Effect of Scleral Contact Lens Size and Duration of Wear on Intraocular Pressure.

OBJECTIVE: To evaluate the effects of scleral lens size and the duration of wear on intraocular pressure (IOP) during lens wear. METHODS: Healthy adults were recruited for this prospective and randomized study. Intraocular pressure measurements were performed using a pneumotonometer. A block randomization was used to assign the order of scleral lens diameter of either 15.6 mm or 18.0 mm for 5-hr bilateral wear over a course of two visits. Scleral IOP (sIOP) was measured during the predetermined intervals, 1.25 hr apart, during the 5-hr scleral lens wear. Corneal IOP (cIOP) was measured before and after the scleral lens wear. The primary outcome measure was the mean change in sIOP from prelens insertion baseline. RESULTS: Corneal IOP unchanged after scleral lens removal compared with the baseline measurements ( P =0.878). Smaller and larger lenses introduced significantly higher sIOP at 2.5 hr after lens insertion with the mean (95% CI) increase of 1.16 (0.54, 1.78) mm Hg and 1.37 (0.76, 1.99) mm Hg, respectively. There was no difference in IOP change between the smaller and larger diameter lenses ( P =0.590). CONCLUSIONS: Well-fitted scleral lenses do not result in clinically significant changes in intraocular pressure during 5-hr lens wear in young and healthy individuals.

Clinical Report: Midday Removal and Reinsertion of Soft Contact Lens Cannot Prevent Post-lens Tear-film Hyperosmolarity.

SIGNIFICANCE: Our analysis shows that post-lens tear-film (PoLTF) hyperosmolarity is not preventable with midday removal and reinsertion of soft contact lenses. However, low lens-salt diffusivity can prevent the PoLTF from becoming hyperosmotic. Lens-salt diffusivity should be lowered to minimize PoLTF osmolarity while also avoiding lens adhesion. PURPOSE: Soft contact lenses with high lens-salt diffusivity result in hyperosmotic PoLTFs. If the time it takes for PoLTF osmolarity to reach periodic steady state is multiple hours, simple midday lens removal and reinsertion can prevent the PoLTF from becoming hyperosmotic. We investigate whether midday removal and reinsertion of a soft contact lens can prevent the PoLTF from becoming hyperosmotic. METHODS: Time to periodic steady state for PoLTF osmolarity upon soft-contact-lens wear is determined with a previously developed transient tear-dynamics continuum model. Interblink period, lens-salt diffusivity, and lens thickness was varied to assess their effects on time to periodic steady state for PoLTF osmolarity. Time to periodic steady states were assessed for both normal and dry eyes. RESULTS: Within the physically realistic ranges of lens-salt diffusivity, lens thickness, and interblink period, PoLTF osmolarity reaches the periodic steady state well within the first hour of lens wear for both normal and dry eyes. Time to periodic steady state for PoLTF osmolarity is predominately dictated by the salt transport across the contact lens between the PoLTF and the pre-lens tear film and water transport from the ocular surface to the PoLTF. CONCLUSIONS: Since the time to periodic steady state is less than 1 hour for physically realistic ranges of lens-salt diffusivity, interblink period, and lens thickness, midday lens removal and reinsertion cannot prevent PoLTF hyperosmolarity. Instead, focus should be on using soft contact lenses with low salt diffusivity to prevent PoLTF hyperosmolarity.

n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease.

BACKGROUND: Dry 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. METHODS: In 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. RESULTS: A 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. CONCLUSIONS: Among 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 .).

Meibomian Gland Contrast Sensitivity and Specificity in the Diagnosis of Lipid-deficient Dry Eye: A Pilot Study.

SIGNIFICANCE: Lipid 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. PURPOSE: This study aimed to determine the sensitivity and specificity of MG contrast for the diagnosis of lipid-deficient dry eye (LDDE). METHODS: This 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). RESULTS: Thirty-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). CONCLUSIONS: Meibomian 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.

Quantifying Meibomian Gland Morphology Using Artificial Intelligence.

SIGNIFICANCE: Quantifying 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. PURPOSE: Meibomian 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: The proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quantitatively analyze gland morphological features.

Associations Between Systemic Omega-3 Fatty Acid Levels With Moderate-to-Severe Dry Eye Disease Signs and Symptoms at Baseline in the Dry Eye Assessment and Management Study.

PURPOSE: Omega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study. METHODS: Blood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer's test with anesthesia were also evaluated. RESULTS: There was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3. CONCLUSION: Previous studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.

Corneal Health during Three Months of Scleral Lens Wear.

SIGNIFICANCE: This 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. PURPOSE: This 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. METHODS: Twenty-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. RESULTS: The 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). CONCLUSIONS: Scleral 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.

Not All Dry Eye in Contact Lens Wear Is Contact Lens-Induced.

OBJECTIVES: To 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. METHODS: Ninety-two subjects completed the Berkeley Dry Eye Flow Chart with and without lenses, ocular surface examinations, and a battery of questionnaires. RESULTS: Thirty-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<0.001) but did not distinguish CLIDE from DE. The DE group was significantly worse than CLIDE and ASYM, which were similar, in precorneal noninvasive tear breakup time (8.2 sec DE vs. 12.3 sec CLIDE and 14.3 sec ASYM; P=0.002), anterior displacement of the Line of Marx (P=0.017), and superior conjunctival staining (P=0.001). CONCLUSIONS: Many CL wearers presenting with dryness symptoms have an underlying DE condition and will not respond to treatments aimed at changing lenses or solutions. Contradictory results from research studies of DE in CL wearers could be due in part to a failure to distinguish subjects with symptoms due specifically to CL wear from those whose symptoms have underlying causes unrelated to CL wear.

Impact of Dry Eye on Visual Acuity and Contrast Sensitivity: Dry Eye Assessment and Management Study.

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.

Tear-Film Evaporation Rate from Simultaneous Ocular-Surface Temperature and Tear-Breakup Area.

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.

Effects of Scleral-lens Tear Clearance on Corneal Edema and Post-lens Tear Dynamics: A Pilot Study.

SIGNIFICANCE: The 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. PURPOSE: The 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. METHODS: Neophytes 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. RESULTS: The 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). CONCLUSIONS: Within 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.

Human Lacrimal Production Rates from Modified Schirmer-Tear Test.

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.

Effects of Lens-Care Solutions on Hydrogel Lens Performance.

SIGNIFICANCE: Lens care multipurpose solutions (MPSs) can have varying effects on contact lens (CL) surface properties and the corneal epithelium. PURPOSE: The 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. METHODS: Acuvue 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. RESULTS: At 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. CONCLUSIONS: Differences 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.

Accounting for Ethnicity-Related Differences in Ocular Surface Integrity as a Step Toward Understanding Contact Lens Discomfort.

Contact lens discomfort is a common problem that can lead to unsuccessful or limited contact lens wear. Although many factors may contribute to contact lens discomfort, limited research has explored the influence of ethnicity-related differences in the anatomy and physiology of the ocular surface. Therefore, we performed a search of the literature in PubMed using key words related to "ocular surface" paired with the terms "race" and "ethnicity." The goal of this review was to determine potential areas of research regarding ethnicity differences, particularly between Asian and non-Asian eyes, in ocular surface integrity to advance our understanding of contact lens discomfort.

Directional Optical Coherence Tomography Reveals Reliable Outer Nuclear Layer Measurements.

PURPOSE: Directional 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. METHODS: Sixteen 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. RESULTS: All 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. CONCLUSIONS: ONL 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.

Improving Care for Patients with Dry Eye Symptoms: See What the Experts Say.

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?

Ocular Surface Cooling Corresponds to Tear Film Thinning and Breakup.

PURPOSE: To investigate the relationship between ocular surface temperature (OST) and tear film thinning and breakup. METHODS: Simultaneous 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. RESULTS: Areas 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. CONCLUSIONS: The 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.

Clinical Outcomes Associated with Thermal Pulsation System Treatment.

PURPOSE: To 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. METHODS: Thirty-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). RESULTS: Baseline 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. CONCLUSIONS: Our results identified factors that better select candidates for LipiFlow Thermal Pulsation System.

Effects of Isotretinoin on Meibomian Glands.

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.