifty percent of the DE participants showed type II ferning patterns and 29% of the DE participants showed type III ferning patterns, whereas the NDE participants showed either type I (44%) or II (66%) ferning patterns. There was a significant difference between the DE and NDE participants for the ferning patterns (p = 0.019). There was no significant correlation between tear osmolality and tear ferning (DE: r = 0.12; p > 0.05, NDE: r = -0.17; p > 0.05). CONCLUSIONS: Osmolality in mild and moderately DE PMW is higher than in NDE PMW and tear ferning is a rapid, simple, noninvasive laboratory procedure that indicates altered tear quality in PMW with symptoms of dry eye.

Subbaraman,L. N., Glasier,M. A., Senchyna,M., Sheardown,H., Jones,L. Extraction efficiency of an extraction buffer used to quantify lysozyme deposition on conventional and silicone hydrogel contact lens materials Eye and Contact Lens 2007;33(4):169-173 [ Show Abstract ]

PURPOSE: Extracting lysozyme from Food and Drug Administration group IV etafilcon lenses by using 0.2% trifluoroacetic acid and acetonitrile (TFA/ACN) is a well-established procedure. TFA/ACN has been the extraction buffer of choice for extracting proteins from silicone hydrogel contact lenses. The purpose of this study was to determine the efficiency of TFA/ACN in extracting lysozyme from silicone hydrogel and etafilcon lenses by using an in vitro model. METHODS: ACUVUE 2, Focus NIGHT & DAY, O2 Optix, PureVision, and ACUVUE Advance lenses were incubated in simple lysozyme solution and a complex artificial tear solution consisting of multiple tear components containing lysozyme labeled with iodine 125. All the silicone hydrogel lenses were incubated for 28 days, whereas the ACUVUE 2 lenses were incubated for 7 days at 37 degrees C with constant rotation. After the incubation period, radioactive counts were determined, and the lenses were placed in an appropriate volume of the buffer for 24 hours in darkness. The lenses were removed from the buffer, and radioactive counts were determined again. RESULTS: Extraction efficiencies for lysozyme from the artificial tear solution were 97.2% +/- 1.2% for ACUVUE 2, 64.3% +/- 6.2% for Focus NIGHT & DAY, 62.5% +/- 5.6% for O2 Optix, 53.5% +/- 5.8% for PureVision, and 89.2% +/- 3.4% for ACUVUE Advance. Results were similar for the lysozyme extracted after incubating in the simple lysozyme solution. CONCLUSIONS: TFA/ACN is extremely efficient at extracting lysozyme deposited on etafilcon lenses. However, it does not extract all the lysozyme deposited on silicone hydrogel lenses, and alternative extraction procedures should be sought.

Suwala,M., Glasier,M. -A, Subbaraman,L. N., Jones,L. Quantity and conformation of lysozyme deposited on conventional and silicone hydrogel contact lens materials using an in vitro model Eye and Contact Lens 2007;33(3):138-143 [ Show Abstract ]

PURPOSE: To determine the activity of hen egg lysozyme (HEL) deposited on conventional and silicone hydrogel contact lens materials by using an in vitro model. METHODS: ACUVUE 2 (etafilcon A), PureVision (balafilcon A), ACUVUE Advance (galyfilcon A), Focus NIGHT & DAY (lotrafilcon A), O2 Optix (lotrafilcon B), Proclear (omafilcon A), and ACUVUE OASYS (senofilcon A) contact lenses were deposited in vitro in a phosphate-buffered solution (PBS) containing 2 mg/mL HEL. Lenses were briefly rinsed in PBS to remove unbound material and extracted in a mixture of acetonitrile and trifluoroacetic acid. After lyophilization, extracts were examined for lysozyme activity by micrococcal assay and total protein by Western blot. RESULTS: In terms of total protein accumulation, ACUVUE 2 showed the most, with 1,800 microg per lens. Proclear was next, with 68 microg per lens, and Focus NIGHT & DAY showed the least, with 2 microg per lens. ACUVUE Advance, ACUVUE OASYS, and O2 Optix accumulated similar amounts of lysozyme, at approximately 6 microg per lens. Lysozyme deposited on ACUVUE 2 showed the greatest activity (91% +/- 5%), and this result was statistically different from all other lens types (P<0.001). Lysozyme deposited on Focus NIGHT & DAY (24% +/- 5%) and O2 Optix (23% +/- 11%) showed the lowest activity. Lysozyme deposits on other lens materials showed intermediate activity (ACUVUE Advance, 60% +/- 15%; ACUVUE OASYS, 51% +/- 9%; PureVision, 58% +/- 8%; and Proclear, 38% +/- 3%). CONCLUSIONS: Silicone hydrogel lenses acquire less lysozyme deposit than conventional group II (Proclear) or group IV (ACUVUE 2) lenses do, and the levels of activity of the lysozyme are highly variable between materials.

Woods,C. A., Jones,D. A., Jones,L. W., Morgan,P. B. A seven year survey of the contact lens prescribing habits of Canadian optometrists Optometry and Vision Science 2007;84(6):505-510 [ Show Abstract ]

PURPOSE: Little is known about the contact lens prescribing habits of optometrists in North America. The purpose of this survey was to obtain data on the types of lenses and solutions prescribed by Canadian optometrists. METHODS: One thousand Canadian optometrists were surveyed annually over seven consecutive years (2000 to 2006; n = 7000) on their contact lens prescribing preferences. Each survey requested a range of information about the contact lenses prescribed to the first 10 patients after its receipt. RESULTS: Over this time period, 1008 (14.4%) of the surveys were returned, providing data on 9383 fits. During the seven-year period, the ratio of male:female fits was 1:2 (3123:6217, 43 not reported), with a mean age of 31.3 +/- 13.6 years (range 2 to 82 years). The ratio of new fits to refits was 2:3 (3780:5518, 85 not reported), with 91.3% of all fits being soft contact lenses (SCL). Of the SCL fits, 59.5% were spherical, 28.5% toric, 9.7% multifocal, and 2.3% cosmetic tints. Gas permeable (GP) fits were 46.6% spherical, 18.6% toric, 19.5% multifocal, and 6.6% were for orthokeratology (OK). Over the seven-year period, SCL prescribed for continuous wear (CW) increased from 3.2% to 14.3% between 2000 and 2004 and reduced to 8.1% in 2006, for all fits. The use of mid-water content (MWC) materials decreased from 34.6% to 2.7% and the use of silicone hydrogel (SH) lenses increased from 61.4% to 96.2%, for all CW fits. GP lens continuous wear increased from 0.7% to 30.6% of all GP lens fits by 2006. Daily wear (DW) of SH lenses decreased from 49.6% (2000) to 33.7% (2004) and then increased to 86.1% in 2006, for SH fits. MWC SCL fit on a monthly planned replacement (PR) basis reduced in popularity over the seven-year period (75.0% to 39.9%) and in 2006 more patients were fit overall with SH lenses (42.9%). The use of non-PR SCL declined from 20.5% to 4.5% of all fits. Fitting of low-water content lenses also declined (15.1% to 7.0%). High-water content (5.4% to10.2%) and SH lenses (5.4% to 42.9%) both increased. By 2006, the majority of GP lenses fit were with high Dk (HDK) materials (50.3%). CONCLUSIONS: The preferred contact lens modality for Canadian optometrists appears to be DW SCL, which are replaced monthly. The proportion of lenses used for CW peaked in 2004, with SH SCL being the preferred material. The market share for GP lenses remains relatively unchanged, with an increasing proportion used for OK and CW. The launch of DW SH lenses in 2004 resulted in a marked increase in their reported fits, with a similar effect following the launch of a HDK GP lens material for CW.

2006

Begley,C. G., Himebaugh,N., Renner,D., Liu,H., Chalmers,R., Simpson,T., Varikooty,J. Tear breakup dynamics: A technique for quantifying tear film instability Optometry and Vision Science 2006;83(1):15-21 [ Show Abstract ]

PURPOSE: The purpose of this study was to develop a novel, quantitative measurement of tear film breakup dynamics (TBUD) to study the phenomenon of tear breakup in dry eye and control subjects and its impact on dry eye symptoms. METHODS: Ten control and 10 dry eye subjects completed the Dry Eye (DEQ) and other questionnaires. After the instillation of sodium fluorescein, subjects kept the tested eye open for as long as possible, similar to a staring contest, while tear film breakup was videotaped (S-TBUD). The maximum blink interval (MBI) and tear breakup time (TBUT) were measured from digital movies by a masked observer. Individual frames of movies were converted to gray-scale images, maps of relative tear film fluorescence were generated, and the total area of tear breakup (AB) of the exposed cornea was quantified. RESULTS: On average, dry eye subjects demonstrated a higher AB and shorter TBUT and MBI, but only the AB was significantly different (p = 0.023). Subjects most often used the descriptors stinging and burning to describe their sensations during staring trials. The AB showed a high correlation between eyes and with some DEQ symptom measures. CONCLUSIONS: These methods allow objective quantification and tracking of the phenomenon of tear breakup. Our results suggest that tear breakup stresses the corneal surface, resulting in stimulation of underlying nociceptors. The tear film of dry eye subjects was less stable than controls. They had a larger AB measured from the last video frame before MBI (i.e., just before blinking) than did controls. This perhaps reflects adaptation to the repeated stress of tear instability in dry eye.

Dumbleton,K., Keir,N., Moezzi,A., Feng,Y., Jones,L., Fonn,D. Objective and subjective responses in patients refitted to daily-wear silicone hydrogel contact lenses Optometry and Vision Science 2006;83(10):758-768 [ Show Abstract ]

PURPOSE. Silicone hydrogel (SiH) lenses offer many physiological advantages for daily wear (DW) in addition to the continuous-wear modality for which they were originally developed. The purpose of this study was to investigate the clinical performance and physiological responses in a group of successful long-term wearers of conventional hydrogel lenses when refitted with DW SiH contact lenses. METHODS. Eighty-seven successful soft lens wearers (8.4 ± 4.7 years of prior lens wear) participated in this study. Bulbar and limbal hyperemia were subjectively graded and digitally photographed for subsequent masked objective evaluation. Subjective symptoms were scored using visual analog scales. In addition, refractive error, corneal curvature, and corneal thickness were measured. All subjects were refitted with Focus Night & Day (lotrafilcon A) SiH lenses; however, to reduce the potential for bias, they were informed that they were being randomly assigned to wear either low oxygen permeability (Dk) lenses or high Dk SiH lenses and were "masked" as to their lens assignment. Subjects returned after 1 week, 1 month, and 2 months of DW, at which time all gradings, photographs, and measurements were repeated. End-of-day subjective symptoms were also graded periodically during the study. RESULTS. Ninety-three percent of subjects were successfully refitted. Both objective and subjective evaluations showed that bulbar and limbal hyperemia decreased significantly in all quadrants during the study (p < 0.001), particularly for those subjects with greater baseline hyperemia (p < 0.001). Subjects reported a concurrent reduction in end-of-day dryness and improved end-of-day comfort compared with their habitual lenses (p < 0.001). No significant changes in refractive error, tarsal papillary response, corneal curvature, or corneal thickness were found during the study. CONCLUSIONS. Hyperemia in contact lens wearers may be attributed to a number of factors, including hypoxia. Refitting existing low Dk lens wearers with SiH lenses on a DW basis can result in a decrease in hyperemia, which may be significant for some subjects and also results in improvements in symptoms of dryness and discomfort. © 2006 American Academy of Optometry.

Haque,S., Simpson,T., Jones,L. Corneal and epithelial thickness in keratoconus: A comparison of ultrasonic pachymetry, Orbscan II, and optical coherence tomography Journal of Refractive Surgery 2006;22(5):486-493 [ Show Abstract ]

PURPOSE: To compare corneal thickness measurements in individuals with keratoconus using optical coherence tomography (OCT), Orbscan II, and ultrasonic pachymetry and to measure epithelial and stromal thickness in these individuals using OCT. METHODS: Twenty individuals with keratoconus and 20 controls (without keratoconus) were enrolled. The Orbscan II was used to locate the steepest area of the cornea, which was taken to represent the cone apex. Each instrument was used to obtain four total corneal thickness measurements-from the cone apex, corneal center, mid-nasal, and mid-temporal cornea. Optical coherence tomography scans were analyzed to provide epithelial and stromal thickness readings. RESULTS: In individuals with keratoconus, mean central corneal thickness (CCT) measured by ultrasonic pachymetry, Orbscan, and OCT was 494.2±50.0 μm, 438.6±47.7 μm, and 433.5±39.7 μm, respectively. The central keratoconic cornea was 57.7 μm thinner than the normal cornea (post-hoc P.05). CONCLUSIONS: Ultrasonic pachymetry produced the highest corneal thickness readings in the center and apex, compared to Orbscan II and OCT. Centrally, the total cornea, epithelium, and stroma were thinner in individuals with keratoconus than in normal individuals.

Lu,F., Simpson,T., Fonn,D., Sorbara,L., Jones,L. Validity of pachymetric measurements by manipulating the acoustic factor of Orbscan II Eye and Contact Lens 2006;32(2):78-83 [ Show Abstract ]

PURPOSE. To assess the validity of pachymetric measurements by examining the constancy of the acoustic factor (AF) of the Orbscan II (Orbtek, Bausch & Lomb, Rochester, NY) after overnight rigid gas-permeable (RGP) contact lens wear. METHODS. Twenty participants wore CRT (Paragon Vision Sciences, Mesa, AZ) HDS 100 contact lenses on one eye and control lenses on the contralateral eye for one night while sleeping. Another 24 participants wore CRT lenses on both eyes for one night. Central corneal thickness was measured using optical coherence tomography and Orbscan II on the night before lens use, immediately after lens removal on the following morning, and 1, 3, 6, and 12 hours later. By using optical coherence tomography as a reference, the adjusted AF was calculated by using a least squares method over time. RESULTS. The adjusted AF depended on the corneal thickness in normally hydrated corneas. The adjusted AF and the percentage change of the adjusted AF varied before and after overnight lens wear. There was a strong and significant correlation between the corneal swelling and the percentage change of the adjusted AF (all r at least 0.91, P<0.05). CONCLUSIONS. The adjusted AF is a variable, not a constant. The AF is a function of the corneal thickness and its alteration with, for example, corneal swelling. The validity of the adjusted Orbscan II pachymetric measures using a single AF is untenable. © 2006 Lippincott Williams & Wilkins, Inc.

Moezzi,A. M., Fonn,D., Simpson,T. L. Overnight corneal swelling with silicone hydrogel contact lenses with high oxygen transmissibility Eye and Contact Lens 2006;32(6):277-280 [ Show Abstract ]

PURPOSE. To compare central corneal swelling after 8 hours of sleep in eyes wearing 2 different silicone hydrogel lenses with high oxygen transmissibility. METHODS. Twenty neophyte subjects were randomly assigned to wear a comfilcon A lens (CooperVision Inc) in one eye and a lotrafilcon A lens (CIBA Vision) in the contralateral eye for an 8-hour overnight period. The study was repeated with another 20 neophyte subjects wearing comfilcon A in one eye only and no lens in the contralateral control eye. Central corneal thickness was measured with optical pachometry before lens insertion, immediately after lens removal on waking, at 20 and 40 minutes, 1 hour, 2 hours and 3 hours. RESULTS. There was no significant difference between the amount of overnight central corneal swelling induced by the 2 lenses (4.1% ± 1.9% with comfilcon A vs. 4.0% ± 1.7% with lotrafilcon A; P>0.05). The swelling of the comfilcon A lens-wearing eyes was significantly higher than that found in the non-lens-wearing contralateral eyes (4.5% ± 2.1% vs. 3.0% ± 1.7%; P<0.05). CONCLUSIONS. The same amount of overnight corneal swelling was induced by the 2 study lenses. The higher overnight swelling observed with the comfilcon A lenses compared to the non-lens-wearing eyes is similar to that reported in the literature for studies using lotrafilcon A lenses. © 2006 Lippincott Williams & Wilkins, Inc.

Moezzi,A. M., Sin,S., Simpson,T. L. Novel pachometry calibration Optometry and Vision Science 2006;83(6):E366-E371 [ Show Abstract ]

PURPOSE: The purpose of this study was to develop a simple method for cross-calibrating instruments that measure corneal thickness. METHODS: Fourteen rigid lenses of different thicknesses were manufactured using a material with refractive index of 1.376. Center thickness of the lenses (CT) was measured using a computerized optical pachometer (OP), two optical coherence tomographers (OCTs), and a confocal microscope (CM). Accuracy of measurements was compared between the four instruments. RESULTS: Before calibrating the machines, there was a significant effect of the measurement device (p < 0.05). The differences between instruments were eliminated (p > 0.05) after applying calibration equations for each device. In addition, after each instrument was calibrated with lenses of 1.376 refractive index, there was no significant difference (p > 0.05) between measured values of lens center thickness by OP, each OCT, CM, and the physical center thickness of the lenses. CONCLUSIONS: Using calibration lenses with the same refractive index as the cornea (1.376) allows rapid and simple calibration of the pachometers so that corneal thickness measurements from different devices can be used interchangeably.

Sin,S., Simpson,T. L. The repeatability of corneal and corneal epithelial thickness measurements using optical coherence tomography Optometry and Vision Science 2006;83(6):360-365 [ Show Abstract ]

PURPOSE.: The purpose of this study is to examine within and between session repeatability of clinical optical coherence tomography (OCT) imaging for anterior segment morphometry. METHODS.: Images of the corneal apex of each eye in 18 subjects were obtained using a Humphrey Zeiss OCT imager. Subjects viewed a target positioned to ensure that scans were orthogonal to the ocular surface and each image, consisting of 100 adjacent sagittal scans, analyzed using custom software. Repeatability data were analyzed using intraclass correlation coefficients (ICCs), correlation coefficient of concordance (CCC, perfect test-retest agreement ICC or CCC = 1.0), and coefficients of repeatability (COR, 95% confidence interval of test-retest differences). To account for each eye, the multivariate repeatability statistic Iota was estimated. RESULTS.: Mean central corneal and epithelial thickness of 32 eyes (OD and OS combined) is 536 ± 26 μm (standard deviation [SD]) and 52 ± 3 μm (SD) with 5th and 95th percentile thicknesses of 507 and 591 μm for central cornea and 48 and 57 μm for central epithelial. Worst case within session repeatability was defined as repeatability between images with greatest differences in mean thickness within a session. Corneal thickness worst case ICC was 0.95 and COR was ± 9.98 μm. Epithelium worst case ICC was 0.36, CCC was 0.12, and COR was ± 11.11 μm. First image between session corneal thickness had an ICC = 0.98 and a COR = 10.83 μm, whereas epithelium ICC = 0.38, CCC = 0.37, and COR was ± 12.84 μm. When we compared the average of the first three tests with the first three retest images, corneal ICC was 0.98 and COR was ± 10.64 μm and epithelium ICC = 0.73, CCC = 0.72, and COR was ± 6.53 μm. Iota (multivariate repeatability, using eye as a factor) for the cornea was at least 0.96 (worst case) and increased to at least 0.98 when within-session image data were averaged. Iota for epithelium measures ranged from 0.29 when first images were compared with 0.57 when within-session image data were averaged. CONCLUSIONS.: There is very good repeatability of corneal thickness measurement using OCT; even the worst case measurements are similar between sessions. On the other hand, this is not the case for epithelium measurements, and if multiple images within a session are acquired, the worst case results demonstrate how important it is to optimize each OCT scan and also average multiple scans to maximize intersession repeatability. Copyright © 2006 American Academy of Optometry.

Subbaraman,L. N., Bayer,S., Glasier,M. -A, Lorentz,H., Senchyna,M., Jones,L. Rewetting drops containing surface active agents improve the clinical performance of silicone hydrogel contact lenses Optometry and Vision Science 2006;83(3):143-151 [ Show Abstract ]

PURPOSE: The purpose of this study was to investigate the impact of using a rewetting drop (RWD) containing surface active agents (OPTI-FREE RepleniSH; Alcon, Fort Worth, TX) on the clinical performance and protein deposition when using a continuous-wear (CW) silicone hydrogel (SH) contact lens. METHODS: Subjects wore lotrafilcon A SH lenses on a 30-day CW basis for two consecutive 1-month periods while inserting either 0.9% unpreserved unit-dose saline (control) or multidose OPTI-FREE RepleniSH (test RWD). Subjective comfort and symptoms were assessed after 2 and 4 weeks with each product. After 1 month of wear with each product, lenses were collected and analyzed in the laboratory for total protein, total lysozyme, and percentage of denatured lysozyme. RESULTS: Symptoms of dryness and comfort varied across the day regardless of drop type (p < 0.001) with dryness being maximal on waking, least in the middle of the day, and increased towards the evening. The test RWD provided greater comfort on insertion (p = 0.02), better visual quality (p < 0.01), and less mucous discharge on waking (p = 0.02) than the control product. Lysozyme deposition was significantly reduced after the use of the test RWD as compared to saline (0.73 +/- 0.5 microg/lens vs. 1.14 +/- 0.7 microg/lens; p < 0.001) as was total protein deposition (1.17 +/- 0.7 microg/lens vs. 1.86 +/- 0.8 microg/lens; p < 0.001). Lysozyme denaturation was also reduced with the use of the test RWD compared with the control (76 +/- 10% vs. 85 +/- 7%; p < 0.01). CONCLUSIONS: The use of a RWD containing surface active agents provided greater subjective satisfaction, reduced lysozyme and total protein deposition, and reduced denatured lysozyme than a RWD containing saline alone.

Subbaraman,L. N., Glasier,M. -A, Senchyna,M., Sheardown,H., Jones,L. Kinetics of in vitro lysozyme deposition on silicone hydrogel, PMMA, and FDA groups I, II, and IV contact lens materials Current eye research 2006;31(10):787-796 [ Show Abstract ]

We sought to compare the kinetics of in vitro lysozyme deposition on silicone hydrogel (SH), polymethyl methacrylate (PMMA), and FDA groups I, II, and IV contact lenses. Lenses were incubated in 125I-labeled lysozyme for time periods ranging from 1 hr to 28 days, and radioactive counts were determined. SH lenses and PMMA deposited less lysozyme than conventional hydrogel lenses (p < 0.05). Lysozyme accumulation on group IV lenses reached a maximum on the seventh day and then plateaued, whereas on groups I, II, and SH lenses, deposition continued to increase across all time periods, reiterating that kinetics of lysozyme deposition is highly material dependent.

Teichroeb,J. H., Forrest,J. A., Ngai,V., Jones,L. W. Anomalous thermal denaturing of proteins adsorbed to nanoparticles European Physical Journal E 2006;21(1):19-24 [ Show Abstract ]

We have used localized surface plasmon resonance (LSPR) to monitor the structural changes that accompany thermal denaturing of bovine serum albumin (BSA) adsorbed onto gold nanospheres of size 5nm-60nm. The effect of the protein on the LSPR was monitored by visible extinction spectroscopy. The position of the resonance is affected by the conformation of the adsorbed protein layer, and as such can be used as a very sensitive probe of thermal denaturing that is specific to the adsorbed protein. The results are compared to detailed calculations and show that full calculations can lead to significant increases in knowledge where gold nanospheres are used as biosensors. Thermal denaturing on spheres with diameter > 20 nm show strong similarity to bulk calorimetric studies of BSA in solution. BSA adsorbed on nanospheres with d ≤ 15nm shows a qualitative difference in behavior, suggesting a sensitivity of denaturing characteristics on local surface curvature. This may have important implications for other protein-nanoparticle interactions. © EDP Sciences, Società Italiana di Fisica and Springer-Verlag 2006.

2005

Chalmers,R. L., Begley,C. G., Edrington,T., Caffery,B., Nelson,D., Snyder,C., Simpson,T. The agreement between self-assessment and clinician assessment of dry eye severity Cornea 2005;24(7):804-810 [ Show Abstract ]

Purpose: The purpose of this analysis was to measure the degree of agreement between clinicians' assessment and subjects' self-assessment of dry eye severity in a cross-sectional, observational dry eye study. A secondary purpose was to identify the role of gender and age in that concordance. Methods: In a cross-sectional observational study, 162 dry eye subjects and 48 controls were recruited from clinical databases of ICD-9 codes in 6 clinical sites. Before examination, subjects gave a global self-assessment of the severity of their dry eye from "none" to "extremely severe." After a clinical examination that included dry eye tests, the clinician discussed the subjects' symptoms and then gave global clinician assessment of dry eye from "none" to "severe." We measured the degree of agreement in these global measures. Results: Although the correlation and agreement between clinician and self-assessment was significant (r = 0.720, P = 0.000; weighted K = 0.471; 95% CI = 0.395, 0.548; P = 0.000), the clinician assessment underestimated the severity in 40.9% of the subjects by at least 1 grade compared with the subjects' self-assessment. Over 54% of subjects over age 65 and 43% of the female subjects had their condition underestimated by the clinician (P < 0.05). Conclusions: Clinicians often relatively underestimated the severity of the subjects' self-assessment of dry eye in this clinical study, especially among the elderly and women. Eye care practitioners need better, more quantitative tools for the assessment of ocular surface symptoms to improve the concordance in severity assessment and to meet the needs of this symptomatic patient population by offering them appropriate treatments. Copyright © 2005 by Lippincott Williams & Wilkins.

Feng,Y., Simpson,T. L. Comparison of human central cornea and limbus in vivo using optical coherence tomography Optometry and Vision Science 2005;82(5):416-419 [ Show Abstract ]

Purpose. The purpose of this study was to compare central corneal and limbal total and epithelial thickness using a commercially available optical coherence tomographer. Methods. A Humphrey-Zeiss Optical Coherence Tomographer (OCT [Carl Zeiss, Meditec, Dublin, CA]) was used to obtain corneal images from 10 subjects. Central corneal and limbal total and epithelial thickness of both eyes were measured using the OCT. Each OCT image comprised 100 measurements, 10 nasal, 10 central, and 10 temporal measurements from each image were analysed. Results. The central corneal and epithelial thickness of the right and the left eyes were 507.9 ± 35.8 μm, 58.4 ± 2.5 μm, 506.9 ± 37.4 μm, and 58.5 ± 2.5 μm, respectively. There were no differences between eyes (p > 0.05). The nasal and temporal limbal total and epithelial thickness of the right and left eyes were 703.8 ± 32.1 μm, 704.9 ± 31.0 μm, 76.8 ± 3.5 μm, 77.9 ± 2.9 μm, 704.4 ± 31.8 μm, 706.3 ± 32.5 μm, 77.5 ± 2.8 μm, and 77.8 ± 2.5 μm, respectively. There were no differences between the nasal and temporal total and epithelial thickness of both eyes (p > 0.05). However, there was a statistical difference between the central corneal and limbal total and epithelial thickness (both p < 0.05). Conclusions. Central cornea and limbus are measurably different using OCT. Central cornea is thinner than limbus for both total thickness and epithelial thickness. There is no difference between eyes of central corneal and limbal total and epithelial thickness. Optical Coherence Tomography is a useful instrument for in vivo human limbal morphometry. Copyright © 2005 American Academy of Optometry.

Feng,Y., Simpson,T. L. The inhibitory interaction between human corneal and conjunctival sensory channels Investigative Ophthalmology and Visual Science 2005;46(4):1251-1255 [ Show Abstract ]

PURPOSE. To explore human corneal and conjunctival sensory channels at suprathreshold level. METHODS. Ten healthy human subjects participated in the study. The Belmonte pneumatic esthesiometer was used to apply mechanical and chemical stimuli to the central cornea and temporal conjunctiva of the left eye. Stimuli were applied in a paired and unpaired way for conjunctival stimulation. A 100-point visual analog scale (VAS) was used to rate the intensity of the stimulus. RESULTS. The magnitudes of the sensation evoked from the conjunctiva were different when using different methods for presenting stimuli to the ocular surface. When stimuli were applied to the conjunctiva alone, the magnitude of the sensation was stronger than when the stimuli were applied in pairs to the cornea and conjunctiva for both mechanical (P = 0.04) and chemical (P = 0.02) stimulation. CONCLUSIONS. The relatively strong discomfort evoked from the cornea appears to suppress partially the relatively weaker conjunctival stimulation. This manifested as the conjunctival sensory transducer function being shallower (less intense sensation) when immediately preceded by corneal stimulation than when the conjunctival sensory transducer functions were measured alone (unpaired). The underlying mechanism could be adaptation or some other inhibitory effect, such as diffuse noxious inhibitory control. At some level therefore, corneal and conjunctival sensory channels are not independent. Copyright © Association for Research in Vision and Ophthalmology.

Fonn,D., Bruce,A. S. A review of the Holden-Mertz criteria for critical oxygen transmission Eye and Contact Lens 2005;31(6):247-251 [ Show Abstract ]

Purpose. Holden and Mertz established the foundations for the new generation of silicone hydrogel contact lenses for daily and extended wear in 1984. Absence of lens-induced corneal swelling was their premise and although this was possible with daily wear, the