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.

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.

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

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

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.

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;44(6):1202-1214 [ 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.

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.

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.

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.

Darge,H., Addisu,K. D., Tsai,H-C., Birhan,Y. S., Hanurry,E. Y., Mekonnen,T. W., Gebrie,H. T., Arunagiri,V., Thankachan,D., Wu,T-Y., Chang,H-M., Huang,C-C., Wu,S-Y Actively Targeting Redox-Responsive Multifunctional Micelles for Synergistic Chemotherapy of Cancer ACS Omega 2024;9(32):34268-34280 [ Show Abstract ]

Stimuli-responsive polymeric micelles decorated with cancer biomarkers represent an optimal choice for drug delivery applications due to their ability to enhance therapeutic efficacy while mitigating adverse side effects. Accordingly, we synthesized a digoxin-modified novel multifunctional redox-responsive disulfide-linked poly(ethylene glycol-b-poly(lactic-co-glycolic acid) copolymer (Bi(Dig–PEG-PLGA)-S2) for the targeted and controlled release of doxorubicin (DOX) in cancer cells. Within the micellar aggregate, the disulfide bond confers redox responsiveness, while the presence of the digoxin moiety acts as a targeting agent and chemosensitizer for DOX. Upon self-assembly in aqueous solution, Bi(Dig–PEG-PLGA)-S2 formed uniformly distributed spherical micelles with a hydrodynamic diameter (Dh) of 58.36 ± 0.78 nm and a zeta potential of −24.71 ± 1.01 mV. The micelles exhibited desirable serum and colloidal stability with a substantial drug loading capacity (DLC) of 6.26% and an encapsulation efficiency (EE) of 83.23%. In addition, the release of DOX demonstrated the redox-responsive behavior of the micelles, with approximately 89.41 ± 6.09 and 79.64 ± 6.68% of DOX diffusing from DOX@Bi(Dig–PEG-PLGA)-S2 in the presence of 10 mM GSH and 0.1 mM H2O2, respectively, over 96 h. Therefore, in HeLa cell lines, DOX@Bi(Dig–PEG-PLGA)-S2 showed enhanced intracellular accumulation and subsequent apoptotic effects, attributed to the targeting ability and chemosensitization potential of digoxin. Hence, these findings underscore the promising characteristics of Bi(Dig–PEG-PLGA)-S2 as a multifunctional drug delivery vehicle for cancer treatment.

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.

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

Dengis,C. A., Simpson,T. L., Steinbach,M. J., Ono,H. The Cyclops effect in adults: Sighting without visual feedback Vision research 1998;38(2):327-331 [ Show Abstract ]

When asked to look through a tube, younger children place it at the bridge of the nose, and not over one eye: the Cyclops effect. This is a natural response to a median plane egocenter. With maturity, the Cyclops effect disappears as we learn to overcame the consequences of an egocenter between the two eyes, and instead, to use the 'preferred' eye. We videotaped adults (n = 14) and children with normal vision (n = 30), children with comitant strabismus (n = 14), and adults and children (n = 14) with one eye enucleated as they attempted to look through a plastic tube. Immediately in front of the face was a liquid crystal window that could be either transparent or opaque. As the tube was raised, the window was made opaque-blocking sight of the target, their hands, and the tube. Most binocular observers placed the tube approximately at the bridge of the nose. This was significantly different from the response of the enucleated observers who put the tube 75% of the way to the remaining eye (P = 0.0001). All observers align, on average, with the measured location of their egocenter when asked to perform a monocular task without visual cues. Deprived of visual feedback, binocular observers show the Cyclops effect, regardless of age.

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.

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.

Doughty,M. J., Fonn,D. Pleomorphism and endothelial cell size in normal and polymegethous human corneal endothelium International Contact Lens Clinic 1993;20(5-6):116-123 [ Show Abstract ]

The normal human corneal endothelium is composed of a tessellated mosaic of cells with different numbers of sides. A number of published studies indicate that while six-sided cells predominate (58-74%), significant numbers of five-sided (13-22%) and seven-sided (11-18%) are present along with occasional four-, eight-, nine- and even 10-sided cells. In polymegethous endothelia (associated with polymethyl methacrylate [PMMA] lenses and extended wear soft contact lenses [EW SCL]), the decline in the percentage of six-sided cells is associated with increases in the percentage of four-, five-, seven-, or eight-sided cells. Our analysis of photo slit-lamp micrographs revealed that the four- or five-sided cells tend to be smaller than the six-sided cells, whereas the seven-sided or larger cells are larger than six-sided cells. As a result, analyses of the average areas of each cell type indicate that the greater the pleomorphism (associated with polymegethism) the steeper the slope of a plot relating cell areas to the number of cell sides. The relationship is not necessarily linear (as suggested in previous reports), but does indicate that the remodeling of the endothelium (when significant cell loss is not evident) may follow some formal ordered process. © 1993.

Doughty,M. J., Fonn,D., Nguyen,K. T. Assessment of the reliability of calculations of the coefficient of variation for normal and polymegethous human corneal endothelium Optometry and Vision Science 1993;70(9):759-770 [ Show Abstract ]

In endothelial morphometry, uncertainty exists concerning how many cells should be measured. A study was undertaken to calculate mean cell area and coefficient of variation (COV) of cell areas using different numbers of cells from photo-slitlamp pictures and published micrographs. Groups of 65, 95, or 165 tesselated cells were measured and area and COV values calculated in progressive sets of 5 cells; each pair of values was compared to that obtained using all cells in each group. The results show that, for both normal (homomegethous) and irregular (polymegethous) endothelia, even cell counts as low as 50 cells can usually provide average cell area values that are within 1 to 2% of the values estimated from larger groups of cells. A similar reliability was observed for estimates of COV for normal endothelia. However, for polymegethous endothelia, even with 100 cells analyzed, the estimates of COV generally only approached a +/- 4% reliability. This uncertainty in COV estimates should be considered in both comparative studies and in regression analyses of COV changes over time or other variables.

Doughty,M. J., Fonn,D., Richter,D., Simpson,T., Caffery,B., Gordon,K. A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada Optometry and Vision Science 1997;74(8):624-631 [ Show Abstract ]

Objective. To collect questionnaire data from patients in a large clinical population that would allow for an estimate of the prevalence of self-reported symptoms of dry eyes. Methods. A 13-point questionnaire (The Canada Dry Eye Epidemiology Study, CANDEES) was mailed to all optometric practices in Canada in October 1994, with the request that it be completed by 30 successive nonselected patients. Results. Four hundred fifty sets of questionnaires (total, 13,517) were analyzed (a 15.7% return rate) from patients aged from 80 years; 55% were in the 21- to 50-year age group; 60.7% were female; and 24.3% were contact lens wearers. A total of 28.7% reported dry eye symptoms, of whom 24.2% reported concurrent dry mouth, 24.5% had worse symptoms in the morning, 30.3% reported concurrent lid problems, and 35.7% reported a history of allergies. Of the 3716 patients reporting symptoms, 62 (1.6%) were in the 'severe' category and 290 (7.8%) were in the 'constant but moderate' category. Contact lens wear, concurrent allergies, dry mouth, lid problems, or use of medications increased the chance of a patient reporting dry eye symptoms. Conclusions. The prevalence of patients reporting any level of symptoms of dry eyes was approximately 1 in 4; severe symptoms were reported by 1 in 225 patients.

Doughty,M. J., Potvin,R., Pritchard,N., Fonn,D. Evaluation of the range of areas of the fluorescein staining patterns of the tarsal conjunctiva in man Documenta Ophthalmologica 1995;89(4):355-371 [ Show Abstract ]

Fluorescein dye is commonly used to highlight the tarsal conjunctiva in man to facilitate diagnosis of papillary conjunctivitis. A quantitative analysis of the fluorescein-highlighted features could be useful in both assignment of severity grades as well as for objective comparisons but no data is available on the distributions of sizes (areas) of these features. An exploratory, range-finding study was undertaken to provide data on feature areas that might be encountered. After application of fluorescein, 35 mm photographs were taken at a fixed distance with zone 1/zone 2 (Allansmith) of the tarsal plate aligned perpendicular to the camera. The photographs were projected, an overlay of 150 to 180 contiguous features outlined by fluorescein made and planimetry used to assess the areas and area distributions of the features on tarsal plates clinically graded with stages 1 to 4 papillary hypertrophy. For zone 1 of the tarsal plate in asymptomatic subjects, a fluorescein solution highlights the limits of features that enclose an area averaging 30,000 μm2 (range 8000 to 120,000; median area of close to 35,000 μm2). The areas of these features were generally normally distributed and there was little variation in feature areas across the zone. At different stages of clinical papillary conjunctivitis, the areas of the negative staining patterns are larger. Averages of 60,000 to 90,000 μm2, median values of close to 70,000 μm2 and individual feature areas up to 350,000 μm2 were seen in mildly symptomatic patients. These distributions were generally heterogeneous and showed a skewed distribution. Areas averaging up to 0.755 mm2 (range 0.6 to 3.2 mm2) were measured in moderate to severe papillary hypertrophy.

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.

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.

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.

Du Toit,R., Pritchard,N., Heffernan,S., Simpson,T., Fonn,D. A comparison of three different scales for rating contact lens handling Optometry and Vision Science 2002;79(5):313-320 [ Show Abstract ]

Purpose. To compare the validity, responsiveness, and reliability of three subjective rating scales applied to soft contact lens (SCL) handling. Methods. Fifty-four adapted SCL wearers handled three different types of lenses on two occasions and rated the handling with each scale: visual analogue scales (VAS), 20-interval visual analogue scales with descriptors (VAD) and Likert rating scales with five intervals (LRS). Results. There were significant differences between the scales (p < 0.01) and between the subjective ratings of lens handling (p < 0.001). VAS showed the least variability, exhibited the highest construct validity, were the most responsive, and were the most reliable: interclass correlations (0.63), coefficient of repeatability (27.5), and correlation between test and retest (Spearman r = 0.65, [all p < 0.05]). Higher repeatability, because of the fewer intervals of LRS, was not demonstrated and, generally, LRS was the least satisfactory scale. Handling was rated as easiest using VAD and most difficult using LRS. Conclusions. Although all three scales can be used to provide measures of lens handling, VAS may provide a simple and repeatable tool for measuring subjective responses.

Du Toit,R., Simpson,T. L., Fonn,D., Chalmers,R. L. Recovery from hyperemia after overnight wear of low and high transmissibility hydrogel lenses Current eye research 2001;22(1):68-73 [ Show Abstract ]

Purpose. To measure the limbal vascular response after 8 hours of eye closure while wearing high and low permeability lenses compared to control eyes without lenses. Method. Twenty neophyte participants wore lotrafilcon A silicone hydrogel lenses (HDk; Dk = 140) or etafilcon A hydrogel lenses (LDk; Dk = 18). On two different nights the lenses were randomly worn for 8 hours during sleep in the right eyes only. Left eyes were non-lens wearing controls. Biomicroscopic images of the temporal limbal area were videotaped at baseline, on eye opening and every 20 minutes for 3 hours. A masked observer graded digitized images of the limbal area. Results. On waking and after lens removal there were no differences in hyperemia between the HDk and LDk lens wearing eyes. There were also no differences at any time between the HDk lens wearing eyes and their control eyes (p > 0.05). On waking the eyes wearing the LDk lens were more hyperemic compared to baseline (p < 0.001) and compared to their control eyes at 20 (p < 0.001) and 180 minutes (p = 0.01), indicating slower recovery from hyperemia. The HDk lens wearing eyes recovered to their baseline levels by 180 minutes (p = 0.99), compared to the LDk lens wearing eyes, which had not recovered to baseline levels by 180 minutes (p = 0.04). Conclusion. The reduction in hyperemia over time of the HDk lens wearing eyes was the same as the controls. The LDk lens wearing eyes were more hyperemic than the controls on waking and the reduction in hyperemia over time was slower. This suggests that the slower recovery from hyperemia may be affected by the lower oxygen transmissibility of the LDk lens.

Du Toit,R., Situ,P., Simpson,T., Fonn,D. The effects of six months of contact lens wear on the tear film, ocular surfaces, and symptoms of presbyopes Optometry and Vision Science 2001;78(6):455-462 [ Show Abstract ]

Purpose. To assess the tear film, ocular surfaces, and symptoms of ocular discomfort in a presbyopic population before and after contact lens wear. Methods. A total of 150 presbyopes (49% were previous soft contact lens wearers) participated in a clinical trial in which they wore either monovision (single vision Acuvue lenses) or Acuvue Bifocal contact lenses. Clinical measurements of tear film, biomicroscopy, and corneal sensitivity as well as subjective ratings using the Dry Eye Questionnaire were collected at the initial visit and repeated after 6 months. Comparisons were made between age groups (40 to 51 years and 52 to 71 years) and genders before and after contact lens wear. Associations between objective and subjective tests were sought. Results. After 6 months of contact lens wear, clinical signs had worsened by less than one-half of a grade, and tear break up time (TBUT) worsened by 3 s. Only TBUT was lower for the older age group. Females had less bulbar hyperemia, more sensitive eyes, more lissamine green staining, and lower TBUT and phenol red thread measurements (all p lt; 0.04). Twenty-eight percent experienced dryness before contact lens wear, but this figure increased to 68% when wearing contact lenses. There were no age differences, but almost twice as many females as males reported dryness. Reporting symptoms of dryness was associated with gender, corneal sensitivity, and type of corneal staining. Conclusions. These results provide a representation of the ocular surface condition and symptoms of ocular discomfort in the middle-aged population and seem similar to reports of younger populations. Wearing contact lenses seems to influence dry eye symptoms more than age or gender. Therefore, presbyopes should not be excluded from consideration for contact lens fitting.