Peer-reviewed Articles

Please use the year list below to look at past 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.

Guthrie,S., Luensmann,D., Schulze,M., Woods,J., Jones,L. Investigation of Delefilcon A Contact Lenses for Symptomatic Daily Disposable Contact Lens Wearers with Dry Eye Disease: A Prospective Comparative Study Clinical Ophthalmology 2024;Online ahead of print [ Show Abstract ]

Purpose: This prospective comparative study aimed to assess the effects on contact lens comfort, dryness, and wear time when symptomatic daily disposable (DD) contact lens (CL) wearers were refit with delefilcon A (DT1) lenses.

Patients and methods: Thirty five symptomatic DD CL wearers with dry eye disease as determined according to the TFOS DEWS 2 guidelines, were enrolled and completed the study. Participants wore their habitual DD CLs during an initial assessment and were subsequently refit with DT1 for one month. Participants were masked to the study lens type. Subjective ratings of end-of-day comfort and dryness, average wear time, and comfortable wear time were evaluated as primary endpoints.

Results: Of the 35 participants, two participants were classified as aqueous deficient dry eye, while the remaining participants exhibited symptoms primarily due to evaporative causes. The median CLDEQ-8 score for dryness significantly improved from 17 (fair) with habitual lenses to 13 (good) with DT1 lenses (p<0.01). Participants reported significantly better end-of-day comfort (p=0.01) and less end of day dryness (p=0.01) with DT1 compared to their habitual DD lenses. The comfortable wear time was significantly longer with DT1 (8.5 ± 4.1 hours) compared to habitual DD lenses (6.7 ± 3.2 hours) (p=0.04). No significant differences were observed in vision ratings (p=0.07).

Conclusion: Refitting symptomatic DD CL wearers with DT1 resulted in improved end-of-day comfort, reduced end-of-day dryness, and extended comfortable wear time compared to their habitual lenses. These findings suggest that DT1 may offer benefits for symptomatic DD wearers with dry eye disease.

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.

Laughton,D., Hill,J. S., McParland,M., Tasso,V., Woods,J., Zhu,X., Young,G., Craven,R., Hunt,C., Neitz,J., Neitz,M., Chalberg,T., Jones,D., Wolffsohn,J. Control of myopia using diffusion optics spectacle lenses: 4-year results of a multicentre randomised controlled, efficacy and safety study (CYPRESS) BMJ Open Ophthalmology 2024;9.e001790 [ Show Abstract ]

Aims To evaluate the myopia control efficacy of Diffusion Optics Technology (DOT) spectacle lenses in children over a 4-year treatment period.

Methods CYPRESS Part 1 (NCT03623074) was a 3-year multicentre, randomised, controlled, double-masked trial comparing two investigational spectacle lens DOT designs (Test 1, Test 2) and standard single vision Control lenses in 256 North American children aged 6–10 years. Children completing Part 1 (n=200) were invited to enrol in CYPRESS Part 2 (NCT04947735) for an additional 1-year period. In Part 2, Test 1 (n=35) and Control groups (n=42) continued with their original lens assignment and the Test 2 group (n=21) were crossed over to Test 1 (DOT 0.2) lenses. The co-primary endpoints were change from baseline in axial length (AL) and cycloplegic spherical equivalent refraction (cSER).

Results Test 1 spectacle lenses demonstrated superiority to the Control in both co-primary endpoints: with a difference between means (Test 1−Control) of −0.13 mm for AL (p=0.018) and 0.33 D for cSER (p=0.008) in Part 1 and −0.05 mm for AL (p=0.038) and 0.13 D for cSER (p=0.043) in Part 2. Comparing treatment effects in Part 1 and 2 suggests that COVID-19 public health restrictions negatively impacted treatment efficacy in study years 2 and 3.

Conclusion DOT 0.2 spectacle lenses are safe and effective at reducing myopia progression, with additional benefit evident in year 4 of wear. These results support the hypothesis that a mild reduction in retinal contrast can slow myopia progression in young children. The unprecedented disruption in participant schooling and lifestyle during the COVID-19 pandemic may have depressed treatment efficacy in Part 1.

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. Evaluating the in vitro wettability and coefficient of friction of a novel and contemporary reusable silicone hydrogel contact lens materials using an in vitro blink model 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.