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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Regan,D., Simpson,T. Multiple sclerosis can cause visual processing deficits specific to texture-defined form Neurology 1995;45(4):809-815 [ Show Abstract ]

We performed the following tests in 25 patients with multiple sclerosis (MS) and 25 age-matched control subjects: recognition of texture-defined (TD) letters; recognition of motion-defined (MD) letters; and recognition of luminance-defined (LD) letters of 96% and 11% contrasts. Six patients with normal visual acuity were abnormal on recognizing TD letters, of whom one gave normal results on all other tests. Eleven patients were abnormal on MD letter recognition, of whom four gave normal results on all other tests. Visual acuity for letters of 11% contrast were abnormally low in seven patients, of whom two gave normal results on all other tests. We conclude that the neural mechanisms underlying recognition of TD, MD, and low-contrast LD letters in subjects with normal visual acuity are sufficiently different that they can be differentially damaged by MS. Therefore, TD, MD, and LD letter tests provide complementary information. We suggest that the detection of TD letters can be disrupted by demyelination of long-range horizontal connections between orientation-tuned neurons in the striate cortex.

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

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

Robinson,B., Feng,Y., Woods,C. A., Fonn,D., Gold,D., Gordon,K. Prevalence of visual impairment and uncorrected refractive error-report from a canadian urban population-based study Ophthalmic epidemiology 2013;20(3):123-130 [ Show Abstract ]

Purpose: The prevalence of visual impairment due to uncorrected refractive error has not been previously studied in Canada. A population-based study was conducted in Brantford, Ontario. Methods: The target population included all people 40 years of age and older. Study participants were selected using a randomized sampling strategy based on postal codes. Presenting distance and near visual acuities were measured with habitual spectacle correction, if any, in place. Best corrected visual acuities were determined for all participants who had a presenting distance visual acuity of less than 20/25. Results: Population weighted prevalence of distance visual impairment (visual acuity <20/40 in the better eye) was 2.7% (n=768, 95% confidence interval (CI) 1.8-4.0%) with 71.8% correctable by refraction. Population weighted prevalence of near visual impairment (visual acuity <20/40 with both eyes) was 2.2% (95% CI 1.4-3.6) with 69.1% correctable by refraction. Multivariable adjusted analysis showed that the odds of having distance visual impairment was independently associated with increased age (odds ratio, OR, 3.56, 95% CI 1.22-10.35; 65 years compared to those 39-64 years), and time since last eye examination (OR 4.93, 95% CI 1.19-20.32; 5 years compared to 2 years). The same factors appear to be associated with increased prevalence of near visual impairment but were not statistically significant. Conclusions: The majority of visual impairment found in Brantford was due to uncorrected refractive error. Factors that increased the prevalence of visual impairment were the same for distance and near visual acuity measurements. © 2013 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.

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

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

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

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

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

Samsom,M., Chan,A., Iwabuchi,Y., Subbaraman,L., Jones,L., Schmidt,TA In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4) Tribology International 2014;89:27-33

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

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

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

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

Schulze,M. M., Hutchings,N., Simpson,T. L. The use of fractal analysis and photometry to estimate the accuracy of bulbar redness grading scales Investigative Ophthalmology and Visual Science 2008;49(4):1398-1406 [ Show Abstract ]

Purpose. To use physical attributes of redness to determine the accuracy of four bulbar redness grading scales, and to cross- calibrate the scales based on these physical measures. Methods. Two image-processing metrics, fractal dimension (D) and percentage of pixel coverage (% PC), as well as photometric chromaticity were selected as physical measures, to describe and compare grades of bulbar redness among the McMonnies/Chapman-Davies scale, the Efron Scale, the Institute for Eye Research scale, and a validated scale developed at the Centre for Contact Lens Research. Two sets of images were prepared by using image processing: The first included multiple segments covering the largest possible region of interest (ROI) within the bulbar conjunctiva in the original images; the second contained modified scale images that were matched in size and resolution across scales, and a single, equally-sized ROI. To measure photometric chromaticity, the original scale images were displayed on a computer monitor, and multiple conjunctival segments were analyzed. Pearson correlation coefficients between each set of image metrics and the reference image grades were calculated to determine the accuracy of the scales. Results. Correlations were high between reference image grades and all sets of objective metrics (all Pearson's r ≥ 0.88, P ≤ 0.05); each physical attribute pointed to a different scale as being most accurate. Independent of the physical attribute used, there were wide discrepancies between scale grades, with almost no overlap when cross-calibrating and comparing the scales. Conclusions. Despite the generally strong linear associations between the physical characteristics of reference images in each scale, the scales themselves are not inherently accurate and are too different to allow for cross-calibration. Copyright © Association for Research in Vision and Ophthalmology.

Schulze,M. M., Hutchings,N., Simpson,T. L. The perceived bulbar redness of clinical grading scales Optometry and Vision Science 2009;86(11):E1250-E1258 [ Show Abstract ]

Purpose. To use a psychophysical scaling method to estimate the perceived redness of reference images of the McMonnies and Chapman-Davies (six reference levels), Institute for Eye Research (four), Efron (five), and Validated Bulbar Redness (five) bulbar redness grading scales. Methods. Regions of interest were cropped out of the grading scale reference images; three separate image sets (color, grayscale, and binarized) were created for each scale, combining to a total of 20 images per image set. Ten naïve observers were asked to arrange printed copies of the 20 images per image set across a distance of 1.5 m on a flat surface, so that separation reflected their perception of bulbar redness; only start and end point of this range were indicated. The position of each image was averaged across observers to represent the perceived redness for this image, within the 0 to 100 range. Subjective data were compared with physical attributes (chromaticity and spatial metrics) of redness. Results. For each image set, perceived redness of the reference images within each scale was ordered as expected, but not all consecutive within-scale levels were rated as having different redness. Perceived redness of the reference images varied between scales, with different ranges of severity being covered by the images. Perception of redness severity depended on the image set (repeated-measures analysis of variance; all p ≤ 0.0002). The perceived redness was strongly associated with the physical attributes of the reference images. Conclusions. Subjective estimates of redness are based on a combination of chromaticity and vessel-based components. Psychophysical scaling of perceived redness lends itself to being used to cross-calibrate these four clinical scales. © 2009 American Academy of Optometry.

Schulze,M. M., Hutchings,N., Simpson,T. L. The conversion of bulbar redness grades using psychophysical scaling Optometry and Vision Science 2010;87(3):159-167

Schulze,M. M., Hutchings,N., Simpson,T. L. Grading bulbar redness using cross-calibrated clinical grading scales Investigative Ophthalmology and Visual Science 2011;52(8):5812-5817 [ Show Abstract ]

Purpose. To determine the between-scale agreement of grading estimates obtained with cross-calibrated McMonnies/Chapman- Davies (MC-D), Institute for Eye Research (IER), Efron, and Validated Bulbar Redness (VBR) grading scales. Methods. Modified reference images of each grading scale were positioned on a desk according to their perceived redness (within a 0 to 100 range) as determined in a previous psychophysical scaling experiment. Ten observers were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Only 0 and 100 were marked on the scale, but not the numerical position of the reference images. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. Results. Overall, perceived redness depended on the sample image and the reference scale used (repeated measures ANOVA; P = 0.0008); six sample images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability ranged from five units (IER vs. VBR) to eight units (IER vs. Efron) of the 0 to 100 range. Conclusions. The use of cross-calibrated reference grades for bulbar redness grading scales allows comparison of grading estimates obtained with different scales. Perceived redness is dependent on the dynamic range of the reference images of the scale, with redness estimates generally being found to be higher for scales with a shorter dynamic range. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Schulze,M. M., Jones,D. A., Simpson,T. L. The development of validated bulbar redness grading scales Optometry and Vision Science 2007;84(10):976-983 [ Show Abstract ]

PURPOSE: To develop a perceptually and physically based bulbar redness grading scale. METHODS: Digital conjunctival hyperemia photographs were taken using a photo-slit lamp at controlled exposures. Nine participants arranged 25 images on a tabletop over a range of 1.5 m, using separation to represent changes in redness. The position of each image was recorded and normalized for a 0 to 100 scale, and compared to chromaticity of each image obtained using a spectrophotometer. The performance of two versions of the scale (5 and 10 images) and a continuous grading scale was evaluated based on repeatability data collected from nineteen observers who used each scale twice to grade 30 randomly presented images of bulbar redness. RESULTS: Psychophysical scaling was highly correlated between single observers (Pearson's r >or= 0.92, p < 0.05). The averaged subjective grades significantly correlated with chromaticity (r = 0.95 and r = 0.99, p < 0.001 for CIE u* and log u*, respectively). Across all observers, test and retest ratings were highly correlated with either scale (r >or= 0.98), and showed high levels of repeatability expressed by intraclass correlation coefficients (ICC >or= 0.98), correlation coefficients of concordance (CCC >or= 0.96), and coefficients of repeatability (COR <or= 5.64). Despite single unit increment options, the majority of grade values assigned using the discrete scales were distributed in multiples of 5. CONCLUSIONS: Combining psychophysical and physical attributes is a promising method for the development of novel anterior segment scales; the newly developed scales performed well in a clinical setting.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Simpson,T. Monocular acuity in the presence and absence of fusion Optometry and Vision Science 1992;69(5):405-410 [ Show Abstract ]

Because little is known about monocular acuity during binocular fusion, acuity of the right eye was measured in binocularly normal subjects, with the fellow eye open or fully occluded. The target was flashed for 65 ms or presented sinusoidally for 1 s. Subjects had both eyes optimally focused, or the right eye defocused by +3.00 D. Monocular acuities were equivalent during fusion or occlusion when both eyes were optimally focused. Acuity of the defocused eye was reduced when the fellow eye was open compared to when it was occluded. Suppression of the blur, therefore, produced a measurable reduction in recognition thresholds. As monocular acuity was not measurably affected by the fellow eye when each eye was in focus, the finding that monocular vision is improved with the fellow eye occluded should be ascribed to something other than suppression or more sensitive spatial measures of the suppression should be obtained.

Simpson,T. L. Effect of asymmetry on calculations of convergence in prism diopters Optometry and Vision Science 1993;70(3):201-204 [ Show Abstract ]

Calculations of convergence in units of prism diopters are based on an assumption that convergence is symmetrical, that is, the visual axes intersect on the median plane. The effect of departure from symmetrical convergence is shown to produce systematic errors in calculations of convergence distance, if the convergence angle is constrained to be constant. On the other hand, if the convergence distance is constrained to be constant, departure from symmetry results in a systematic reduction in the convergence angle. Because these errors are disregarded in the specification of convergence in prism diopters, care should be taken in using these units for larger amounts of asymmetrical convergence.

Simpson,T. L. A comparison of six methods to estimate thresholds from psychometric functions Behavior Research Methods Instruments & Computers 1995;27(4):459-469 [ Show Abstract ]

There are many ways in which to estimate thresholds from psychometric functions. However, almost nothing is known about the relationships between these estimates. In the present experiment, Monte Carlo techniques were used to compare psychometric thresholds obtained using six methods. Three psychometric functions were simulated using Naka-Rushton and Weibull functions and a probit/logit function combination. Thresholds were estimated using probit, logit, and normit analyses and least-squares regressions of untransformed or z-score and logit-transformed probabilities versus stimulus strength. Histograms were derived from 100 thresholds using each of the six methods for various sampling strategies of each psychometric function. Thresholds from probit, logit, and normit analyses were remarkably similar. Thresholds from z-score- and logit-transformed regressions were more variable, and linear regression produced biased threshold estimates under some circumstances. Considering the similarity of thresholds, the speed of computation, and the ease of implementation, logit and normit analyses provide effective alternatives to the current ''gold standard''-probit analysis-for the estimation of psychometric thresholds.