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Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in ageing-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate ageing remains unclear. Here we report a fat-to-neuron lipid signalling pathway induced by lysosomal metabolism and its longevity-promoting role in Caenorhabditis elegans. We discovered that induced lysosomal lipolysis in peripheral fat storage tissue upregulates the neuropeptide signalling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a specific polyunsaturated fatty acid, dihomo-γ-linolenic acid, and LBP-3 lipid chaperone protein transported from the fat storage tissue to neurons. LBP-3 binds to dihomo-γ-linolenic acid, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signalling hub to coordinate metabolism and ageing, and lysosomal signalling mediated inter-tissue communication in promoting longevity.

SignificanceQuantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images.PurposeMeibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features.MethodsA total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity.ResultsA total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands.ConclusionsThe proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quantitatively analyze gland morphological features.

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.

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.

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.

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.

SIGNIFICANCE:A corneal heat-transfer model is presented to quantify simultaneous measurements of fluorescein tear-breakup area (TBA) and ocular-surface temperature (OST). By accounting for disruption of the tear-film lipid layer (TFLL), we report evaporation rates through lipid-covered tear. The modified heat-transfer model provides new insights into evaporative dry eye. PURPOSE:A quantitative analysis is presented to assess human aqueous tear evaporation rate (TER) through intact TFLLs from simultaneous in vivo measurement of time-dependent infrared OST and fluorescein TBA. METHODS:We interpret simultaneous OST and TBA measurements using an extended heat-transfer model. We hypothesize that TBAs are ineffectively insulated by the TFLL and therefore exhibit higher TER than does that for a well-insulting TFLL-covered tear. As time proceeds, TBAs increase in number and size, thereby increasing the cornea area-averaged TER and decreasing OST. Tear-breakup areas were assessed from image analysis of fluorescein tear-film-breakup video recordings and are included in the heat-transfer description of OST. RESULTS:Model-predicted OSTs agree well with clinical experiments. Percent reductions in TER of lipid-covered tear range from 50 to 95% of that for pure water, in good agreement with literature. The physical picture of noninsulating or ruptured TFLL spots followed by enhanced evaporation from underlying cooler tear-film ruptures is consistent with the evaporative-driven mechanism for local tear rupture. CONCLUSIONS:A quantitative analysis is presented of in vivo TER from simultaneous clinical measurement of transient OST and TBA. The new heat-transfer model accounts for increased TER through expanding TBAs. Tear evaporation rate varies strongly across the cornea because lipid is effectively missing over tear-rupture troughs. The result is local faster evaporation compared with nonruptured, thick lipid-covered tear. Evaporative-driven tear-film ruptures deepen to a thickness where fluorescein quenching commences and local salinity rises to uncomfortable levels. Mitigation of tear-film rupture may therefore reduce dry eye-related symptoms.

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.

SIGNIFICANCE A simple methodology is presented to quantify basal tear production with a modified Schirmer-tear test.PURPOSE We introduce a simple clinical procedure to measure quantitative basal tear-production flowrates, QL, from a modified Schirmer-tear test (STT).METHODS Eight 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.RESULTS Basal tear production rates varied from essentially 0 to about 2 μl/min. With some exceptions, right and left eyes showed similar tear production rates.CONCLUSIONS By 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.

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.

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.

The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms.

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.

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.

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 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.

PurposeTo determine the effects on corneal epithelial permeability and ocular response of 30 nights of continuous wear (CW) of gas permeable (GP) and silicone hydrogel (SiH) contact lenses.MethodsNinety-one subjects successfully completed 30 days of CW of either GP (n = 42) or SiH (n = 49) contact lenses. Epithelial permeability (P(dc)) was measured by scanning fluorometer at an afternoon (PM) baseline session and again the next morning (AM). One randomly selected eye of each subject was patched overnight and the patch removed immediately before the AM visit. P(dc) measurements and ocular examinations were conducted at baseline and after 30 days of CW.ResultsEpithelial permeability increased significantly after 30 days of CW in the patched eyes of the GP group (P = 0.022) and in the unpatched eyes of the SiH group (P = 0.004). The increase was driven primarily by the Asian subjects in each group (GP, P = 0.015; SiH, P = 0.001). There was no significant increase in either lens group in the non-Asian subjects. Multivariate models suggest that the change in AM P(dc) from baseline to 30 days of CW was also related to lens type (P = 0.035), time awake before measurement (P = 0.001), palpebral aperture size (P = 0.003), lens deposits (P = 0.020), and horizontal lens bearing (P = 0.003).ConclusionsSubclinical increases in epithelial permeability can be caused by contact lens CW, despite the elimination of hypoxia. GP lenses permit recovery of the epithelium more quickly than do SiH lenses. Asians appear to be more susceptible to contact lens-induced epithelial changes than do non-Asians.

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.

PurposeTo investigate the release of surface-active agents (surfactants) from unworn soft contact lenses (SCLs) and their influence on the lens surface wettability in vitro.MethodsSurface tension (ST) of blister pack solutions was measured by pendant-drop technique. STs at the air-aqueous interface and contact angles (CAs) of four conventional and seven silicone hydrogel SCLs were evaluated in a dynamic-cycling regime using a modified captive-bubble tensiometer-goniometer. Measurements were performed immediately after removal from blister packs, and after soaking in a glass vial filled with a surfactant-free solution, which was replaced daily for 1 week. Lens surface wettability was expressed as adhesion energy according to Young equation.ResultsSTs of all blister pack solutions were lower than the reference ST of pure water (72.5 mN/m), indicating the presence of surfactants. When lenses were depleted of surfactants by soaking, the STs for all studied lenses and advancing CAs of selected lenses increased (p < 0.001). Receding CAs of all studied lenses were 12 degrees +/- 5 degrees and were not affected by the presence of surfactants. For most of the conventional lenses, the surface wettability was largely dependent on surfactants, and reduced significantly after surfactant depletion. In contrast, most silicone hydrogel lenses exhibited stable and self-sustained surface wettability in vitro.ConclusionsThe manufacturer-added surfactants affected wetting properties of all studied SCLs, although to different degrees.

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.

PurposeTear exchange under a soft contact lens is directly related to the amount of lateral and transverse lens motion. Hydrodynamic modeling suggests that channels placed on the back surface of a soft lens will reduce fluid resistance and increase transverse lens movement. This study measured the effect of posterior lens surface scalloped channels on tear exchange.MethodsTear exchange in the postlens tear film (PoLTF) was estimated using a fluorometer to measure the exponential depletion of high-MW fluorescein under the lens expressed as the time to deplete 95% of dye (T95). A total of 32 subjects wore two pairs of identical lenses except that the experimental lens had 12 scalloped channels placed radially in the midperiphery of the posterior lens surface, whereas lenses without channels served as controls.ResultsThe mean +/- standard error T95 values for the channel lenses was 28 +/- 2 minutes compared with 32 +/- 2 minutes for the control lenses (p = 0.107). There was a marginally significant difference in T95 between two lens groups in Asian eyes (p = 0.054).ConclusionPlacing scallop-shaped channels on high-H2O content soft lenses improved the postlens tear pumping in Asian eyes.

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.