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.

Tear-film evaporation flux and its relationship to tear properties in symptomatic and asymptomatic soft-contact-lens wearers.

PURPOSE: With soft-contact-lens wear, evaporation of the pre-lens tear film affects the osmolarity of the post-lens tear film and this can introduce a hyperosmotic environment at the corneal epithelium, leading to discomfort. The purposes of the study are to ascertain whether there are differences in evaporation flux (i.e., the evaporation rate per unit area) between symptomatic and asymptomatic soft-contact-lens wearers, to assess the repeatability of a flow evaporimeter, and to assess the relationship between evaporation fluxes, tear properties, and environmental conditions. METHODS: Closed-chamber evaporimeters commonly used in ocular-surface research do not control relative humidity and airflow, and, therefore, misestimate the actual tear-evaporation flux. A recently developed flow evaporimeter overcomes these limitations and was used to measure accurate in-vivo tear-evaporation fluxes with and without soft-contact-lens wear for symptomatic and asymptomatic habitual contact-lens wearers. Concomitantly, lipid-layer thickness, ocular-surface-temperature decline rate (i.e., °C/s), non-invasive tear break-up time, tear-meniscus height, Schirmer tear test, and environmental conditions were measured in a 5 visit study. RESULTS: Twenty-one symptomatic and 21 asymptomatic soft-contact-lens wearers completed the study. A thicker lipid layer was associated with slower evaporation flux (p < 0.001); higher evaporation flux was associated with faster tear breakup irrespective of lens wear (p = 0.006). Higher evaporation flux was also associated with faster ocular-surface-temperature decline rate (p < 0.001). Symptomatic lens wearers exhibited higher evaporation flux than did asymptomatic lens wearers, however, the results did not reach statistical significance (p = 0.053). Evaporation flux with lens wear was higher than without lens wear but was also not statistically significant (p = 0.110). CONCLUSIONS: The repeatability of the Berkeley flow evaporimeter, associations between tear characteristics and evaporation flux, sample-size estimates, and near statistical significance in tear-evaporation flux between symptomatic and asymptomatic lens wearers all suggest that with sufficient sample sizes, the flow evaporimeter is a viable research tool to understand soft-contact-lens wear comfort.

Predicting demographics from meibography using deep learning.

This study introduces a deep learning approach to predicting demographic features from meibography images. A total of 689 meibography images with corresponding subject demographic data were used to develop a deep learning model for predicting gland morphology and demographics from images. The model achieved on average 77%, 76%, and 86% accuracies for predicting Meibomian gland morphological features, subject age, and ethnicity, respectively. The model was further analyzed to identify the most highly weighted gland morphological features used by the algorithm to predict demographic characteristics. The two most important gland morphological features for predicting age were the percent area of gland atrophy and the percentage of ghost glands. The two most important morphological features for predicting ethnicity were gland density and the percentage of ghost glands. The approach offers an alternative to traditional associative modeling to identify relationships between Meibomian gland morphological features and subject demographic characteristics. This deep learning methodology can currently predict demographic features from de-identified meibography images with better than 75% accuracy, a number which is highly likely to improve in future models using larger training datasets, which has significant implications for patient privacy in biomedical imaging.

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.

Prevention of localized corneal hyperosmolarity spikes by soft-contact-lens wear.

PURPOSE: To determine whether localized hyperosmotic spikes on the pre-lens tear film (PrLTF) due to tear break up results in hyperosmotic spikes on the ocular surface during soft-contact-lens (SCL) wear and whether wear of SCLs can protect the cornea against PrLTF osmotic spikes. METHODS: Two-dimensional transient diffusion of salt was incorporated into a computationally designed SCL, post-lens tear film (PoLTF), and ocular surface and solved numerically. Time-dependent localized hyperosmolarity spikes were introduced at the anterior surface of the SCL corresponding to those generated in the PrLTF. Salt spikes were followed in time until spikes penetrate through the lens into the PoLTF. Lens-salt diffusivities (Ds) were varied to assess their importance on salt migration from the PrLTF to the ocular surface. SCL and PoLTF initial conditions and the lens anterior-surface boundary condition were varied depending on the value of Ds and on dry-eye symptomatology. Determined corneal surface osmolarities were translated into clinical pain scores. RESULTS: For Ds above about 10-7cm2/s, it takes around 5-10 s for the PrLTF hyperosmotic break-up spikes to diffuse across the SCL and reach the corneal surface. Even if localized hyperosmotic spikes penetrate to the ocular surface, salt concentrations there are much lower than those in the progenitor PrLTF spikes. For Ds less than 10-7cm2/s, the SCL protects the cornea from hyperosmotic spikes for both normal and dry eyes. When localized corneal hyperosmolarity is converted into transient pain scores, pain thresholds are significantly lower than those for no-lens wear. CONCLUSIONS: A cornea can be protected from localized PrLTF hyperosmolarity spikes with SCL wear. With regular blinking (e.g., less than 10 s), SCL wear shields the cornea from significant hyperosmotic pain. Decreasing Ds increases that protection. Low-Ds soft contact lenses can protect against hyperosmotic spikes and discomfort even during infrequent blinking (e.g., > 10 s).

Central-to-peripheral corneal edema during wear of embedded-component contact lenses.

PURPOSE: With active investigation underway for embedded-circuit contact lenses, safe oxygen supply of these novel lenses remains a question. Central-to-peripheral corneal edema for healthy eyes during wear of soft contact (SCL) and scleral lenses (SL) with embedding components is assessed. METHODS: Various 2-dimensional (2D) designs of SL and SCL with embedded components are constructed on Comsol Multiphysics 5.5. Local corneal swelling associated with the designed lenses is determined by a recently developed 2D metabolic-swelling model. Settled central post-lens tear-film thicknesses (PoLTFs) are set at 400 µm and 3 µm for SL and SCL designs, respectively. Each lens design has an axisymmetric central and an axisymmetric peripheral embedment. Oxygen permeability (Dk) of the lens and the embedments ranges from 0 to 200 Barrer. Dimensions and location of the embedments are varied to assess optimal-design configurations to minimize central-to-peripheral corneal edema. RESULTS: By adjusting oxygen Dk of the central embedment, the peripheral embedment, or the lens matrix polymer, corneal swelling is reduced by up to 2.5 %, 1.5 %, or 1.4 % of the baseline corneal thickness, respectively, while keeping all other parameters constant. A decrease in PoLTF thickness from 400 µm to 3 µm decreases corneal edema by up to 1.8 % of the baseline corneal thickness. Shifting the peripheral embedment farther out towards the periphery and towards the anterior lens surface reduces peak edema by up to 1.3 % and 0.6 % of the baseline corneal thickness, respectively. CONCLUSIONS: To minimize central-to-peripheral corneal edema, embedments should be placed anteriorly and far into the periphery to allow maximal limbal metabolic support and oxygen transport in the polar direction (i.e., the θ-direction in spherical coordinates). High-oxygen transmissibility for all components and thinner PoLTF thickness are recommended to minimize corneal edema. Depending on design specifications, less than 1 % swelling over the entire cornea is achievable even with oxygen-impermeable embedments.

Protection against corneal hyperosmolarity with soft-contact-lens wear.

Hyperosmotic tear stimulates human corneal nerve endings, activates ocular immune response, and elicits dry-eye symptoms. A soft contact lens (SCL) covers the cornea preventing it from experiencing direct tear evaporation and the resulting blink-periodic salinity increases. For the cornea to experience hyperosmolarity due to tear evaporation, salt must transport across the SCL to the post-lens tear film (PoLTF) bathing the cornea. Consequently, limited salt transport across a SCL potentially protects the ocular surface from hyperosmotic tear. In addition, despite lens-wear discomfort sharing common sensations to dry eye, no correlation is available between measured tear hyperosmolarity and SCL-wear discomfort. Lack of documentation is likely because clinical measurements of tear osmolarity during lens wear do not interrogate the tear osmolarity of the PoLTF that actually overlays the cornea. Rather, tear osmolarity is clinically measured in the tear meniscus. For the first time, we mathematically quantify tear osmolarity in the PoLTF and show that it differs significantly from the clinically measured tear-meniscus osmolarity. We show further that aqueous-deficient dry eye and evaporative dry eye both exacerbate the hyperosmolarity of the PoLTF. Nevertheless, depending on lens salt-transport properties (i.e., diffusivity, partition coefficient, and thickness), a SCL can indeed protect against corneal hyperosmolarity by reducing PoLTF salinity to below that of the ocular surface during no-lens wear. Importantly, PoLTF osmolarity for dry-eye patients can be reduced to that of normal eyes with no-lens wear provided that the lens exhibits a low lens-salt diffusivity. Infrequent blinking increases PoLTF osmolarity consistent with lens-wear discomfort. Judicious design of SCL material salt-transport properties can ameliorate corneal hyperosmolarity. Our results confirm the importance of PoLTF osmolarity during SCL wear and indicate a possible relation between PoLTF osmolarity and contact-lens discomfort.

Correlation of Measures From the OCULUS Keratograph and Clinical Assessments of Dry Eye Disease in the Dry Eye Assessment and Management Study.

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

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.

Ocular surface cooling rate associated with tear film characteristics and the maximum interblink period.

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

The relationship of pre-corneal to pre-contact lens non-invasive tear breakup time.

PURPOSE: To examine the relationship between pre-corneal and pre-contact lens tear film stability (TFS), and to determine whether pre-corneal TFS is a reliable predictor of subsequent pre-lens TFS after a contact lens is placed on the eye. METHODS: 667 records met inclusion criteria and were extracted from a soft contact lens multi-study database. Multivariable linear mixed effects models were fit to examine the association between pre-corneal and pre-lens TFS, adjusting for potential confounders and accounting for repeated measures. Receiver Operating Characteristic (ROC) analysis was employed to assess the predictive performance of pre-corneal TFS for subsequent pre-lens TFS. TFS was quantified for this analysis as the non-invasive tear breakup time (NITBUT). RESULTS: Pre-corneal NITBUT was significantly related to the pre-lens NITBUT at both 10 min (p<0.001) and 2-6 hrs (p<0.001) post-lens insertion. However, the sensitivities of pre-corneal NITBUT for predicting symptom-associated thresholds of pre-lens NITBUT ranged from 50-65%, and specificities ranged from 57-72%, suggesting poor-to-moderate diagnostic performance. CONCLUSIONS: Despite the association of pre-corneal and pre-lens TFS, the inherent lability and sensitivity to environmental exposures of the tear film introduce significant variability into NITBUT measurements. Using pre-corneal NITBUT to identify likely successful contact lens candidates prior to fitting is thus not sufficiently accurate to be relied upon in the clinical setting.

Meibography Phenotyping and Classification From Unsupervised Discriminative Feature Learning.

Purpose: The purpose of this study was to develop an unsupervised feature learning approach that automatically measures Meibomian gland (MG) atrophy severity from meibography images and discovers subtle relationships between meibography images according to visual similarity. Methods: One of the latest unsupervised learning approaches is to apply feature learning based on nonparametric instance discrimination (NPID), a convolutional neural network (CNN) backbone model trained to encode meibography images into 128-dimensional feature vectors. The network aims to learn a similarity metric across all instances (e.g. meibography images) and groups visually similar instances together. A total of 706 meibography images with corresponding meiboscores were collected and annotated for the use of network learning and performance evaluation. Results: Four hundred ninety-seven meibography images were used for network learning and tuning, whereas the remaining 209 images were used for network model evaluations. The proposed nonparametric instance discrimination approach achieved 80.9% meiboscore grading accuracy on average, outperforming the clinical team by 25.9%. Additionally, a 3D feature visualization and agglomerative hierarchical clustering algorithms were used to discover the relationship between meibography images. Conclusions: The proposed NPID approach automatically analyses MG atrophy severity from meibography images without prior image annotations, and categorizes the gland characteristics through hierarchical clustering. This method provides quantitative information on the MG atrophy severity based on the analysis of phenotypes. Translational Relevance: The study presents a Meibomian gland atrophy evaluation method for meibography images based on unsupervised learning. This method may be used to aid diagnosis and management of Meibomian gland dysfunction without prior image annotations, which require time and resources.

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.

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.

Evaporation retardation by model tear-lipid films: The roles of film aging, compositions and interfacial rheological properties.

A novel methodology for assessing evaporation (up to 48 h) through lipid-nanofilms in vitro was developed. The influence of lipid-mixture compositions on evaporation rates was studied. The evaporative fluxes and rheology of lipid-nanofilms were compared with those of human tear-lipid nanofilms in vitro.A sessile-drop technique with precise drop-volume control was adapted to measure evaporation rates at constant temperature of 36 °C and humidity of 75 %. Model lipid solutions were deposited on the surface of aqueous drops to create nanofilms of 10-100 nm. The measurements of dynamic surface pressure vs. nanofilm-thickness were performed under the same conditions. The lipid-mixtures compositions were chosen to mimic that of human tear lipids. Evaporation through lipid nanofilms decreased with film thickness and aging. Evaporation through 70-nm films was 2.5-3 time slower than through 10-nm-thick films. Nonpolar-lipid mixtures reduced evaporation by approximately 35 %. The optimized model-lipid mixtures containing polar phospholipids reduced evaporation by 70-75 %, matching the evaporation-reduction by human-lipid nanofilms in vitro. These model mixtures exhibited interfacial rheology similar to human tear lipids in vitro.This methodology substantiated that aged lipid-nanofilms significantly reduced evaporation in vitro. These findings contradict to the previous reports suggesting that model lipid and meibum films do not retard evaporation in vitro. Polar phospholipids enhance evaporative resistance close to the level observed for human tear-lipid films in vivo. We hypothesize that unique rheological properties of tear-lipid nanofilms are germane to the specific mono- and bi-layered structures formed by phospholipids at the lipid-air and lipid-aqueous interfaces.

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.

Limbal Metabolic Support Reduces Peripheral Corneal Edema with Contact-Lens Wear.

Purpose: To assess the influence of limbal metabolic support on corneal edema during scleral-lens (SL) and soft-contact-lens (SCL) wear for healthy lens wearers. Methods: A two-dimensional (2D) model of the cornea and sclera was designed on Comsol Multiphysics 5.4 along with SL and SCL architectures to mimic lens-wear induced hypoxia. The cornea is suffused with oxygen and metabolites from the limbus and aqueous humor. Air oxygen is supplied from and carbon dioxide is expelled to the atmosphere. Lens-oxygen permeability (Dk) was adjusted to investigate lens-wear safety against edema in different wear conditions. The 2D concentrations of oxygen, carbon dioxide, bicarbonate, lactate, sodium, chloride, glucose, and pH are quantified. Central-to-peripheral swelling of the cornea is determined by the change in stromal hydration caused by changing metabolite concentrations at the endothelium during hypoxia. Results: The metabolic model assesses central-to-peripheral corneal swelling with different types of lenses, and oxygen Dks. Limbal metabolic support reduces edema from the periphery to approximately 1 mm away from the central cornea. Despite thicker lens designs, the peripheral cornea exhibits practically zero swelling due to limbal metabolic support. Conclusions: The metabolic model accurately predicts central-to-peripheral corneal edema with various contact-lens designs, post-lens tear-film thicknesses, and lens oxygen Dk values. Despite the thicker periphery of most contact-lens designs, lactate and bicarbonate support from the limbus significantly reduces peripheral and mid-peripheral corneal edema, whereas oxygen has a lesser effect. Translational Relevance: By utilizing metabolic kinetics, we provide a 2D computational tool to predict oxygenation safety across the entire cornea with various types and designs of contact lenses.

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making.

Diffuse lamellar keratitis associated with tabletop autoclave biofilms: case series and review.

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