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PURPOSE: This study enhances Meibomian gland (MG) infrared image analysis in dry eye (DE) research through artificial intelligence (AI). It is comprised of two main stages: automated eyelid detection and tarsal plate segmentation to standardize meibography image analysis. The goal is to address limitations of existing assessment methods, bridge the curated and real-world dataset gap, and standardize MG image analysis. METHODS: The approach involves a two-stage process: automated eyelid detection and tarsal plate segmentation. In the first stage, an AI model trained on curated data identifies relevant eyelid areas in non-curated datasets. The second stage refines the eyelid area in meibography images, enabling precise comparisons between normal and DE subjects. This approach also includes specular reflection removal and tarsal plate mask refinement. RESULTS: The methodology achieved a promising instance-wise accuracy of 80.8% for distinguishing meibography images from 399 DE and 235 non-DE subjects. By integrating diverse datasets and refining the area of interest, this approach enhances meibography feature extraction accuracy. Dimension reduction through Uniform Manifold Approximation and Projection (UMAP) allows feature visualization, revealing distinct clusters for DE and non-DE phenotypes. CONCLUSIONS: The AI-driven methodology presented here quantifies and classifies meibography image features and standardizes the analysis process. By bootstrapping the model from curated datasets, this methodology addresses real-world dataset challenges to enhance the accuracy of meibography image feature extraction. TRANSLATIONAL RELEVANCE: The study presents a standardized method for meibography image analysis. This method could serve as a valuable tool in facilitating more targeted investigations into MG characteristics.

This study sought to assess the association between axial length (AL) and diabetic retinopathy (DR) in a diverse cohort of patients and to investigate the impact of sex on this relationship. An urban safety net hospital database was used for this cross-sectional observational study. Diabetic patients who underwent fundus photography and AL measurement between March 2017 and June 2020 were included. The fundus photographs were graded following the Early Treatment of Diabetic Retinopathy Study criteria. The study enrolled 1843 patients with diabetes (mean age: 56.9 ± 12.1 years; AL: 23.56 ± 1.12 mm), including 931 men and 912 women. Male sex was a risk factor for diabetic retinopathy (P = 0.001; odds ratio [OR] 1.5, 95% confidence interval [CI] 1.18-1.98). A higher DR prevalence was associated with shorter AL both in men (P = 0.003; OR 0.77; 95% CI 0.66-0.91) and women (P = 0.02; OR 0.83; 95% CI 0.71-0.97) after adjusting for systemic risk factors using multivariable logistic regression. There was no significant impact of sex on the relationship between AL and DR (P = 0.56). In the subset of patients with asymmetric DR, the percentage of patients whose shorter eye had a higher stage of DR was not significantly different between men and women (P = 0.20). Male sex is a risk factor for DR in a diverse safety-net hospital population. Longer AL is associated with a lower risk of DR, and this relationship is not affected by sex.

PurposeTo retrospectively evaluate the clinical data, diagnostic tests, treatments, and outcomes for dogs with corneal endothelial dystrophy (CED) and determine risk factors for CED when compared with a canine reference population.MethodsMedical records of 99 dogs (1991-2014) diagnosed with CED at the University of California Davis Veterinary Medical Teaching Hospital were reviewed and compared with 458,680 dogs comprising the general hospital population during the study period. Retrieved data included signalment, examination findings, diagnoses, treatments, and outcomes associated with CED. The exact Pearson χ2 test or exact Kruskal-Wallis test was used to compare parameters between the groups. Progression of corneal edema was assessed using 3 independent Kaplan-Meier curves, identifying clinically significant changes in corneal opacity.ResultsBoston terriers, German wirehaired pointers, and Dachshunds were overrepresented in the CED-affected group, whereas Labradors were underrepresented. Dogs older than 11 years were overrepresented in the CED-affected group, whereas intact dogs were underrepresented. Surgical intervention was performed (n = 11) based on the severity of disease and secondary complications from CED. Median time to progression of corneal edema was 1) 368 days when an at-risk eye initially without edema developed edema at a subsequent visit, 2) 701 days when there was progression from mild to marked corneal edema, and 3) 340 days when there was progression from focal to diffuse corneal edema.ConclusionsMany CED-affected dogs progress over months to years without surgical intervention, making dogs with CED a useful model for studying genetic predispositions and development of novel therapeutics for Fuchs endothelial corneal dystrophy.

PurposeTo develop and evaluate a deep learning system for differentiating between eyes with and without glaucomatous visual field damage (GVFD) and predicting the severity of GFVD from spectral domain OCT (SD OCT) optic nerve head images.DesignEvaluation of a diagnostic technology.ParticipantsA total of 9765 visual field (VF) SD OCT pairs collected from 1194 participants with and without GVFD (1909 eyes).MethodsDeep learning models were trained to use SD OCT retinal nerve fiber layer (RNFL) thickness maps, RNFL en face images, and confocal scanning laser ophthalmoscopy (CSLO) images to identify eyes with GVFD and predict quantitative VF mean deviation (MD), pattern standard deviation (PSD), and mean VF sectoral pattern deviation (PD) from SD OCT data.Main outcome measuresDeep learning models were compared with mean RNFL thickness for identifying GVFD using area under the curve (AUC), sensitivity, and specificity. For predicting MD, PSD, and mean sectoral PD, models were evaluated using R2 and mean absolute error (MAE).ResultsIn the independent test dataset, the deep learning models based on RNFL en face images achieved an AUC of 0.88 for identifying eyes with GVFD and 0.82 for detecting mild GVFD significantly (P < 0.001) better than using mean RNFL thickness measurements (AUC = 0.82 and 0.73, respectively). Deep learning models outperformed standard RNFL thickness measurements in predicting all quantitative VF metrics. In predicting MD, deep learning models based on RNFL en face images achieved an R2 of 0.70 and MAE of 2.5 decibels (dB) compared with 0.45 and 3.7 dB for RNFL thickness measurements. In predicting mean VF sectoral PD, deep learning models achieved high accuracy in the inferior nasal (R2 = 0.60) and superior nasal (R2 = 0.67) sectors, moderate accuracy in inferior (R2 = 0.26) and superior (R2 = 0.35) sectors, and lower accuracy in the central (R2 = 0.15) and temporal (R2 = 0.12) sectors.ConclusionsDeep learning models had high accuracy in identifying eyes with GFVD and predicting the severity of functional loss from SD OCT images. Accurately predicting the severity of GFVD from SD OCT imaging can help clinicians more effectively individualize the frequency of VF testing to the individual patient.

ImportanceA deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON.ObjectiveTo establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations.Design, setting, and participantsIn this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training data set. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation data sets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive data set that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis.ExposuresUse of a deep learning system.Main outcomes and measuresArea under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders.ResultsFrom a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 [12.4%], probable GON 11 046 [4.6%], unlikely GON 200 121 [83%]) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation data sets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 [46.3%] and 191 of 588 [32.3%]) and manual grading (50 of 113 [44.2%] and 183 of 538 [34.0%]) was pathologic or high myopia.Conclusions and relevanceApplication of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.

BackgroundInadequate screening of treatment-warranted retinopathy of prematurity (ROP) can lead to devastating visual outcomes. Especially in resource-poor communities, the use of an affordable, portable, and easy to use smartphone-based non-contact fundus photography device may prove useful for screening for high-risk ROP. This study evaluates the feasibility of screening for high-risk ROP using a novel smartphone-based fundus photography device, RetinaScope.MethodsRetinal images were obtained using RetinaScope on a cohort of prematurely born infants during routine examinations for ROP. Images were reviewed by two masked graders who determined the image quality, the presence or absence of plus disease, and whether there was retinopathy that met predefined criteria for referral. The agreement between image-based assessments was compared to the gold standard indirect ophthalmoscopic assessment.ResultsFifty-four eyes of 27 infants were included. A wide-field fundus photograph was obtained using RetinaScope. Image quality was acceptable or excellent in 98% and 95% of cases. There was substantial agreement between the gold standard and photographic assessment of presence or absence of plus disease (Cohen's κ = 0.85). Intergrader agreement on the presence of any retinopathy in photographs was also high (κ = 0.92).ConclusionsRetinaScope can capture digital retinal photographs of prematurely born infants with good image quality for grading of plus disease.

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

OBJECTIVE:To estimate the prevalence of ocular disease and obtain normative ocular data for free-living hummingbirds. ANIMALS STUDIED:Two hundred and sixty-three free-living, adult Hummingbirds from coastal and inland central California were studied, including Anna's (Calypte anna, n = 186) and Black-chinned (Archilochus alexandri; n = 77) hummingbirds. PROCEDURES:Slit lamp biomicroscopy and indirect ophthalmoscopy were performed on all individuals. Rebound tonometry, measurement of horizontal palpebral fissure length, and streak retinoscopy were performed on select individuals. Five conscious Anna's Hummingbirds underwent ocular imaging including fundus photography, digital slit lamp photography, and anterior segment and retinal optical coherence tomography. RESULTS:The prevalence of ocular disease in this population was 2.28%. Ocular imaging revealed a thin cornea, shallow anterior chamber, large lens, and a single central, deep convexiclivate fovea. Mean ± SD intraocular pressure was 11.21 ± 2.23 mm Hg. Mean ± SD eyelid length was 2.59 ± 0.19 mm. All eyes were emmetropic or mildly hyperopic with a mean (range) ± SD refractive error of +0.32 (-0.25 to +1) ± 0.33 diopters. CONCLUSIONS:Consistent with previous reports, these data suggest that hummingbirds have visual characteristics found in predatory and prey species, as well as a low prevalence of spontaneous ocular disease. This work provides a set of reference values and clinical findings that can be used in the future research on hummingbird vision and ocular disease. It also provides representative diagnostic images of normal birds and demonstrates that advanced ocular imaging can be performed on manually restrained hummingbirds without pharmacologic dilation.

PurposeTo investigate conjunctival and intrascleral vasculatures using anterior segment optical coherence tomography angiography (AS-OCTA) in normal eyes.DesignCross-sectional study.MethodsAS-OCTA images of the corneal limbus were acquired circumferentially using a swept-source optical coherence tomography system in 10 eyes of 10 healthy subjects. AS-OCTA flow patterns with en face maximum projection were compared between the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 μm to 1000 μm) layers. The OCTA images were also compared with fluorescein scleral angiography and indocyanine green aqueous angiography images. Quantitative parameters (vessel density, vessel length density, vessel diameter index, and fractal dimension) were compared among different locations.ResultsThe OCTA vessel patterns differed between the superficial and deep layers. The superficial-layer flow signals showed centrifugal patterns from the limbus, whereas the deep-layer flow signals showed segmental patterns. The OCTA en face images with whole signals had a similar appearance to the scleral angiography images, whereas those in the deep layer showed a similar appearance to the aqueous angiography images. In the superficial layer, only the vessel diameter index was significantly different among the locations (P = .003). In the deep layer, all 4 parameters differed significantly among the locations (P < .001 to P = .003).ConclusionsOCTA is a promising tool for evaluating conjunctival and intrascleral vasculatures. It may also help in understanding ocular surface blood flow relevant to vascular and ocular surface diseases, as well as aqueous humor outflow.

PurposeAlthough recent studies have shown that macular pigment (MP) is significantly lower in glaucoma patients, this relationship merits further investigation.MethodsThis cross-sectional study included 85 glaucoma patients and 22 controls. All subjects had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements. Intake of lutein (L) and zeaxanthin (Z) was estimated using a novel dietary screener. The Heidelberg Spectralis dual-wavelength autofluorescence (AF) technology was employed to study the relationship between MP and glaucoma. The association between MP volume and glaucoma was investigated using linear regression models accounting for potential confounding factors.ResultsGlaucoma patients had significantly worse SAP mean deviation (MD) and lower RNFL thickness in the study eye compared to control subjects (P < 0.001 for both). MP (volume) was comparable between groups (P = 0.436). In the univariable model, diagnosis of glaucoma was not associated with MP volume (R2 = 1.22%; P = 0.257). Dietary intake of L and Z was positively and significantly related to MP in the univariable (P = 0.022) and multivariable (P = 0.020) models.ConclusionsThese results challenge previous studies that reported that glaucoma is associated with low MP. Dietary habits were found to be the main predictor of MP in this sample. Further research is merited to better understand the relationship between glaucoma, MP, and visual performance in these patients.

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.

Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.

BackgroundForced eyelid closure test (FECT) is a clinical screening test developed from the original Cogan lid twitch (CLT) sign to assist in the diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and specificity of FECT compared with CLT and benchmarked to standard diagnostic tests.MethodsThis study was a retrospective chart review of 48 patients using electronic medical records of those that presented with ptosis and/or diplopia at Doheny Eye Institute, University of California, Los Angeles between February 2015 and April 2016. Patients without FECT testing were excluded. FECT and CLT results, and final diagnosis were recorded. To perform FECT, the patient was asked to squeeze his or her eyelids shut for 5-10 seconds then open quickly and fixate in primary position. The excessive upward overshoot of eyelids movement indicated a positive FECT. The test was performed by a neuro-ophthalmologist before establishing the diagnosis. Patients who had equivocal test results and/or inconclusive final diagnosis were excluded.ResultsOf the 48 patients studied, 18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG (83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48 patients, 35 patients also had a documented CLT result (72.9%). CLT was positive in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24 patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity of FECT were 94% and 91% (joint 95% confidence region: sensitivity × specificity = [0.70, 1] × [0.75, 1]). The relative true-positive fraction (rTPF) between FECT and CLT was 1.15; the relative false-positive fraction was 1.31.ConclusionsFECT is a simple clinical screening test with good sensitivity and specificity for OMG.

ObjectiveTo obtain normative data for the normal laboratory beagle cornea using high-resolution in vivo confocal microscopy (IVCM).Animals studiedSixteen eyes of eight healthy young female intact beagles.ProceduresThe central cornea was imaged using IVCM. Mixed effects linear regression was used for statistical analysis.Resultsin vivo confocal microscopy allowed detailed visualization and quantification of epithelial cells (superficial epithelial cell diameter: 43.25 ± 6.64 μm, basal cell diameter: 4.43 ± 0.67 μm), and nerve fibers (subepithelial nerve fiber diameter: 2.38 ± 0.69 μm, anterior stromal nerve fiber diameter: 16.93 ± 4.55 μm). Keratocyte density (anterior stroma 993.38 ± 134.24 cells/mm(2) , posterior stroma 789.38 ± 87.13 cells/mm(2) ) and endothelial cell density (2815.18 ± 212.59 cells/mm(2) ) were also measured.ConclusionHigh-resolution IVCM provides detailed noninvasive evaluation of the cornea in the normal laboratory beagle.

ImportanceIn strabismus, the fixating eye conveys the direction of gaze while the fellow eye points at a peripheral location in space. The stability of the eyes may be reduced by the absence of a common target.ObjectiveTo quantify the stability of eye position in strabismus and to measure variability in the ocular deviation.Design, setting, and participantsFrom 2010 to 2014, a prospective comparative case study of 25 patients with alternating exotropia with normal visual acuity in each eye and 25 control individuals was conducted in a laboratory at a tertiary eye center. A video eye tracker was used to measure the position of each eye while participants alternated fixation on the center of a cross under dichoptic conditions or scanned pictures of natural scenes.Main outcomes and measuresSpatial and temporal variability in the position of the fixating eye and the nonfixating eye in patients with strabismus and control individuals, quantified by the log area of ellipses containing 95% of eye positions or mean SDs of eye position.ResultsIn the 25 patients with strabismus, the mean (SD) age was 28 (14) years (range, 8-55 years) and the mean (SD) ocular deviation was 14.2° (5.9°) (range, 4.4°-22.4°). In the patients with strabismus, the mean position variability (1.80 log units; 95% CI, 1.66-1.93) for the deviating eye was greater than for the fixating eye (1.26 log units; 95% CI, 1.17-1.35) (P < .001). The fixating eye of patients with strabismus was more variable in position than the fixating eye of individuals without strabismus (0.98 log units; 95% CI, 0.88-1.08) (P < .005).Conclusions and relevanceIn patients with strabismus, even without amblyopia, the deviated eye is more variable in position than the fixating eye. Both eyes are less stable in position than the eyes of control individuals, which indicates that strabismus impairs the ability to fixate targets steadily. Saccades contribute to variability of the deviation angle because they are less conjugate in patients with strabismus.

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?

ObjectiveTo determine reference values, intertest correlations, and test-retest repeatability of Schirmer tear test 1 (STT-1), phenol red thread test (PRTT), tear film breakup time (TFBUT), tear osmolarity, and meibometry in healthy cats.DesignEvaluation study.Animals135 healthy domestic cats aged 0.5 to 12.8 years.ProceduresEach test was performed once in 120 cats and repeated in 40. Pearson correlation was used to assess correlation among tests. Intraclass correlation coefficients (ICCs) and 95% limits of agreement (LOA) were used to evaluate test-retest repeatability.ResultsMedian (95% central range) values were 18 mm/min (9 to 34 mm/min) for STT-1, 29 mm/15 s (15 to 37 mm/15 s) for PRTT, 12.4 seconds (9.1 to 17.7 seconds) for TFBUT, 322 mOsm/L (297 to 364 mOsm/L) for osmolarity, and 32 meibometry units (MU; 11 to 114 MU) for peak meibometry value. The STT-1 and PRTT values were positively correlated. Age was weakly associated with TFBUT and osmolarity. Meibometry measurements were higher for strips that contacted the tear film (285 MU) than for those that touched the eyelid margin only (32 MU). All ICCs were < 0.75, and 95% LOA were wide.Conclusions and clinical relevanceTear deficiency should be suspected in cats with STT-1 < 9 mm/min, PRTT < 15 mm/15 s, or TFBUT < 9 to 10 seconds. Generally poor correlation among tests suggested that thorough tear film analysis requires performance of multiple tests in concert. Relatively poor test-retest repeatability should be considered when repeated tests are used to monitor tear film dysfunction and response to treatment.

ObjectiveTo compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing.DesignProspective, single-center, case control study.ParticipantsFifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration.MethodsParticipants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected.Main outcome measuresWe assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group.ResultsFifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (

PurposeAlthough the Parks-Bielschowsky three-step test is the cornerstone of cyclovertical strabismus diagnosis, it has not been validated against an external benchmark. We evaluated the test's sensitivity in clinical diagnosis of superior oblique palsy in patients with unequivocal magnetic resonance imaging (MRI) evidence of superior oblique atrophy.MethodsA total of 73 strabismic patients were selected from a prospective MRI study because they exhibited superior oblique atrophy indicative of superior oblique denervation and thus confirmatory of superior oblique palsy. Of these, 50 patients who had no confounding factors were included for detailed study. Ocular motility data were evaluated to determine sensitivity of single and combined clinical findings in diagnosis of superior oblique palsy.ResultsMaximum mean ipsilesional superior oblique cross section was reduced to 9.6 ± 0.6 mm(2) (mean ± standard error) in superior oblique palsy, representing 52% of the 18.5 ± 0.6 mm(2) contralesional superior oblique maximum cross section and 52% of the 18.4 ± 0.4 mm(2) control maximum superior oblique cross section (P < 0.001). Of the 50 patients, 35 (70%) with superior oblique atrophy fulfilled the entire three-step test. In 14 (28%) patients two steps were fulfilled; in 1 patient (2%), only one step. Affected superior oblique cross section was similar in orbits that fulfilled the three-step test (9.8 ± 0.9 mm(2)) and those that did not (9.1 ± 0.7 mm(2); P = 0.58).ConclusionsThe complete three-step test fails to detect 30% of cases of superior oblique atrophy. Often only two of three steps are positive in superior oblique palsy.

BackgroundSuperior rectus transposition with or without medial rectus recession has been advocated for the treatment of abducens nerve palsy and esotropic Duane syndrome. Early reports have focused mainly on postoperative ocular alignment, but there is concern that superior rectus transposition may induce torsional misalignment. The purpose of this study was to evaluate torsional outcomes after superior rectus transposition surgery using prospective preoperative and postoperative torsional assessments.MethodsProspective measurements were performed on all patients undergoing superior rectus transposition. Preverbal infants were assessed using fundus torsion evaluating the position of the fovea relative to the optic nerve; older children/adults underwent double Maddox rod (DMR) assessment of torsion.ResultsA total of 11 subjects met the study inclusion criteria. The etiology of strabismus was an abducens nerve palsy (n = 7) or Duane syndrome (n = 4). For the subjects evaluated by fundus torsion (n = 4), there was no significant change in torsion for 3 (75%). For those subjects undergoing DMR (n = 7), there was a significant change in subjective torsion (4.7 ± 3.8°excyclotorsion vs 0.0° ± 5.0° excyclotorsion; P = 0.004). Esotropic deviation improved significantly for all subjects (39(Δ) ± 23(Δ) vs 6.5(Δ) ± 13(Δ); P = 0.001) and no significant mean vertical deviation postoperatively, although 1 patient had a clinically significant postoperative hypertropia measuring 14(Δ). Abduction also improved significantly (-4.2 ± 0.9 vs -2.8 ± 1, P = 0.0001).ConclusionsIn this patient series, superior rectus transposition with medial rectus recession did not have clinically significant induction of torsional diplopia as a result of the procedure.

ObjectiveTo evaluate the ability of a binocular automated pupillograph to discriminate healthy subjects from those with glaucoma.DesignCross-sectional observational study.ParticipantsBoth eyes of 116 subjects, including 66 patients with glaucoma in at least 1 eye and 50 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Eyes were classified as glaucomatous by repeatable abnormal standard automated perimetry (SAP) or progressive glaucomatous changes on stereophotographs.MethodsAll subjects underwent automated pupillography using the RAPDx pupillograph (Konan Medical USA, Inc., Irvine, CA).Main outcome measuresReceiver operating characteristic (ROC) curves were constructed to assess the diagnostic ability of pupil response parameters to white, red, green, yellow, and blue full-field and regional stimuli. A ROC regression model was used to investigate the influence of disease severity and asymmetry on diagnostic ability.ResultsThe largest area under the ROC curve (AUC) for any single parameter was 0.75. Disease asymmetry (P

ObjectiveTo evaluate changes in peripapillary and macular choroidal thickness and volume after the water-drinking test (WDT) using swept-source optical coherence tomography (SS OCT).DesignProspective, cross-sectional, observational study.ParticipantsFifty-six eyes of 28 healthy volunteers.MethodsParticipants underwent a 3-dimensional optic disc and macula scanning protocol with a prototype SS OCT (Topcon, Inc., Tokyo, Japan) at baseline and 15, 30, 45, and 120 minutes after the start of the WDT. The WDT consisted of drinking 1000 ml of water within 5 minutes. Objective measurements of the choroid were obtained with automated segmentation of the choroidal boundaries.Main outcome measuresChoroidal thickness and volume.ResultsMean age ± standard deviation of participants was 35.6 ± 9.1 years. Intraocular pressure (IOP) increased from 14.9 ± 2.7 mmHg at baseline to a peak of 16.8 ± 3.0 mmHg 15 minutes after the WDT (P

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

UnlabelledAIMS; It is well established that glaucoma results in a thinning of the inner retina. To investigate whether the outer retina is also involved, ultrahigh-resolution retinal imaging techniques were utilised.MethodsEyes from 10 glaucoma patients (25-78 years old), were imaged using three research-grade instruments: (1) ultrahigh-resolution Fourier-domain optical coherence tomography (UHR-FD-OCT), (2) adaptive optics (AO) UHR-FD-OCT and (3) AO-flood illuminated fundus camera (AO-FC). UHR-FD-OCT and AO-UHR-FD-OCT B-scans were examined for any abnormalities in the retinal layers. On some patients, cone density measurements were made from the AO-FC en face images. Correlations between retinal structure and visual sensitivity were measured by Humphrey visual-field (VF) testing made at the corresponding retinal locations.ResultsAll three in vivo imaging modalities revealed evidence of outer retinal changes along with the expected thinning of the inner retina in glaucomatous eyes with VF loss. AO-UHR-FD-OCT images identified the exact location of structural changes within the cone photoreceptor layer with the AO-FC en face images showing dark areas in the cone mosaic at the same retinal locations with reduced visual sensitivity.ConclusionLosses in cone density along with expected inner retinal changes were demonstrated in well-characterised glaucoma patients with VF loss.

PurposeTo study the integrity of inner and outer retinal layers in patients with various types of optic neuropathy by using high-resolution imaging modalities.MethodsThree high-resolution imaging systems constructed at the University of California Davis were used to acquire retinal images from patients with optic neuropathy: (1) adaptive optics (AO)-flood-illuminated fundus camera, (2) high-resolution Fourier domain optical coherence tomography (FDOCT), and (3) adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). The AO fundus camera provides en face images of photoreceptors whereas cross-sectional images (B-scans) of the retina are obtained with both FDOCT and AO-FDOCT. From the volumetric FDOCT data sets, detailed thickness maps of a three-layer complex consisting of the nerve fiber (NF), ganglion cell (GC), and inner plexiform (IP) layers were created. The number of visible cones in the en face images of photoreceptors was then compared with visual sensitivity maps from Humphrey visual field (HVF; Carl Zeiss Meditec, Inc., Dublin, CA) testing, as well as FDOCT and AO-FDOCT images, including the thickness maps of the NF-GC-IP layer complex. Five types of optic neuropathy were studied: (1) optic neuritis with multiple sclerosis (MS), (2) idiopathic intracranial hypertension (pseudotumor cerebri), (3) nonarteritic anterior ischemic optic neuropathy (NAION), (4) optic nerve head drusen with NAION, and (5) systemic lupus erythematosus with MS and arthritis.ResultsWith permanent visual field loss and thinning of the NF-GC-IP layer complex, cone photoreceptors showed structural changes, making them less reflective, which caused the appearance of dark spaces in the en face images (hence, reduced number of visible cones) and indistinct outer retinal layers in OCT images. However, when the visual field loss was only transient, with a normal NF-GC-IP layer complex, there were no detectable abnormalities in cone photoreceptors (i.e., they were densely packed and had distinct photoreceptor layering in the OCT images).ConclusionsCone photoreceptors show structural changes when there is permanent damage to overlying inner retinal layers. There was a positive relation between the thickness of the three-layer inner retinal complex, visual sensitivity, and integrity of the cone mosaic.

PurposeTo relate in vivo microscopic retinal changes to visual function in patients who have various forms of retinal dystrophy.MethodsThe UC Davis Adaptive Optics (AO) fundus camera was used to acquire in vivo retinal images at the cellular level. Visual function tests consisting of visual fields, multifocal electroretinography (mfERG), and contrast sensitivity were measured in all subjects by using stimuli that were coincident with areas imaged. Five patients with different forms of retinal dystrophy and three control subjects were recruited. Cone densities were quantified for all retinal images.ResultsIn all images of diseased retinas, there were extensive areas of dark space between groups of photoreceptors, where no cone photoreceptors were evident. These irregular features were not seen in healthy retinas, but were apparent in patients with retinal dystrophy. There were significant correlations between functional vision losses and the extent to which these irregularities, quantified by cone density, occurred in retinal images.ConclusionsAO fundus imaging is a reliable technique for assessing and quantifying the changes in the photoreceptor layer as disease progresses. Furthermore, this technique can be useful in cases where visual function tests provide borderline or ambiguous results, as it allows visualization of individual photoreceptors.