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PurposeThe purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.MethodsParticipants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (r s ); 95% confidence intervals (95% CI) accounted for intereye correlation.ResultsAmong 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation r s = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (r s = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (r s = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (r s from -0.07 to 0.05).ConclusionsIn the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

SignificanceLipid deficiency due to meibomian gland (MG) dysfunction is believed to account for the vast majority of patients with dry eye compared with aqueous deficiency. Clinicians commonly evaluate MG length to determine a disease, but our research with isotretinoin users suggests that MG contrast is also an important characteristic to consider.PurposeThis study aimed to determine the sensitivity and specificity of MG contrast for the diagnosis of lipid-deficient dry eye (LDDE).MethodsThis case-control study used demographic data, Standard Patient Evaluation of Eye Dryness (SPEED) scores, average tear lipid layer thickness (TLLT), fluorescein tear breakup time (FTBUT), upper eyelid meibography images, and meibum quality and quantity scores for individuals with LDDE (SPEED score ≥10 and TLLT ≤35 interferometric color units) and normal individuals (SPEED ≤2 and TLLT ≥80 interferometric color units).ResultsThirty-one eyes of 22 controls (mean ± SD age, 22.7 ± 5.5 years) and 13 eyes of 12 cases (mean ± SD age, 43.9 ± 17.2 years) were included. Normalized MG contrast was significantly correlated with FTBUT (r = 0.35, P = .02), percent MG atrophy (r = -0.50, P < .001), and SPEED scores (r = -0.49, P < .001). The receiver operating characteristic curve for LDDE diagnosis classifiers MG contrast, MG atrophy, and meibum quantity score had areas under the curve of 0.83, 0.64, and 0.73, respectively. Meibomian gland contrast cutoff at 28.3 intensity units yielded optimal correct classification of subjects (84.1%; sensitivity, 0.69; specificity, 0.90). Cases had shorter FTBUT (P < .001), worse meibum quality (P = .02) and quantity (P = .02) scores, and lower MG contrast (P < .001) compared with controls. Subjects with low MG contrast (≤28.3) had 14.9 higher odds of having LDDE (95% confidence interval, 2.84 to 78.4) compared with subjects with high MG contrast (>28.3).ConclusionsMeibomian gland contrast correlates well with clinical parameters and symptoms, shows good sensitivity and excellent specificity for diagnosing LDDE, and can be a useful diagnostic parameter for monitoring MG changes due to age, disease, or intervention.

PurposeTo examine the relationship between pre-corneal and pre-contact lens tear film stability (TFS), and to determine whether pre-corneal TFS is a reliable predictor of subsequent pre-lens TFS after a contact lens is placed on the eye.Methods667 records met inclusion criteria and were extracted from a soft contact lens multi-study database. Multivariable linear mixed effects models were fit to examine the association between pre-corneal and pre-lens TFS, adjusting for potential confounders and accounting for repeated measures. Receiver Operating Characteristic (ROC) analysis was employed to assess the predictive performance of pre-corneal TFS for subsequent pre-lens TFS. TFS was quantified for this analysis as the non-invasive tear breakup time (NITBUT).ResultsPre-corneal NITBUT was significantly related to the pre-lens NITBUT at both 10 min (p

The surface of the human eye is covered with a protective tear film that refreshes with each blink. Natural blinking occurs involuntarily, but one can also voluntarily blink or refrain from blinking. The maximum time one can refrain from blinking until the onset of discomfort is the maximum interblink period (MIBP). During the interblink period the tear film evaporates and thins from the ocular surface. Infrared thermography provides a non-invasive measure of the ocular surface temperature (OST). Due to evaporation, ocular surface cooling (OSC) generally occurs when the eyes are open and exposed to the environment. The purpose of our study was to investigate the effect of OSC rate on the MIBP, and to investigate the association of the MIBP with tear film characteristics in subjects who do and do not exhibit OSC. The MIBP was measured simultaneously with OST over time. Non-invasive tear breakup time, tear meniscus height, tear lipid layer thickness, and Schirmer I test strip wetted lengths were measured on a day prior to the thermography visit. Subjects were divided into cooling and non-cooling groups based on OSC rate, and demographic and tear film characteristics were tested for inter-group differences. A faster OSC rate was associated with an exponentially shorter duration of the MIBP overall and within the cooling group alone. Faster non-invasive tear breakup time was significantly associated with a shorter MIBP in both groups. These results suggest that tear film evaporation initiates a pathway that results in the onset of ocular discomfort and the stimulus to blinking. The presence of a subset of subjects with no or minimal OSC who nevertheless have a short MIBP indicates that evaporative cooling is not the only mechanism responsible for the onset of ocular discomfort.

SignificanceThis study evaluated the effects scleral lens wear has on corneal health using fluorometry and in vivo confocal microscopy. No subclinical changes on healthy corneas of young subjects were observed during 3 months of scleral lens wear.PurposeThis study aimed to evaluate the effects 3 months of scleral lens wear has on the corneal epithelial barrier function, dendritic cell density, and nerve fiber morphology.MethodsTwenty-seven neophytes (mean [standard deviation] age, 21.4 [3.9] years) wore scleral lenses of a fluorosilicone acrylate material bilaterally (97 Dk, 15.6 to 16.0-mm diameter) for 3 months without overnight wear. Subjects were randomized to use either Addipak (n = 12) or PuriLens Plus (n = 15) during lens insertion. Measurements of corneal epithelial permeability to fluorescein were performed with automated scanning fluorophotometer (Fluorotron Master; Ocumetrics, Mountain View, CA) on the central cornea of the right eye and the temporal corneal periphery of the left eye. Images of the distributions of corneal nerve fibers and dendritic cells and nerve fibers were captured in vivo with a confocal laser scanning microscope (Heidelberg Retina Tomograph, Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany) on the central and inferior peripheral cornea of the left eye. Corneal measurements and imaging were performed at baseline and after 1 and 3 months of lens wear.ResultsThe corneal permeability values in natural log, dendritic cell densities, and nerve fiber morphology did not significantly change from baseline to 1 and 3 months of lens wear, for both central and peripheral corneal regions (P > .05). Dendritic cell density at the inferior cornea was higher than the central cornea throughout the study (P < .001). No relationships were observed between each outcome measurements and the saline solution groups (P > .05).ConclusionsScleral lens wear for 3 months on healthy cornea of young subjects did not affect corneal epithelial barrier function, nerve fiber, and dendritic cell densities. Buffered and nonbuffered saline solutions impacted the corneal health in similar ways.

ObjectivesTo compare subjective and clinical outcomes in three study groups: (1) asymptomatic contact lens (CL) wearers (ASYM); (2) symptomatic CL wearers who become asymptomatic on lens removal; and (3) symptomatic CL wearers who do not resolve on lens removal.MethodsNinety-two subjects completed the Berkeley Dry Eye Flow Chart with and without lenses, ocular surface examinations, and a battery of questionnaires.ResultsThirty-seven subjects (40%) were ASYM, 30 (33%) had contact lens-induced dry eye (CLIDE), and 25 (27%) had underlying physiological DE. Visual Analog Scale ratings, OSDI score, and SPEED score were significantly better for the ASYM group (P

PurposeTo report a diffuse lamellar keratitis (DLK) cluster attributed to autoclave reservoir biofilm and to review the risk and prevention of DLK and toxic anterior segment syndrome (TASS) caused by such biofilms.SettingRefractive Surgery Center, University of California, Berkeley.DesignObservational case-control study and review of literature.MethodsEyes were evaluated for DLK following laser in situ keratomileusis (LASIK) over a 5-year period. Multiple changes in surgical and operating room protocols were prompted by a cluster of DLK cases. The autoclave reservoir chamber wall was cultured for microbial contamination. The MEDLINE database was used to identify relevant past publications.ResultsFrom January 7, 2010, to December 18, 2014, 1115 eyes received LASIK. Between September 2, 2010, and June 11, 2012, 147 eyes of 395 LASIK cases developed DLK (37.2%). Systematic modifications in surgical protocols were unsuccessful in ending the prolonged cluster of DLK cases until the STATIM 2000 autoclave was replaced with a new STATIM autoclave and a reservoir sterilization and surveillance protocol implemented. Over the subsequent 30 months, DLK incidence was reduced to 2.2% (14 DLK cases from 632 total LASIK cases, P < .0001). The retired autoclave reservoir chamber wall cultures grew Pseudomonas aeruginosa and the Burkholderia cepacia complex.ConclusionsFluid reservoirs of tabletop steam autoclaves can readily develop polymicrobial biofilms harboring microbial pathogens, whose inert molecular byproducts can cause DLK and TASS when introduced to the eye by surgical instruments. Stringent reservoir cleaning and maintenance may significantly reduce this risk by preventing and removing these biofilms.

PurposeWomen have a higher dry eye disease prevalence compared with men, although only relatively minor differences in the ocular surface have been observed. Interestingly, a sex difference in pain sensitivity is known, and recent research suggests that pain sensitivity is associated with dry eye symptoms. This study attempts to discern whether the association between pain sensitivity and dry eye symptoms varies between women and men.MethodsIn this prospective cross-sectional study, subjects were seen for one visit where they were asked to fill out a set of questionnaires consisting of the Pain Sensitivity Questionnaire, Ocular Surface Disease Index (OSDI), and other dry eye questionnaires. This was followed by an ocular surface assessment on both eyes.ResultsTwo hundred eighty-seven subjects (194 women, 93 men) completed the study. Intersex differences in the ocular surface were noted. Even after accounting for these differences, an interaction effect between sex and Pain Sensitivity Questionnaire-minor score on dry eye symptoms was observed, with only women noting increased symptoms on the OSDI (P < 0.005) and other dry eye questionnaires (P values ranging from 0.01 to

PurposeTo investigate the effect of various oxygen transmissibilities (Dk/t) of scleral lenses and corneal thickness recovery time from overnight eye closure with patching on corneal edema during 5 h lens wear.MethodsScleral lenses (hofocon A, 15.6 mm diameter) were worn bilaterally with three different Dks (100, 140, and 160 Barrer). Central and peripheral corneal thickness (CCT and PCT) were measured using optical coherence tomography. Four subjects were randomly selected for one additional visit and asked to patch one eye before night sleeping. The patch was not removed until lens insertion to avoid corneal deswelling. Then CCT of both eyes was measured.ResultsTen neophytes with healthy eyes participated in the study. Mean [95% CI] Dk/t of the study lenses was 32.0 [29.2, 34.7] hBarrer/cm. Mean [95% CI] CCT immediately upon lens insertion and after 5 h of lens wear were 532.4 [520.3, 544.5] μm and 538.7 [526.5, 551.0] μm, respectively. Mean [95% CI] percentage change (%Δ) in CCT was 1.2% [0.9%, 1.5%], 1.2% [0.9%, 1.4%], and 0.8% [0.6%, 1.1%] for CCT, nasal PCT, and temporal PCT, respectively. There was an inverse relationship between temporal Dk/t and %ΔPCT (p

SIGNIFICANCE:Identification of the association of specific signs of dry eye disease with specific visual function deficits may allow for more targeted approaches to treatment. PURPOSE:The purpose of this study was to explore the association of dry eye signs and symptoms with visual acuity (VA) and contrast sensitivity in the Dry Eye Assessment and Management study. METHODS:Baseline data from participants in the Dry Eye Assessment and Management study were used in this secondary cross-sectional analysis. Standardized procedures were used to obtain results on the Ocular Surface Disease Index (OSDI), high-contrast logMAR VA, contrast sensitivity, tear film debris, tear breakup time (TBUT), corneal fluorescein staining, meibomian gland evaluation, conjunctival lissamine green staining, and Schirmer test scores. Generalized linear models that included age, refractive error status, and cataract status were used to assess the association between VA and contrast sensitivity with OSDI score and each dry eye sign. The Hochberg procedure was used to account for multiple comparisons. RESULTS:Among 487 participants (974 eyes), worse VA was associated with worse mean score on the OSDI vision subscale (39.4 for VA 20/32 or worse vs. 32.4 for VA 20/16 or better; adjusted linear trend, P = .02); scores were not associated with contrast sensitivity. Severe meibomian gland plugging and abnormal secretions were associated with worse mean log contrast sensitivity (1.48 for severe vs. 1.54 for not plugged [P = .04] and 1.49 for obstructed vs. 1.57 for clear [P = .002], respectively). Longer TBUT was associated with better mean log contrast sensitivity (1.57 for TBUT >5 seconds and 1.51 for TBUT ≤2 seconds, P < .0001). CONCLUSIONS:Worse VA rather than worse contrast sensitivity drives vision-related symptoms in dry eye. Greater tear film instability was associated with worse contrast sensitivity.

PurposeMeibomian gland contrast may be a potential indicator of gland health, especially among isotretinoin users. We aimed to develop a repeatable and reliable method for measuring Meibomian gland contrast from meibography images.MethodsLower lid (LL) and upper lid (UL) meibography were captured with the OCULUS Keratograph 5M (OCULUS, Inc) at 2 visits under the following 4 conditions: face centered with room lights on (C), left-turned face (L), right-turned face (R), and face centered with room lights off (CLO). Contrast was measured with Fiji (v2.0.0-rc-59). Coefficient of repeatability and limits of agreement (LOA) were determined using Bland-Altman plots.ResultsA total of 512 meibography images from 16 subjects (age ± SD = 24.8 ± 5.2 years; 13 female patients) were collected. Coefficient of repeatability between visits was 10.5 for UL and 14.9 for LL. Lower and upper LOA, respectively, for UL, compared with condition C, were -10.9 [95% confidence interval (CI), -13.5 to -8.3] and 6.2 (95% CI, 3.6-8.8) for L; -11.0 (95% CI, -13.8 to -8.1) and 7.0 (95% CI, 4.2-9.8) for R; and -9.0 (95% CI, -11.6 to -6.5) and 7.2 (95% CI, 4.7-9.8) for CLO. Lower and upper LOA, respectively, for LL, compared with condition C, were -18.1 (95% CI, -22.6 to -13.5) and 11.0 (95% CI, 6.5-15.5) for L; -15.3 (95% CI, -19.2 to -11.3) and 9.9 (95% CI, 6.0-13.9) for R; and -12.0 (95% CI, -15.1 to -8.8) and 8.2 (95% CI, 5.0-11.3) for CLO.ConclusionsMeibomian gland contrast is a repeatable and reliable measure for changes in Meibomian gland contrast greater than 11 in the UL and 18 in the LL.

PURPOSE:To evaluate post-lens tear dynamics at two different time points during scleral lens wear in two cohorts with 10 neophytes each. METHODS:All subjects wore bilaterally scleral lenses for 5 h on 3 separate visits. Post-lens tear exchange was measured using Out-in method, which required 5 μL of 2% FITC-Dextran instilled on the bulbar conjunctiva during lens wear. Time taken to observe the first sign of fluorescence in post-lens tear reservoir was recorded with a stopwatch. Out-in measurements were collected at 5-hour  post-lens insertion in Group 1 and compared with those obtained at 20 min of lens wear in Group 2. Tear dynamics under the lens was observed in Group 2 with fluorogram using a modified slit-lamp technique (Tan et al., 2018) to monitor post-lens fluorescence intensity and with high-resolution spectral domain optical coherence tomography (ENVISU 2300; Bioptigen Inc.) to measure post-lens tear thickness (PoLTT) over 5 h of lens wear. RESULTS:60% of subjects in Group 1 achieved Out-in times less than 5 min at 5-hour post-lens insertion, compared with 67% of subjects at 20-min lens wear (Tan et al., 2018). Using qualitative analysis on 60 series of data in Group 2 to compare the changes in fluorescence intensity and PoLTT with respect to lens-wearing time, 27% was due to lens settling, 13% was due to tear exchange and mixing while 60% indicated tear dynamics under scleral lenses was due to a combination of tear exchange, mixing, and lens settling. CONCLUSION:Tear flow into tear reservoir under a scleral lens on subjects with healthy cornea occurred at 20 min and 5 h after lens insertion. After 5 h of lens wear, roughly one third of the subjects had no tear flow into post-lens reservoir, as the observed decline in post-lens tear fluorescence was predominately due to lens settling.

To quantify corneoscleral junction (CSJ) topography in soft contact lens (SCL) wearers, and assess the association between the CSJ and SCL performance and subjective comfort, forty-four adapted SCL wearers (16 Asians, 16 Caucasians, 12 Latinos) were recruited for the present study. Corneal topography was taken with a Medmont E300 (Medmont International, Pty Ltd.). CSJ images were taken with a commercial OCT (Bioptigen, Inc.). Our published CSJ image analysis technique was used to describe the geometric properties of the CSJ using the sum of squared orthogonalized residuals (SSRo). Multivariable mixed effects models were employed to examine associations between SSRo and subject demographics, ocular characteristics, SCL fit and performance, and comfort. The SSRo was significantly related to quadrant (p

PurposeTo evaluate the prevalence of novel candidate Sjogren syndrome (SS) autoantibodies [salivary protein-1 (SP-1), parotid secretory protein, carbonic anhydrase 6] in the DRy Eye Assessment and Management (DREAM) cohort, a study evaluating the effectiveness of omega-3 fatty acid supplements for the treatment of dry eye.MethodsParticipants underwent ocular surface examinations and serological testing for traditional and novel SS autoantibodies. Dry eye assessment and management participants were categorized into the following 3 groups: 1) no history of SS or other autoimmune diseases and negative traditional SS autoantibodies (n = 352); 2) no history of SS but a history of other autoimmune diseases (n = 66); and 3) those who met the 2012 American College of Rheumatology SS classification criteria (n = 52).ResultsEleven percent had a history of SS, and 6% of those without a history of SS most likely had undiagnosed SS. The SS group had a higher prevalence of SP-1 autoantibodies than the group without SS or other autoimmune diseases (33% vs. 19%; P = 0.02) but had no difference in carbonic anhydrase 6 (P = 0.31) or parotid secretory protein autoantibodies (P = 0.33). Participants who were positive for the traditional autoantibodies alone or positive for both traditional and novel autoantibodies had the highest scores for corneal (P = 0.002) and conjunctival staining (P < 0.001).ConclusionsData from this multicenter, prospective study demonstrated that one of the novel candidate autoantibodies, SP-1, is associated with underlying SS and that novel autoantibodies may be associated with worse ocular surface disease. Future longitudinal studies are needed to evaluate their utility in screening patients with dry eye for SS.

SignificanceThe present study with small-diameter scleral lenses (SLs) revealed that post-lens tear thickness (PoLTT) was significantly associated with post-lens tear mixing, but not with central corneal edema, after short-term SL wear.PurposeThe aim of this study was to investigate the influence of SL tear clearance (PoLTT) on central corneal thickness and post-lens tear dynamics during 5-hour lens wear.MethodsNeophytes with no active ocular disease were fitted bilaterally with SLs (hofocon A; 15.6-mm diameter; ~438-μm thickness; 97 Dk; 1.44 refractive index) with various initial PoLTT values ranging from 74 to 543 μm. Central corneal thickness and PoLTT were measured using optical coherence tomography during lens wear. Tear mixing was assessed using fluorogram and "out-in" method.ResultsThe mean central corneal edema after 5-hour lens wear was 1.51% (95% confidence interval, 1.26 to 1.76%; P < .001), reached its peak at 2-hour post-lens insertion (1.65% [95% confidence interval, 1.45 to 1.85%]), and was independent of PoLTT. The fastest fluorescence decay of the post-lens tear film was observed superiorly. The fluorescence decay rate increased from center to periphery in all quadrants except superiorly. An inverse relationship was found between PoLTT and fluorescence decay rate at both 20-minute and 5-hour wear after lens insertion (P < .05). Excluding observations with out-in time exceeding 5 minutes, we found a direct relationship between PoLTT at 20 minutes after lens insertion and out-in time (P = .047). The % change in the PoLTT after 5-hour wear was greater with a thinner initial tear clearance than those with a thicker one (P = .034).ConclusionsWithin our study parameters, a thinner PoLTT under a small-diameter SL was associated with faster PoLTT mixing. However, there was no relationship between PoLTT and central corneal thickness during 5-hour SL wear.

BackgroundDry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms.MethodsIn a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs.ResultsA total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups.ConclusionsAmong patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

BackgroundDry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms.MethodsIn a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs.ResultsA total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups.ConclusionsAmong patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

Purpose:There has been interest in determining whether lid wiper epitheliopathy (LWE) plays a key role in causing ocular discomfort. Conflicting reports have made it difficult to discern whether LWE is more prevalent in certain populations, what characteristics are associated with its severity, and what its role is in symptomology. This cross-sectional study on a large and diverse population attempts to answer these questions. Methods:Subjects were asked to complete questionnaires related to dry eye and to ocular discomfort. A comprehensive set of ocular surface parameters were assessed, including LWE length and width, tear-film lipid layer thickness, fluorescein tear breakup time (FTBUT), lid-parallel conjunctival folds (LIPCOF), and corneal staining. Results:A total of 287 subjects participated in the study. LWE was observed in 45% of the study cohort and was twice as prevalent in Asians than non-Asians (P < 0.005). LWE was more likely to present in contact lens wearers than non-contact lens wearers (P = 0.03). Decreased FTBUT was associated with increased LWE length and width (P < 0.005 and P = 0.01, respectively), although only a small effect size was noted. Presence of LIPCOF was linked with a 0.25-grade increase in LWE width (P = 0.01). Only LWE width was associated with greater symptoms in contact lens wearers. Conclusions:LWE was associated with decreased tear-film stability, contact lens wear, lid anatomy, and LIPCOF. LWE was not associated with symptoms in non-contact lens wearers. LWE width was associated with greater symptoms in contact lens wearers but was only clinically significant with moderate to severe LWE width.

SignificanceA simple methodology is presented to quantify basal tear production with a modified Schirmer-tear test.PurposeWe introduce a simple clinical procedure to measure quantitative basal tear-production flowrates, QL, from a modified Schirmer-tear test (STT).MethodsEight healthy subjects aged at least 18 years underwent modified STTs on both eyes for two visits each. Schirmer strips were sheathed with transparent tape before insertion. Topical anesthetic minimized reflex tearing. Wetting lengths were measured every 30 s for 5 min; QL was calculated from the linear slope of wetting length versus time. Determination of QL requires mass-balance equations on the tear prism and Schirmer strip with strip imbibition kinetics obeying Darcy and Young-Laplace laws.ResultsBasal tear production rates varied from essentially 0 to about 2 μl/min. With some exceptions, right and left eyes showed similar tear production rates.ConclusionsBy following the modified STT, QL is established with minimal additional effort over a standard Schirmer test. We predict and observe four different subtypes of imbibition kinetics depending on how short or long the time is for first appearance of the wetting front and on how fast or slow is tear production. For slow lacrimal production rates, the standard 5-min wetting length does not correlate with basal tear production.

PurposeIn this article, we introduce a novel flow chart-based screening tool for the categorization of contact lens-induced dryness (CLIDE) and its impact on daily visual activities: the Berkeley Dry Eye Flow Chart (DEFC).MethodsOne hundred thirty (130) experienced soft contact lens wearers discontinued lens wear for 24 hrs, passed a baseline screening and eye health examination, completed the Ocular Surface Disease Index (OSDI) then were dispensed fresh pairs of their habitual lenses. After 6 hrs of wear, subjects were administered a battery of symptom questionnaires, and underwent non-invasive tear breakup time (NITBUT) measurement, grading of distortion in reflected topographer mires, grading of lens surface wettability, and a fluorescein examination of the ocular surface. Subjects returned after at least 48 hrs and repeated all assessments after 6 hrs of wear of a second fresh pair of habitual lenses.ResultsThe repeatability of the DEFC between visits was within 1%, and Limits of Agreement and Coefficient of Repeatability were comparable to those of the other CLIDE assessments. Higher DEFC score was significantly related to shorter pre-lens NITBUT, higher OSDI score, and higher Visual Analog Scale (VAS) ratings of average and end-of-day severity and frequency of dryness (all p < 0.001). For CLIDE as diagnosed based on DEFC score, the highest sensitivities and specificities were achieved by the OSDI and VAS ratings; pre-lens NITBUT exhibited good sensitivity but poor specificity. The optimum pre-lens NITBUT diagnostic threshold was found to be ≤ 2.0 sec for debilitating CLIDE, and the OSDI threshold was ≥ 11.4.ConclusionsThe DEFC provides a means of quickly categorizing CLIDE patients based on severity and frequency of symptoms, and on the degree to which symptoms impact daily life. The DEFC has several potential advantages as a CLIDE screening and monitoring tool, has good repeatability, and is significantly related to commonly employed clinical assessments for CLIDE.

PurposePain sensitivity has been identified as a factor that affects how individuals answer dry eye questionnaires, but it is unknown how it affects ocular discomfort. This study used the time that individuals could refrain from blinking as an indicator of ocular discomfort and set out to determine whether it was related to pain sensitivity, while adjusting for ocular surface conditions.MethodsSubjects first completed the Pain Sensitivity Questionnaire to quantify pain sensitivity levels. Exposed interpalpebral area, tear meniscus height, tear-film lipid layer thickness, ocular surface cooling, and noninvasive tear breakup were assessed. Subjects were then asked to refrain from blinking until the initial onset of discomfort, which was termed "the maximum interblink period" (MIBP), while ocular surface cooling rate was simultaneously measured. Subjects were seen for four visits over a course of 2 days.ResultsForty-two subjects (36 females, 6 males) completed the study, with a mean (SD) age of 23.2 (3.8) years. A longer MIBP was associated with decreased pain sensitivity (P = 0.04), lower ocular surface cooling rate (P < 0.001), and Asian ethnicity (P = 0.005). Based on the results from the mixed-effect model, it is estimated that individuals would be able to refrain from blinking for an additional 4 seconds if they had the lowest (0.6) compared to the highest (6.1) pain sensitivity in the study cohort.ConclusionsThe Pain Sensitivity Questionnaire was associated with the MIBP length even after adjusting for ocular surface conditions, which suggests that pain sensitivity plays a role in influencing how ocular discomfort is perceived.

SignificanceLens care multipurpose solutions (MPSs) can have varying effects on contact lens (CL) surface properties and the corneal epithelium.PurposeThe aim of this study was to investigate the short-term effects of newer MPS on CL comfort and dryness, prelens tear-film stability, and ocular-surface health. In vitro study was also performed to assess the effect of MPSs on CL surface properties.MethodsAcuvue 2 CLs were soaked in control solution, Clear Care (CC), or test solutions: PureMoist, Biotrue, RevitaLens (RL), or saline solution (SS). Over four visits, subjects were exposed to control solution in one eye and to test solution in the contralateral eye for 2 hours using presoaked CLs. Contact lens comfort and dryness, ocular-surface health assessment, prelens noninvasive tear breakup time, and corneal epithelial permeability measured with fluorometry were assessed. Captive-sessile bubble technique evaluated CL wettability and viscous drag in vitro.ResultsAt 10 minutes, mean comfort ± SD with PureMoist (76 ± 22) was lower than CC (86 ± 15, P = .02), Biotrue (92 ± 9, P < .005), RL (90 ± 13, P < .005), and SS (90 ± 14, P < .005). No other difference in comfort or dryness was noted. RevitaLens was associated with greater corneal epithelial permeability than CC (P = .020) and increased corneal staining compared with all MPSs (P < .005 for all). RevitaLens was also associated with longer prelens noninvasive tear breakup than CC (P < .005). In vitro results agreed with clinical findings of tear-film stability as RL reduced viscous drag. Contact lens surface wettability was enhanced by all MPSs in comparison to SS.ConclusionsDifferences of MPSs on the ocular surface were found in vivo and in vitro. RL caused the greatest corneal epithelium disruption but also associated with higher tear-film stability. The effect of MPSs on CL surface properties in vitro seems to reflect how MPSs altered prelens tear stability.

PurposeAssess potential risk factors for severe Meibomian gland atrophy (SMGA) in a young adult population.MethodsCross-sectional study using medical history and ocular surface examination to evaluate relationships with study outcomes: SMGA, tear lipid layer (TLL) thickness, non-invasive (NITBUT) and fluorescein (FTBUT) tear breakup times, and symptoms using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire.ResultsOne hundred one participants (101; 202 eyes; Age: mean±SD = 22.3±4.0 years) completed the study. Hormonal birth control (HBC) use was the only significant risk factor for SMGA (p = 0.028). Female HBC users had 4.8 times greater odds of having SMGA compared to female HBC non-users (p = 0.028), but the odds of having SMGA was similar between female HBC non-users and males (p = 0.885). Multivariable analysis suggested that the relationship between SMGA and TLL thickness was dependent on HBC use. Compared to female HBC non-users without SMGA, TLL thickness for HBC users was estimated to be 10 nm thinner if SMGA was absent (p = 0.007) and 21 nm thinner if SMGA was present (p

PurposeDirectional Optical Coherence Tomography (D-OCT) is a method used to optically segment and identify the outer nuclear layer (ONL) in vivo. The purpose of this study was to determine the repeatability and reproducibility of D-OCT ONL thickness measurements in healthy eyes.MethodsSixteen healthy eyes of sixteen subjects were imaged using the Cirrus SD-OCT. The OCT beam entry position was varied horizontally and vertically through the pupil, and cross-sectional images were obtained at baseline and 1-month follow-up by two observers. Detailed segmentation was performed to quantify the thickness of ONL without the inclusion of overlying Henle Fiber Layer. Inter-observer, intra-observer, and inter-visit variability was evaluated using Bland-Altman and coefficient of variation analysis for each category.ResultsAll 16 eyes were successfully imaged, registered, and segmented. The maximum mean (SD) inter-operator difference was 2.6 (4.8) μm. The maximum mean (SD) intra-operator difference was 2.4 (5.3) μm. There was no statistically significant difference in ONL measurements detected between baseline and follow-up (p > 0.05). The mean (SD) differences measured across visits by one operator varied from -1.6 (3.1) to 1.1 (6.1) μm. The mean (SD) coefficient of variance (CV%) for all sectors with horizontal orientation was 9.1% (2.3%), 10.1% (2.5%), and 8.6% (2.3%) for inter-observer, intra-observer, and inter-visit, respectively. The mean (SD) coefficient of variance (CV%) for all sectors with vertical orientation was 8.3% (1.8%), 6.9% (1.4%), and 8.3% (2.1%) for inter-observer, intra-observer, and inter-visit, respectively. The majority of the variation of paired repeated measurements originated from between-subject variance. The within-subject variance accounted for less than 1% of the total variability.ConclusionsONL thickness measurements can be quantified with good repeatability and reproducibility using D-OCT. Identifying the magnitude of D-OCT variability among normal subjects will allow for improved development of future clinical studies that quantitatively track the progression of macular pathology.

PurposeTo utilize the Pain Sensitivity Questionnaire (PSQ) to assess the influence of pain sensitivity on perceptions of ocular discomfort and dryness.MethodsSubjects completed a battery of questionnaires, including history of ocular and general health, contact lens wear history, the Ocular Surface Disease Index (OSDI) questionnaire, visual analog scale (VAS) 100-point rating scales to assess severity and frequency of average and end of day (EOD) discomfort and dryness, and the PSQ to assess pain sensitivity level. Masked subjects were then instructed to wear one inverted and one normally oriented soft contact lens contralaterally for 30 minutes to induce an inter-eye difference in comfort and dryness sensations. Subjects rated comfort and dryness in each eye on VAS every 5 minutes during contact lens wear. A slit lamp examination was performed to evaluate ocular surface health and to assess contact lens fit.ResultsOne hundred and fifty-three subjects (111 females, 42 males) completed the study. In separate models, a higher PSQ score was significantly associated with higher OSDI score (p = 0.002), lower average and EOD comfort (p = 0.005 and 0.001, respectively), and greater EOD dryness (p = 0.04). The minimum (0.14) and maximum (7.14) PSQ scores observed in our subject cohort (i.e., from the subjects who were the least and most sensitive to pain, respectively) corresponded to an estimated difference of 11 points on the OSDI, 20 points on the VAS scale for average comfort, 31 points for EOD comfort and 17 points for EOD dryness. In a mixed effects model, a higher PSQ score was significantly associated with a greater inter-eye difference in comfort (p = 0.013) and dryness (p = 0.010) during CL wear.ConclusionsPain sensitivity influences perceptions of ocular discomfort and dryness, and should be taken into account when evaluating subjective assessments of these symptoms.

A panel of experts was invited to discuss the following questions: Why does the prevalence of dry eye disease (DED) appear to be increasing? Are you satisfied with the current definition and classification of DED-aqueous deficiency versus evaporative dry eye? Beyond the innate human factors (e.g., genetics), what external factors might contribute to DED? What areas related to DED need to be more fully understood? In examining a patient complaining of dry eye, what is your strategy (e.g., tests, questionnaire)? What is your strategy in unraveling the root cause of a patient's dry eye symptoms that may be shared by many anterior segment diseases? What are the two or three most common errors made by clinicians in diagnosing DED? Why do contact lens (CL) patients complain of dry eye while wearing lenses but not when not wearing lenses? What areas related to CL discomfort need to be more fully understood? What is your most effective strategy for minimizing CL discomfort? With current advances in biotechnology in dry eye diagnostics and management tools, do you think our clinicians are better prepared to diagnose and treat this chronic condition than they were 5 or 10 years ago? Do you foresee any of these new point-of-care tests becoming standard clinical tests in ocular surface evaluation? What treatments are effective for obstructed Meibomian glands secondary to lid margin keratinization? What level of DED would prevent you from recommending an elected ophthalmic surgery? What strategy do you use to help your patients comply with the recommended home therapies? How do you best manage patients whose severity of dry eye symptoms does not necessarily match clinical test results, especially in cases of ocular surface neuropathy? Where do you see dry eye diagnosis and treatment in 10 years or more?

PurposeTo examine the relationships among tear osmolarity, tear film stability, and several measures of dry eye (DE) symptoms in a multivariable analysis.MethodsA cross-sectional study was conducted with 137 subjects (68 non-contact lens [CL] wearers and 69 soft CL wearers) recruited from a university campus. Tear breakup time (TBUT) was measured noninvasively (NITBUT) and with fluorescein (FTBUT). Tear osmolarity was measured by an osmometer. Dry eye symptoms were assessed using the Dry Eye Flow Chart and several different questionnaires.ResultsSubjects ranged in age from 18 to 67 years, with a mean of 28 years. Subjects had a mean (SD) osmolarity of 293 (10) mOsm/L, NITBUT of 14.1 (10.9) seconds, and FTBUT of 14.8 (12.6) seconds. Shorter NITBUT and FTBUT were significantly associated with female sex (p = 0.001 and p = 0.027, respectively) and Asian ethnicity (p = 0.030 and p = 0.004, respectively). There were no clinically significant relationships between tear osmolarity and FTBUT, NITBUT, or DE symptoms. Higher Dry Eye Flow Chart score (i.e., worse symptoms) was associated with older age (p < 0.001), female sex (p = 0.014), CL wear (p < 0.001), shorter NITBUT (p < 0.001), and shorter FTBUT (p = 0.028). The sensitivities and specificities for using clinical measurements to diagnose moderate to severe DE were as follows: osmolarity, 0.67 and 0.46, respectively; NITBUT, 0.72 and 0.52, respectively; and FTBUT, 0.68 and 0.57, respectively.ConclusionsIn a population of asymptomatic, mild and moderate DE patients, increased tear osmolarity was not significantly associated with reported symptom severity and frequency. Tear osmolarity, NITBUT, and FTBUT exhibited similar sensitivities and specificities when used to diagnose moderate to severe DE.

PurposeTo determine associations for contact lenses (CLs) and meibomian gland atrophy in a matched-pair study.MethodsContact 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.ResultsA 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).ConclusionsThis study determined inconclusive associations with CLs and meibomian gland atrophy. This study also provided a comprehensive assessment of differences between CL and NCL wearers.

PurposeTo investigate the relationship between ocular surface temperature (OST) and tear film thinning and breakup.MethodsSimultaneous imaging of OST and fluorescein tear thinning and breakup (FTBU) was performed on 20 subjects. Subjects were asked to open their eyes and refrain from blinking for as long as they could during testing. Ocular surface temperature was measured using an infrared thermographic camera (FLIR A655sc) and rates of ocular surface cooling (OSC) were analyzed using commercially available software. A method was developed to quantify the rate of FTBU formation using image-processing software.ResultsAreas of FTBU and regions of OSC were observed to be colocalized, with localized cooling preceding the formation of FTBU. The rates of OSC and FTBU formation were positively correlated (r = 0.74). A second-order polynomial model accurately describes the physiological relationship between the area of FTBU and OST (p < 0.001). A linear approximation provides a more clinically interpretable rate of FTBU formation with decreasing OST (p < 0.001), while still retaining high R.ConclusionsThe results suggest a direct relationship between FTBU formation and OSC. That cooling of the ocular surface precedes FTBU formation implies a process of evaporation contributing to tear film thinning and breakup. Our study suggests that measuring the OSC rate could be an indirect assessment of tear evaporation and could contribute to the management of evaporative dry eye.

PurposeTo identify patient characteristics at a baseline ocular surface evaluation that correlate with improvement in dry eye symptoms at a follow-up visit after treatment with the LipiFlow Thermal Pulsation System.MethodsThirty-two patients completed a comprehensive baseline ocular surface evaluation and were treated with the LipiFlow Thermal Pulsation System followed by maintenance home therapy. Lipid layer thickness and blink pattern were determined using the LipiView Interferometer. Noninvasive tear breakup time was measured using a Medmont E300 Corneal Topographer. Slit lamp biomicroscopy was used to evaluate invasive tear breakup time and corneal staining after instillation of fluorescein dye. Conjunctival staining, location of the line of Marx, and presence of lid wiper epitheliopathy were evaluated with lissamine green dye. Meibomian gland expressibility was scored using the TearScience Meibomian Gland Evaluator, and meibography was imaged using the Oculus Keratograph. A logistic regression model was used to estimate the odds ratios for having a decreased posttreatment score (reduced symptoms) of Standard Patient Evaluation of Eye Dryness (SPEED).ResultsBaseline SPEED score (p = 0.01) and sex (p = 0.03) had significant odds ratios at the α = 0.05 level. Baseline noninvasive tear breakup time (p = 0.07), number of grade 0 meibomian glands in the lower lid (p = 0.09), and conjunctival staining grade in the inferior region (p = 0.10) met an α = 0.10 criterion for significant odds ratios, but not the typical α = 0.05 criterion. Higher baseline SPEED score and male sex had greater odds for decreased posttreatment SPEED score.ConclusionsOur results identified factors that better select candidates for LipiFlow Thermal Pulsation System.

Purpose: To evaluate the influence of lens care solutions (LCS) on interfacial dynamics and rheological properties of human tear-lipid films. Methods: Tear lipids were extracted from Schirmer strips collected from 6 healthy subjects. Sessile bubble tensiometry was used to study interfacial properties at 22. °C. Lipids were deposited on an air bubble immersed into electrolytes solution to form 90. ±. 20. nm films. Lipid films were subjected to expansion-compression cycles for dynamic interfacial properties and to step-strain relaxations for assessments of rheological properties. LCS (BioTrue [BT], PureMoist [PM], Revitalens [RL], ClearCare [CC]) were injected into optical chamber and equilibrated for 2. h without or with lipid films. Dynamic interfacial properties of films were measured. Then electrolyte solution was pumped through chamber and properties of films were re-evaluated. Results: Equilibrium surface tension (EST), elasticity modulus ( E), and relaxation times ( τ) of tear lipids were 22. ±. 2.1. mN/m, 10.7-14.8. mN/m, and 80-150. s, respectively. EST for LCS was 45.3. ±. 0.8 for CC, 40.3. ±. 0.8 for BT, 33.4. ±. 1.0 for PM, and 30.1. ±. 0.8. mN/m for RL. E for LCS varied within 0.5-6.7. mN/m, and τ varied from 49 to 68. ±. 5. s. For mixed lipids. +. LCS films, EST remained unchanged whereas E and τ were reduced for all LCS types. Exposure to PM and RL noticeably altered the shape of lipid-film iso-cycles. These changes persisted after LCS washout. Conclusions: Some components of LCS bind irreversibly to lipid films and make them less viscous and less elastic. These findings suggest the possibility of tear-film destabilization upon LCS exposure. © 2014.

PurposeTo investigate factors of ethnicity, sex, age, and diurnal variation on human corneal epithelial permeability.MethodsData of corneal epithelial permeability to sodium fluorescein (Pdc) were collected from 374 noncontact lens wearers at various times after awakening throughout the day. Mixed-effect models were developed to investigate the association between Pdc and factors of interest, including time awake (TA), age, sex, ethnicity, and interactions of these factors.ResultsTwo models evaluated the "Pdc recovery period" from awakening to 2 hours (Model 1) and the "Pdc plateau" period after TA of 2 hours (Model 2). In Model 1, Pdc declined significantly with length of awake time (P = 0.000), and showed higher Pdc with males (P = 0.098), although this sex difference was not observed after 2 hours (Model 2). Both models showed significantly higher Pdc in Asians than in non-Asians (P = 0.000) and increased Pdc with age (P = 0.048, P = 0.001).ConclusionsBaseline corneal epithelial barrier function increases after overnight sleep and varies significantly by ethnicity and age.

ObjectivesTo determine whether Asian and white subjects differ in clinical signs or subjective symptoms in response to the use of different biguanide-preserved contact lens care solutions.MethodsForty-two subjects (15 Asian and 27 white) wearing lotrafilcon B silicone hydrogel contact lenses used a preservative-free lens care solution bilaterally for 2 weeks, then used two biguanide-preserved solutions (solution 1: ReNu MPS; solution 2: AQuify MPS) contralaterally in randomly assigned eyes for 4 weeks. Comprehensive ocular surface examinations were performed and symptomatology questionnaires were administered every 2 weeks. Investigators were masked as to solution assignment during examinations, whereas subjects were not to avoid potential difficulties in compliance with the protocol.ResultsWith solution 1, most Asian and white subjects had grade 2 or greater corneal staining after 2 weeks (67% and 59%, respectively) and 4 weeks (60% and 67%, respectively). With solution 2, grade 2 or greater corneal staining occurred in 40% of Asians after 2 weeks and in 13% after 4 weeks, but in only 4% of whites after 2 weeks and 0% after 4 weeks. Whites reported significantly better average comfort (P=0.046) and less dryness (P

PurposeTo develop and test a novel quantitative method of describing the corneoscleral junction, including metrics that reflect both the angle and the topography in this region of the ocular surface.MethodsForty-eight neophyte subjects were recruited (16 Asian, 16 white, and 16 Latino). Optical coherence tomography images of the nasal, temporal, superior, and inferior quadrants in both eyes were taken. Custom image analysis software was written in Matlab to allow the observer to select a point defining the center of the junction, from which 20 concentric circles were automatically drawn. The surface of the junction in the image was automatically located by edge-detection routines, and the circles intersecting this edge defined a series of points in the Cartesian plane. A linear regression was fit to these points, and a set of metrics based on the regression residuals was calculated.ResultsThe sum of the squared orthogonalized residuals (SSRo) was the most repeatable metric and had the advantage of being unaffected by the orientation of the image. The SSRo was significantly greater in the nasal quadrant (p < 0.001), reflecting a more pronounced angle and/or rougher surface. The flattest and smoothest topography was found in the temporal quadrant. Whites had significantly higher SSRo than Asians and Latinos (p < 0.001).ConclusionsThis study presents a novel metric for characterizing the angle and topography of the corneoscleral junction using optical coherence tomography and establishes differences among quadrants and between ethnic groups.

PurposeTo determine whether daily irrigation with sterile saline solution during silicone hydrogel (SiH) contact lens continuous wear (CW) can mitigate increases in corneal epithelial permeability (Pdc) and reduce the risk of adverse events.MethodsIn this study, 161 non-contact lens wearers were fit with SiH contact lenses and randomized to either a treatment (n = 81) or control (n = 80) group for 30-day CW. Subjects in the treatment group irrigated every morning and whenever dryness symptoms occurred; subjects in the control group did not. Mixed effects models were employed to assess the changes in Pdc, and survival analysis methods were employed to estimate the risk for adverse events.ResultsEpithelial permeability increased over 30-day CW with SiH lenses (P = 0.001). Risk of inflammatory (odds ratio [OR] = 1.94) and lens-induced (OR = 1.90) adverse events increased with irrigation; these events also occurred sooner, on average, in the irrigation group. Although the overall risk for Asians was higher than for non-Asians, irrigation had no significant impact on risk among Asians, but significantly increased risk among non-Asians.ConclusionsThirty-day CW results in a measurable increase in epithelial permeability. Risk of inflammatory and lens-induced adverse events also increase over time during CW. Daily irrigation with sterile saline solution did not mitigate increases in epithelial permeability or decrease risk of adverse events.

PurposeThis study aimed to examine the effects of demographic, lens performance, and ocular surface response measures on contact lens-related discomfort and dryness, using a large contact lens study database.MethodsA total of 4164 records were extracted from a database of 220 subjects participating in 46 silicone hydrogel contact lens studies. Subjects discontinued lens wear for 24 hours and were then fit with either comfilcon A or enfilcon A lenses. The fit and performance of the lenses, along with subjective comfort and dryness, were assessed on insertion and after 3 and 6 hours of wear. After 6 hours of wear, ocular surface health was also assessed by fluorescein slitlamp examination.ResultsDecreased comfort at 3 hours after insertion was associated with excessive lens movement (p < 0.001), front surface deposits (p = 0.004), poor wettability (p = 0.014), and Asian ethnicity (p < 0.001). After 6 hours of wear, decreased comfort remained associated with greater lens movement (p = 0.032) and Asian ethnicity (p < 0.001), along with inferior corneal staining (p < 0.001). Dryness after 3 hours of wear was associated with greater lens movement (p < 0.001), Asian ethnicity (p < 0.001), increased deposits (p < 0.001), and poor wettability (p < 0.001). Dryness after 6 hours of wear remained associated with greater lens movement (p < 0.001) and Asian ethnicity (p < 0.001), along with inferior corneal staining (p < 0.001) and inferior lens decentration (p = 0.001).ConclusionsExcessive lens movement, inferior lens decentration, poor surface wettability and deposits, inferior corneal staining, and Asian ethnicity are associated with discomfort and dryness. Clinicians should consider all these factors to achieve the most comfortable and successful contact lens fit.

PurposeTo explore interfacial behaviors and effects of temperature and dilatation on dynamic properties of multilayered human tear lipids extracted from silicone hydrogel (SiH) lenses worn by asymptomatic Asian and white subjects.MethodsInterfacial properties of lipids extracted from Focus N&D lenses worn by 14 subjects continuously for 1 month were studied. The lipids were deposited on an air bubble immersed in a model tear electrolyte (MTE) solution to form 100 ± 20-nm-thick films. Surface pressure was recorded during slow expansion/contraction cycles to evaluate compressibility and hysteresis of lipid films. Films were also subjected to fast step-strain dilatations at temperatures of 22 to 45°C for their viscoelastic property assessment.ResultsIsocycles for Asian and white lipids were similar at low surface pressures but had distinctly different compressibility and hysteresis at dynamic pressures exceeding 30 mN/m. Rheological parameters of reconstituted lipids were also dissimilar between Asian and white. The elastic modulus E∞ for white lipids was 1.5 times higher than that for Asian lipids, whereas relaxation time (t) was on average 1.3 times higher for Asian. No significant changes were observed in rheological properties of both Asian and white lipids when temperature increased from 22.0 to 36.5°C. However, for white lipids, E∞ reduced considerably at temperatures higher than 42.0°C, whereas t remained unchanged. For Asian lipids, both E∞ and t started to decline as temperature increased to 38°C and higher.ConclusionsHigher elastic modulus of white lipids and elasticity threshold at certain deformations indicate stronger structure and intermolecular interactions as compared with more viscous Asian lipids. The differences in interfacial behaviors between Asian and white lipids may be associated with the differences in their chemical compositions.

PurposeTo explore the relationships among length of contact lens (CL) wear, degree of corneal staining and severity of dryness symptoms, and to determine whether these relationships differ between Asians and non-Asians.MethodsAdapted soft CL wearers (n=395; 180 Asian, 215 non-Asian) were required to discontinue CL wear for at least 24h and report to the University of California, Berkeley Clinical Research Center (UCB-CRC). Fluorescein corneal staining was graded according to Brien Holden Vision Institute scales. Length of CL wear was reported by subjects and subjective dryness ratings were collected using the UCB-CRC Dry Eye Flow Chart (DEFC).ResultsMore Asian CL wearers exhibited corneal staining compared to non-Asians, and Asian CL wearers had a higher mean grade of corneal staining (p

PurposeTo ascertain whether a difference in the permeability of the corneal epithelium to fluorescein (Pdc) exists between Asians and non-Asians.MethodsFrom a multi-study database we extracted 632 records of baseline, open-eye Pdc measurements taken on both eyes of 176 subjects. Subjects were awake for a minimum of 4h before measurement, and were free of ocular disease and central corneal staining. Pdc was transformed by natural logarithm to better approximate normality for statistical tests.ResultsThe mean ln(Pdc) in the Asian group was significantly greater than in the non-Asian group [-2.34 ln(nm/s) vs. -2.58 ln(nm/s); p

PurposeTo identify the diurnal variations of tear osmolarity (TO) and its relationship with central corneal thickness (CCT) and corneal deswelling over a 14-hour period.MethodsTO and CCT were measured using the TearLab Osmometer and Bioptigen spectral domain optical coherence tomography, respectively, on 38 healthy neophytes (mean age, 21.5 ± 2.2 years). TO and CCT were measured at bedtime (baseline), upon awakening, 20 minutes, 40 minutes, 1 hour, 2 hours, 4 hours, and 8 hours after awakening. Deswelling rate was estimated and expressed as percent recovery per hour (PRPH). Mixed-effect linear regression models describe the relationships among TO, CCT, and PRPH.ResultsThe tear film upon wakening (264 ± 14 mOsm/L) was hypoosmotic compared with baseline (297 ± 15 mOsm/L, P < 0.001). TO (in mOsm/L) at 20 minutes, 40 minutes, 1 hour, 2 hours, 4 hours, and 8 hours were 287 ± 10, 292 ± 16, 293 ± 12, 292 ± 10, 289 ± 10, and 286 ± 10, respectively. CCT (mean ± SD) at baseline was 552.2 ± 35.9 µm and increased to 572.0 ± 38.7 µm after sleep. CCT returned to baseline thickness 4 hours after awakening (P < 0.000) and remained stable throughout the day. A small but statistically significant association was found between higher TO and lower CCT (P < 0.0001) and between lower baseline TO and higher PRPH (faster deswelling; P < 0.0001).ConclusionsThe diurnal pattern of TO has been established. The association of TO with corneal thickness and deswelling suggests that the tear film tonicity may be partly responsible for corneal hydration control; however, the effect may not be of clinical significance in a normal study cohort.

PurposeTo investigate the effects of 30 nights of overnight orthokeratology (OOK) on corneal epithelial permeability (Pdc) and corneal biomechanical properties.MethodsBE Retainer and Paragon CRT lenses were used. Visits were scheduled approximately 4 hours after awakening at baseline and after 1, 5, 10, 14, and 30 days of treatment. Pdc was measured at baseline and at day 30, whereas corneal biomechanical properties and visual acuities (VAs) were measured at all visits.ResultsThirty-nine neophytes and soft contact lens wearers completed the study. There was no difference in Pdc between baseline (ln[Pdc] [95% confidence interval (CI)] = -2.65 [-2.80 to -2.50]) and day 30 (ln[Pdc][CI] = -2.68 [-2.85 to -2.50]) (P = 0.88). Corneal hysteresis (CH) and corneal resistance factor (CRF) reduced significantly from baseline (CH [CI] = 10.89 [10.59-11.19] mm Hg and CRF [CI] = 10.35 [9.99-10.72] mm Hg) to day 30 (CH [CI] = 10.59 [10.31-10.87] mm Hg and CRF [CI] = 9.58 [9.26-9.89] mm Hg) (P = 0.001 for CH and P < 0.001 for CRF). Posttreatment VA did not reach baseline targets, and the difference was worse with low-contrast letters. Asian individuals (n = 18) had significantly worse VA than non-Asian individuals (n = 21) under most conditions through day 5, and the difference extended through day 14 with low-contrast letters under mesopic conditions. The percentage of participants who achieved 20/20 uncorrected was 17% Asian and 40% non-Asian individuals after day 1 and reached 69% Asian and 83% non-Asian individuals at day 30.ConclusionsThirty nights of OOK did not alter Pdc when measured 4 hours after awakening. OOK caused CH and CRF to decrease, but the changes were not clinically significant compared with diseased and postsurgical cases. Asian individuals, who had lower baseline CH in this study, responded slower to OOK based on early uncorrected VA and overrefraction measurements.

ObjectivesTo improve the digital quantification of fluorescence intensity of sodium fluorescein instilled on corneal surface by modifying a slit lamp hardware and performing computerized processing of captured digital images.MethodsThe optics of a slit lamp were modified to remove corneal Purkinje reflection and to expand the illuminated area on the cornea, followed by postexperiment image processing to minimize the influence of uneven illumination. To demonstrate the feasibility and reliability of this new technique, we applied it to objective grading of corneal staining with sodium fluorescein. The results of computerized grading were compared with the results obtained using standard subjective grading of corneal staining. Objective digital grades, staining area, and staining pixel with manually and automatically defined threshold (SP-M and SP-A) were calculated for both original and processed images. Standard subjective grades of the original images were performed by 13 trained observers using National Eye Institute (NEI), Efron, and CCLRU grading scales. A series of linear regression analyses were performed to investigate the correlation between objective and subjective grades.ResultsDigital grades of the captured images were correlated significantly with subjective grades. After minimization of the artifact caused by the nonuniform illumination, correlations between digital and subjective grading were mostly strengthened. In some cases, digital grading of corneal staining was more sensitive than subjective grading methods when differentiating subtle differences of corneal staining.ConclusionsModifications performed on commercial slit-lamp hardware and the proposed digital image-processing technique have improved the quality of captured images for semiautomated quantification of fluorescein intensity on the cornea.

PurposeTo determine whether corneal biomechanical properties and intraocular pressure (IOP) are affected by eye rubbing and breath holding.MethodsCorneal hysteresis, corneal resistance factor, corneal compensated IOP (IOPcc), and Goldmann equivalent IOP (IOPg) were measured on both eyes of 40 subjects. Measurements were taken at baseline before eye rubbing (ER(0)) and before breath holding (BH(0)), immediately after 2 episodes of eye rubbing (ER(1) and ER(2)), and during 2 episodes of breath holding (BH(1) and BH(2)).ResultsCorneal hysteresis, corneal resistance factor, and IOPg were significantly lower after ER(1) compared with ER(0) and were significantly lower after ER(2) compared with ER(1). In contrast, IOPcc did not decrease significantly. There were no significant differences among BH(0), BH(1), and BH(2) in any of the 4 outcomes.ConclusionsEye rubbing should be avoided before measurements of corneal biomechanical properties and IOPg. In contrast, breath holding during measurements is not likely to cause a significant change in IOPg and IOPcc or corneal biomechanical properties.

PurposeTo determine whether there are significant differences in standard clinical measures of vision, progressive addition lens (PAL)-specific vision tests, or subjective ratings and preferences between customized free-form and standard non-free-form PALs in an experienced wearing population. In addition, we aim to determine whether subjective or objective clinical outcomes depend on demographic, PAL usage, spectacle prescription, or frame fitting characteristics.MethodsIn a randomized, double-masked cross-over trial, 95 experienced wearers wore Zeiss Individual customized free-form PAL spectacles (test) and standard non-free-form PAL spectacles (control) for 1 week each. At dispensing and after 1 week of wear, subjects were tested for distance and near visual acuity under both high and low contrast; in addition, 30° off-axis visual acuity was measured using a novel apparatus, as was the horizontal extent of clear, undistorted vision at reading distance. Subjects also completed a set of questionnaires detailing their satisfaction levels, adaptation times, and preferences for test or control spectacles for different visual tasks.ResultsThe test spectacles were preferred overall and for distance, midrange, transitional and active vision, and rated higher in overall satisfaction (p = 0.006). There were no clinically important differences between test and control spectacles in standard clinical vision assessments. In the PAL-specific assessments, however, the horizontal extent of clear vision at reading distance was significantly greater with the test spectacles (p = 0.004).ConclusionsThere were statistically significant preferences for the optically customized free-form lenses over the non-free-form lenses. Subjects also reported a wider field of undistorted vision when looking through the reading zone of the test spectacles. Although standard clinical vision assessments are not sufficiently refined to detect important objective differences between the spectacle types, customization taking into account back vertex distance, segment height, pantoscopic tilt, and wrap angle can result in a superior subjective wearing experience for many PAL patients.

PurposeComposed of sheets of cells detached from the underlying conjunctiva, conjunctival epithelial flap (CEF) is a recently reported phenomenon associated with contact lens wear with potential consequences for ocular health. Although CEF is generally asymptomatic, it is not known to what extent it might increase the longer-term risk of discomfort, inflammatory response, or infection. In this study, we use survival analysis methods to obtain unbiased estimates of the probability of developing CEF, the mean survival time free of CEF, and the effects of age, gender, ethnicity, and contact lens type.MethodsTwo hundred four subjects were recruited for a continuous wear (CW) study of silicone hydrogel (SiH) and gas permeable (GP) contact lenses. Subjects were examined by optometrists throughout contact lens adaptation and CW periods. Statistical methods included the Kaplan-Meier nonparametric estimator of the survival function and the Cox proportional hazards model for estimating the relative effects of covariates.ResultsOf the 204 subjects, 72 (35%) developed CEF. In 64% of cases, CEFs were observed bilaterally. The majority of cases (90.3%) presented with CEF in the superior conjunctiva. Mean survival time free of CEF was longer for GP lenses (94.3 days) than for SiH lenses (76.5 days), and the probability of developing CEF was significantly greater for SiH lenses (p = 0.002). Although there was some evidence that women and non-Asians remain free of CEF longer, the effects of age, gender, and ethnicity were not statistically significant.ConclusionsThere was a significantly increased risk of CEF in subjects wearing SiH lenses, compared with GP lenses. Subjects wearing SiH lenses remained free of CEF for a shorter time on average. Further study is needed to determine whether the increased incidence of CEF in CW with SiH lenses poses an increased risk of adverse ocular response or infection.

PURPOSE:To assess the effects of soft contact lens base curve radius (BCR), sex, ethnicity, central corneal curvatures, and vertical palpebral aperture size (PAS) on the postlens tear thickness (PLTT). METHODS:The PLTT was measured using optical pachometry on 114 experienced lens wearers who were fitted with lathe-cut soft lenses (Alden 47, polymacon, 35.5% H2O, -2.00 diopter, and 14.0 mm). Each subject was randomly allocated to one lens group receiving a BCR of 7.9, 8.3, or 8.7 mm. Pachometry measurements were taken at 30 min after lens insertion. Vertical PAS and keratometry readings were measured for 94 of the 114 subjects. RESULTS:The mean (95% confidence interval) PLTT was 15.7 microm (13.2-18.0 microm), 12.8 microm (10.9-14.7 microm), and 12.1 microm (10.2-14.0 microm) for the 7.9-mm, 8.3-mm, and 8.7-mm BCR groups, respectively. The differences in PLTT among the three BCR groups was significant (analysis of variance F-test; P=0.039). Post hoc testing using the Tukey honestly significant difference statistic showed that only the two extreme BCR groups (7.9 mm and 8.7 mm) were significantly different. Sex had no effect on the PLTT; however, the PLTT was significantly thinner for the Asian compared with non-Asian eyes (P=0.0001). The Asian PLTT did not vary with different soft lens BCRs. The non-Asian PLTT was thicker with lenses of the steep BCR compared with the flat BCR. CONCLUSION:These results show that the base curve radius of a soft contact lens and several ocular characteristics can affect the thickness of the postlens tear film.

PurposeTo measure the effect of hypoxia and eye closure on epithelial permeability to fluorescein (P(dc)) during rigid lens extended wear (EW).MethodsCentral corneal thickness (CT) and P(dc) were measured in 42 subjects with an optical pachometer and automated scanning fluorophotometer, respectively. All subjects had been successfully wearing rigid gas-permeable (RGP) lenses on a 6-night EW regimen, and each individual was randomized to wear either medium- or high-oxygen-permeable (Dk) RGP lenses (two types of siloxane-fluorocarbon polymer lenses with Dk of 49 and 92). CT and P(dc) measurements were performed at an afternoon visit (baseline) and were repeated in the morning after 8 hours of overnight wear. Subjects slept with a patch over the right eye. The patch was not removed until immediately before the morning measurement.ResultsThe mean overnight swelling response for subjects in the medium-Dk group was greater than that in the high-Dk group. Results of a paired t-test indicate that the eye wearing the medium-Dk lens with a patch overnight had a significant increase in epithelial permeability. Results of mixed-effect models suggest that eye closure and lens-induced hypoxia are significant factors in altering P(dc).ConclusionsThe results indicate that corneal epithelial permeability increases with hypoxic dose and that epithelial barrier function is impaired by overnight rigid lens wear.

ObjectiveTo describe the principal clinical outcomes associated with 12 months use of rigid gas-permeable (RGP) extended wear contact lenses and address two primary study questions: (1) does extended wear (EW) of high oxygen transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications, and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to maintain 6-night RGPEW over 12 months?DesignA randomized, concurrently controlled clinical trial.InterventionSubjects who adapted to EW with high Dk (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk RGP lenses for 12 months of 6-night EW.Main outcome measuresContact lens-associated keratopathies (CLAK), changes in refractive error and corneal curvature, and survival in EW.ResultsTwo hundred one subjects were randomized to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the subjects in each group completed 12 months of EW; however, the probability of failure was significantly greater for the medium-Dk group. Although the risk of complications was similar for the two groups, the number of CLAK events that led to termination were 16 versus 5 for the medium-Dk and high-Dk groups, respectively. This suggests that the type of adverse response or the inability to reverse an adverse event was different for the group being exposed to the lower oxygen dose.ConclusionsThe level of oxygen available to the cornea has a significant impact on maintaining successful RGP extended contact lens wear, but not on the initial onset of CLAK. The number of clinical events leading to termination was substantially higher for the medium Dk group, which suggests that corneal hypoxia is an important factor in the development of CLAK. Although overnight contact lens wear should be recommended with caution and carefully monitored for early detection of ocular complications, it appears that high-Dk RGP lenses can be a safe and effective treatment for correction of refractive error for most individuals who can adapt to EW.

ObjectiveThe primary aim of the Berkeley Contact Lens Extended Wear Study (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence of contact lens-associated keratopathy (CLAK) and increases the survival rate in RGP extended wear (EW). In this article we describe the clinical trial design in detail, present the results of subject recruitment and retention, and provide the baseline demographic and ocular characteristics of the CLEWS subjects, whose data will be analyzed to address the study aims in a companion article.DesignA randomized, concurrently controlled clinical trial.InterventionSubjects were fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses for 12 months of 6-nights/week EW.Main outcome measuresSlit-lamp assessment and grading of 17 possible keratopathies, measurement of refractive error and corneal curvature, and symptoms. Follow-up data were collected every 3 months.ResultsFrom 545 subjects entering the DW adaptation phase, 201 adapted to EW and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The baseline characteristics of the two study groups were similar and did not differ from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen transmissibility for the two study groups were disjoint, indicating that each group received distinctly different levels of hypoxia.ConclusionsWe show that CLEWS was appropriately designed to address the study hypotheses, was conducted with regard for the safety of the subjects, and adhered to rigorous protocols designed to control for bias and ensure the integrity of study data. We establish the internal validity of between-group statistical comparisons and characterize our study population to permit informed evaluation of the applicability of our results to the contact lens-wearing population in general.