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Binocular vision anomalies are major causes of asthenopia symptoms, particularly among the younger population. This study aimed to report the clinical characteristics of Sudanese patients with binocular disorders who attended the orthoptic clinic at Al-Neelain Eye Hospital. In this retrospective hospital-based study, we analyzed data from 304 patients with binocular vision anomalies who visited the orthoptic clinic between October 2020 and June 2021. We collected information on demographics, symptoms, and eye tests such as visual acuity (VA), refractive error (RE), angle of deviation, and the assessment of fusional vergence. Our findings indicated that exophoria was the most common binocular vision anomaly, affecting 79.8% of males and 71.6% of females (p=0.731). Children between 6 and 17 years old showed the highest prevalence of exophoria (75.9%) (p=0.0001). Among patients with exophoria, 100% reported itching associated with tearing during fixation, while 89.5% experienced difficulty in fixation. Refractive error varied by the type of binocular vision disorders (p=0.0001), with higher hyperopia observed in cases of unilateral esotropia and alternate esotropia (+3.571±1.238 D and +3.023±1.553 D, respectively). Positive fusional vergence (PFV) differed by types of binocular vision disorders (p=0.0001) with high PFV in esophoria (18.063±6.848∆) compared to low PFV in exophoria (12.80±5.313∆). The most common types of exophoria were convergence weakness exophoria (45.39%), followed by convergence insufficiency (20.39%). The study concluded that exophoria was the most common binocular vision anomaly among Sudanese patients, with convergence weakness and convergence insufficiency being the predominant anomalies. Headache was commonly prevalent among patients with binocular vision problems. Higher hyperopia was found in esodeviation, while low PFV was associated with exodeviation.

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Purpose: To develop a severity classification for macular telangiectasia type 2 (MacTel) disease using multimodal imaging. Design: An algorithm was used on data from a prospective natural history study of MacTel for classification development. Subjects: A total of 1733 participants enrolled in an international natural history study of MacTel. Methods: The Classification and Regression Trees (CART), a predictive nonparametric algorithm used in machine learning, analyzed the features of the multimodal imaging important for the development of a classification, including reading center gradings of the following digital images: stereoscopic color and red-free fundus photographs, fluorescein angiographic images, fundus autofluorescence images, and spectral-domain (SD)-OCT images. Regression models that used least square method created a decision tree using features of the ocular images into different categories of disease severity. Main Outcome Measures: The primary target of interest for the algorithm development by CART was the change in best-corrected visual acuity (BCVA) at baseline for the right and left eyes. These analyses using the algorithm were repeated for the BCVA obtained at the last study visit of the natural history study for the right and left eyes. Results: The CART analyses demonstrated 3 important features from the multimodal imaging for the classification: OCT hyper-reflectivity, pigment, and ellipsoid zone loss. By combining these 3 features (as absent, present, noncentral involvement, and central involvement of the macula), a 7-step scale was created, ranging from excellent to poor visual acuity. At grade 0, 3 features are not present. At the most severe grade, pigment and exudative neovascularization are present. To further validate the classification, using the Generalized Estimating Equation regression models, analyses for the annual relative risk of progression over a period of 5 years for vision loss and for progression along the scale were performed. Conclusions: This analysis using the data from current imaging modalities in participants followed in the MacTel natural history study informed a classification for MacTel disease severity featuring variables from SD-OCT. This classification is designed to provide better communications to other clinicians, researchers, and patients. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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Objective: To demonstrate that electronic health record (EHR) data can be used in an automated approach to evaluate cataract surgery outcomes. Design: Retrospective analysis. Subjects: Resident and faculty surgeons. Methods: Electronic health record data were collected from cataract surgeries performed at the Johns Hopkins Wilmer Eye Institute, and cases were categorized into resident or attending as primary surgeon. Preoperative and postoperative visual acuity (VA) and unplanned return to operating room were extracted from the EHR. Main Outcome Measures: Postoperative VA and reoperation rate within 90 days. Results: This study analyzed 14 537 cataract surgery cases over 32 months. Data were extracted from the EHR using an automated approach to assess surgical outcomes for resident and attending surgeons. Of 337 resident surgeries with both preoperative and postoperative VA data, 248 cases (74%) had better postoperative VA, and 170 cases (51%) had more than 2 lines improvement. There was no statistical difference in the proportion of cases with better postoperative VA or more than 2 lines improvement between resident and attending cases. Attending surgeons had a statistically greater proportion of cases with postoperative VA better than 20/40, but this finding has to be considered in the context that, on average, resident cases started out with poorer baseline VA.A multivariable regression model of VA outcomes vs. resident/attending status that controlled for preoperative VA, patient age, American Society of Anesthesiologists (ASA) score, and estimated income found that resident status, preoperative VA, patient age, ASA score, and estimated income were all significant predictors of VA. The rate of unplanned return to the operating room within 90 days of cataract surgery was not statistically different between resident (1.8%) and attending (1.2%) surgeons. Conclusions: This study demonstrates that EHR data can be used to evaluate and monitor surgical outcomes in an ongoing way. Analysis of EHR-extracted cataract outcome data showed that preoperative VA, ASA classification, and attending/resident status were important in predicting postoperative VA outcomes. These findings suggest that the utilization of EHR data could enable continuous assessment of surgical outcomes and inform interventions to improve resident training. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Objective: To examine the data quality and usability of visual acuity (VA) data extracted from an electronic health record (EHR) system during ophthalmology encounters and provide recommendations for consideration of relevant VA end points in retrospective analyses. Design: Retrospective, EHR data analysis. Participants: All patients with eyecare office encounters at any 1 of the 9 locations of a large academic medical center between August 1, 2013, and December 31, 2015. Methods: Data from 13 of the 21 VA fields (accounting for 93% VA data) in EHR encounters were extracted, categorized, recoded, and assessed for conformance and plausibility using an internal data dictionary, a 38-item listing of VA line measurements and observations including 28 line measurements (e.g., 20/30, 20/400) and 10 observations (e.g., no light perception). Entries were classified into usable and unusable data. Usable data were further categorized based on conformance to the internal data dictionary: (1) exact match; (2) conditional conformance, letter count (e.g., 20/30+2 - 3); (3) convertible conformance (e.g., 5/200 to 20/800); (4) plausible but cannot be conformed (e.g., 5/400). Data were deemed unusable when they were not plausible. Main Outcome Measures: Proportions of usable and unusable VA entries at the overall and subspecialty levels. Results: All VA data from 513 036 encounters representing 166 212 patients were included. Of the 1 573 643 VA entries, 1 438 661 (91.4%) contained usable data. There were 1 196 720 (76.0%) exact match (category 1), 185 692 (11.8%) conditional conformance (category 2), 40 270 (2.6%) convertible conformance (category 3), and 15 979 (1.0%) plausible but not conformed entries (category 4). Visual acuity entries during visits with providers from retina (17.5%), glaucoma (14.0%), neuro-ophthalmology (8.9%), and low vision (8.8%) had the highest rates of unusable data. Documented VA entries with providers from comprehensive eyecare (86.7%), oculoplastics (81.5%), and pediatrics/strabismus (78.6%) yielded the highest proportions of exact match with the data dictionary. Conclusions: Electronic health record VA data quality and usability vary across documented VA measures, observations, and eyecare subspecialty. We proposed a checklist of considerations and recommendations for planning, extracting, analyzing, and reporting retrospective study outcomes using EHR VA data. These are important first steps to standardize analyses enabling comparative research.

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Purpose: Pathogenic variants in FAM161A are the most common cause of retinitis pigmentosa in Israel. Two founder pathogenic variants explain the vast majority of cases of Jewish origin, 1 being a nonsense variant (p.Arg523∗). The aim of this study was to generate a knock-in (KI) mouse model harboring the corresponding p.Arg512∗ pathogenic variant and characterize the course of retinal disease. Design: Experimental study of a mouse animal model. Subjects/Participants/Controls: A total of 106 Fam161a knock-in mice and 29 wild-type mice with C57BL/6J background particiapted in this study. Methods: Homozygous Fam161a p.Arg512∗ KI mice were generated by Cyagen Biosciences. Visual acuity (VA) was evaluated using optomotor tracking response and retinal function was assessed by electroretinography (ERG). Retinal structure was examined in vivo using OCT and fundus autofluorescence imaging. Retinal morphometry was evaluated by histologic and immunohistochemical (IHC) analyses. Main Outcome Measures: Visual and retinal function assessments, clinical imaging examinations, quantitative histology, and IHC studies of KI as compared with wild-type (WT) mice retinas. Results: The KI model was generated by replacing 3 bp, resulting in p.Arg512∗. Homozygous KI mice that had progressive loss of VA and ERG responses until the age of 18 months, with no detectable response at 21 months. OCT showed complete loss of the outer nuclear layer at 21 months. Fundus autofluorescence imaging revealed progressive narrowing of blood vessels and formation of patchy hyper-autofluorescent and hypo-autofluorescent spots. Histologic analysis showed progressive loss of photoreceptor nuclei. Immunohistochemistry staining showed Fam161a expression mainly in photoreceptors cilia and the outer plexiform layer (OPL) in WT mice retinas, whereas faint expression was evident mainly in the cilia and OPL of KI mice. Conclusions: The Fam161a - p.Arg512∗ KI mouse model is characterized by widespread retinal degeneration with relatively slow progression. Surprisingly, disease onset is delayed and progression is slower compared with the previously reported knock-out model. The common human null mutation in the KI mouse model is potentially amenable for correction by translational read-through-inducing drugs and by gene augmentation therapy and RNA editing, and can serve to test these treatments as a first step toward possible application in patients. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Purpose: To identify baseline ocular and systemic factors associated with central subfield thickness (CST) fluctuations in patients with diabetic macular edema (DME) using data from Diabetic Retinopathy Clinical Research Protocols T and V. Design: Post hoc analysis of clinical trial databases. Subjects: Patients in Protocols T and V. Methods: The standard deviation (SD) of all recorded CSTs for each patient during each Protocol's study period was calculated. The CST SD (corresponding to CST fluctuations) for each patient was analyzed against baseline ocular and systemic factors using linear regression analyses. Each Protocol was analyzed separately. Main Outcome Measures: Factors associated with CST fluctuations. Results: A total of 1197 eyes of 1197 subjects were included. In Protocol T (559 eyes, mean CST SD was 56.4 ± 35.1 microns), using multivariate linear regression analysis, baseline urine albumin/creatine ratio (for every 1000 mg/g, CST point estimate 3.50, 95% confidence interval [CI] 0.58 to 6.43, P = 0.0190), and baseline CST (for every 10 microns, 0.87, 95% CI 0.58 to 1.16, P < 0.0001) were positively associated with CST fluctuations. Baseline visual acuity (for every 10 ETDRS letters, -9.52, 95% CI -11.89 to -7.15, P < 0.0001) was negatively associated with CST fluctuations. In Protocol V (638 eyes, mean CST SD 36.6 ± 28.4 microns), gender (female, 2.18, 95% CI 0.30 to 4.06, P = 0.0227), baseline CST (for every 10 microns, 2.51, 95% CI 2.21 to 2.82, P < 0.0001), systolic blood pressure (for every 1 mm of mercury, 0.11, 95% CI 0.01 to 0.21, P = 0.0261), and observation with deferred anti-VEGF injections (5.04, 95% CI 2.51 to 7.58, P < 0.0001) were positively associated with CST fluctuations. Type 2 diabetes (-7.37, 95% CI -13.64 to -1.11, P = 0.0209) and prompt anti-VEGF injections (-6.51, 95% CI -9.07 to -3.96, P < 0.0001) were negatively associated with CST fluctuations. Conclusions: Worse visual acuity at baseline, baseline renal disease, hypertension, female gender, type 1 diabetes, and delayed anti-VEGF treatment may be associated with increased CST fluctuations in patients with DME. Addressing these parameters may limit CST fluctuations and help identify patients requiring more frequent monitoring or treatment.

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Purpose: To evaluate efficacy and vision with 2 prototype myopia control soft contact lenses with noncoaxial ring-focus designs (for enhancing efficacy [EE] and enhancing vision [EV]) compared with dual-focus (DF) and single-vision (SV) designs. Design: Multicenter, 6-month, randomized, controlled, double-masked clinical trial. Participants: One hundred ninety-nine myopic (-0.75 diopters [D] to -4.50 D) children aged 7 to 12 years. Methods: Participants were randomized with stratification into myopia control (EE, EV, or DF) or SV arms at 9 clinical sites in 3 countries. Postcycloplegia axial length (AL) and spherical equivalent autorefraction (SECAR) were measured at baseline and 26 weeks. Axial length was also measured without cycloplegia at baseline, 1, 4, 13, and 26 weeks. Progression was analyzed using linear mixed models by intention-to-treat population. Visual acuity (VA) and vision quality were monitored. Main Outcome Measures: Axial elongation, change in SECAR. Results: A total of 185 subjects completed the study (n = 44, 49, 45, and 47 for EE, EV, DF, and SV, respectively). There were no serious/significant ocular adverse events. After 26 weeks, EE, EV, and DF all had statistically significantly less axial elongation than SV (unadjusted mean [standard deviation]: EE, 0.079 [0.125]; EV, 0.119 [0.101]; DF, 0.135 [0.117]; SV; 0.189 [0.121] mm). The estimated least-square mean (LSM) differences (adjusted 95% confidence interval) compared with SV were -0.105 (-0.149, -0.062), -0.063 (-0.106, -0.020), and -0.056 (-0.100, -0.013) mm for EE, EV, and DF, respectively. Enhancing efficacy alone had statistically significantly less progression of SECAR than SV (EE: -0.12 [0.27] D vs. SV: -0.35 [0.33] D; LSM difference: 0.22 D [0.09, 0.35]). Enhancing efficacy also had statistically significantly less axial elongation than DF (-0.049 mm [-0.093, -0.004]). Changes in AL and SECAR of EV and DF were not statistically different. All 3 myopia control lenses had mean VA close to 0.00 logarithm of the minimum angle of resolution (logMAR) with estimated 95% upper confidence limits <0.10 logMAR. Enhancing efficacy and DF produced similar reports of halos but more than EV and SV. Conclusions: The prototype contact lenses met the design intent; EE was more efficacious in slowing axial elongation than DF with comparable vision performance, whereas EV produced comparable efficacy to DF with similar vision performance to SV.

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Purpose: To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. Design: Prospective, cross-sectional, observational study. Participants: One hundred and forty-four eyes of 114 patients with diabetes. Methods: Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. Main Outcome Measures: The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. Results: The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102-1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001-1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. Conclusions: The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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Purpose: To assess the differences in rod-mediated dark adaptation (RMDA) between different grades of age-related macular degeneration (AMD) severity using an OCT-based criterion compared with those of AMD severity using the Beckman color fundus photography (CFP)-based classification and to assess the association between the presence of subretinal drusenoid deposits (SDDs) and RMDA at different grades of AMD severity using an OCT-based classification. Design: Cross-sectional study. Participants: Participants from the Northern Ireland Sensory Ageing study (Queen's University Belfast). Methods: Complete RMDA (rod-intercept time [RIT]) data, CFP, and spectral-domain OCT images were extracted. Participants were stratified into 4 Beckman groups (omitting late-stage AMD) and 3 OCT-based groups. The presence and stage of SDDs were identified using OCT. Main Outcome Measures: Rod-intercept time data (age-corrected). Results: Data from 459 participants (median [interquartile range] age, 65 [59-71] years) were stratified by both the classifications. Subretinal drusenoid deposits were detected in 109 eyes. The median (interquartile range) RMDA for the Beckman classification (Beckman 0-3, with 3 being intermediate age-related macular degeneration [iAMD]) groups was 6.0 (4.5-8.7), 6.6 (4.7-10.5), 5.7 (4.4-7.4), and 13.2 (6-21.1) minutes, respectively. OCT classifications OCT0-OCT2 yielded different median (interquartile range) values: 5.8 (4.5-8.5), 8.4 (5.2-13.3), and 11.1 (5.3-20.1) minutes, respectively. After correcting for age, eyes in Beckman 3 (iAMD) had statistically significantly worse RMDA than eyes in the other Beckman groups (P ≤ 0.005 for all), with no statistically significant differences between the other Beckman groups. Similarly, after age correction, eyes in OCT2 had worse RMDA than eyes in OCT0 (P ≤ 0.001) and OCT1 (P < 0.01); however, there was no statistically significant difference between eyes in OCT0 and eyes in OCT1 (P = 0.195). The presence of SDDs was associated with worse RMDA in OCT2 (P < 0.01) but not in OCT1 (P = 0.285). Conclusions: Eyes with a structural definition of iAMD have delayed RMDA, regardless of whether a CFP- or OCT-based criterion is used. In this study, after correcting for age, the RMDA did not differ between groups of eyes defined to have early AMD or normal aging, regardless of the classification. The presence of SDDs has some effect on RMDA at different grades of AMD severity.

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Age-related macular degeneration (AMD) is the leading cause of blindness for the elderly in high-income countries. Although multivitamin antioxidant nutrients can slow the progression of intermediate "dry" or nonneovascular AMD, no treatment can halt or reverse any stage of dry disease. Multiple biologic pathways have been implicated in AMD pathobiology, including the complement pathway. These pathways have been targeted by various approaches in clinical trials. To date, no treatment has reached their prespecified primary end point in 2 phase III trials, a requirement by the US Food and Drug Administration for a new drug approval. Here, we describe perspectives on the failures and possible successes of various clinical trials that will guide further investigation. These perspectives will also discuss clinical trial design issues to consider in future investigations, and how recent insights into AMD pathobiology might both provide additional explanation for trials not reaching the prespecified primary end points and offer direction for identifying prioritized treatment targets.

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Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed "exudative" or "neovascular AMD," or retinal pigment epithelium (RPE) cell and photoreceptor death, termed "geographic atrophy" (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with GA. These approaches include reduction of oxidative stress, modulation of the visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue-derived cells, and RPE replacement. Despite active investigation in this area and significant promise based on preclinical studies, many clinical studies have not yielded successful results. We discuss selected past and current neuroprotection trials for AMD, highlight the lessons learned from these past studies, and discuss our perspective regarding remaining questions that must be answered before neuroprotection can be successfully applied in the field of AMD research.

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Purpose: The foveal avascular zone (FAZ) has been reported to decrease after anti-VEGF injections in diabetic macular edema (DME) in the long term. This study aimed to present the changes in swept-source OCT angiography after vitrectomy in patients with DME. Design: Retrospective interventional study. Participants: Thirty-five eyes were included (mean age: 62 years). Methods: Patients were followed for 12 months after vitrectomy with internal limiting membrane peeling for DME. Main Outcome Measures: The following parameters were measured: central retinal thickness (CRT), central choroidal thickness, superficial FAZ, deep FAZ (dFAZ), and vessel density in the superficial and deep retinal layers (dVD). Results: The CRT and superficial FAZ significantly decreased after surgery (401 µm-338 µm; P < 0.00, 401 µm-293 µm; P < 0.001, respectively). Initial visual acuity (VA) improved from 20/160 (0.97 logarithm of the minimum angle of resolution [LogMAR]) to 20/80 (0.62 LogMAR) (P < 0.001). The vessel density in the superficial retinal layers rate was 42.3% and decreased after surgery, reaching 41.6% at the end of the follow-up. The dVD rate 1 week after surgery was 28.9% and remained stable throughout the observation period. The most important prognostic factors for the final VA were preoperative VA and preoperative CRT, while the dFAZ and dVD at the time of edema resolution also correlated with the final VA. Conclusions: The superficial FAZ decreases after vitrectomy, which might indicate that vitrectomy has a protective effect on DME, similar to anti-VEGF injections. Prognostic factors for better final functional results are better initial VA and lower CRT before vitrectomy, in addition to a lower dFAZ diameter and a higher dVD at the moment of edema resolution. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Purpose: To validate and assess user satisfaction and usability of the New York University (NYU) Langone Eye Test application, a smartphone-based visual acuity (VA) test. Design: Mixed-methods cross-sectional cohort study. Participants: Two hundred forty-four eyes of 125 participants were included. All participants were adults 18 years of age or older. Participants' eyes with a VA of 20/400 (1.3 logarithm of the minimum angle of resolution [logMAR]) or worse were excluded. Methods: Patients were tested using the clinical standard Rosenbaum near card and the NYU Langone Eye Test application on an iPhone and Android device. Each test was performed twice to measure reliability. Ten patients were selected randomly for subsequent semistructured qualitative interviews with thematic analysis. Main Outcome Measures: Visual acuity was the parameter measured. Bland-Altman analysis was used to measure agreement between the results of the NYU Langone Eye Test application and Rosenbaum card, as well as test-retest reliability of each VA. The correlation between results was calculated using the intraclass correlation coefficient. Satisfaction survey and semistructured interview questions were developed to measure usability and acceptability. Results: Bland-Altman analysis revealed an agreement between the application and the Rosenbaum near card of 0.017 ± 0.28 logMAR (iPhone) and 0.009 ± 0.29 logMAR (Android). The correlation between the application and the Rosenbaum near card was 0.74 for both the iPhone and Android. Test-retest reliability was 0.003 ± 0.22 logMAR (iPhone), 0.01 ± 0.25 logMAR (Android), and 0.01 ± 0.23 logMAR (Rosenbaum card). Of the 125 participants, 97.6% found the application easy to use, and 94.3% were overall satisfied with the application. Thematic analysis yielded 6 key themes: (1) weaknesses of application, (2) benefits of the application, (3) tips for application improvement, (4) difficulties faced while using the application, (5) ideal patient for application, and (6) comparing application with traditional VA testing. Conclusions: The NYU Langone Eye Test application is a user-friendly, accurate, and reliable measure of near VA. The application's integration with the electronic health record, accessibility, and easy interpretation of results, among other features, make it ideal for telemedicine use.

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Purpose: To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the centrosomal protein 290 (CEP290) gene. Design: Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial. Participants: A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15-41 years) selected for detailed analyses. Medical histories of 4 participants were consistent with congenital binocular blindness, whereas 1 participant showed evidence of spatial vision in early life that was later lost. Intervention: Participants received a single intravitreal injection of sepofarsen (160 or 320 µg) into the study eye. Main Outcome Measures: Full-field stimulus testing (FST), visual acuity (VA), and transient pupillary light reflex (TPLR) were measured at baseline and for 3 months after the injection. Results: All 5 participants with LP vision demonstrated severely abnormal FST and TPLR findings. At baseline, FST threshold estimates were 0.81 and 1.0 log cd/m2 for control and study eyes, respectively. At 3 months, study eyes showed a large mean improvement of -1.75 log versus baseline (P < 0.001), whereas untreated control eyes were comparable with baseline. Blue minus red FST values were not different than 0 (P = 0.59), compatible with cone mediation of remnant vision. At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline. Specialized tests performed in 1 participant confirmed and extended the standardized results from all 5 participants. Conclusions: By subjective and objective evidence, intravitreal sepofarsen provides improvement of light sensitivity for individuals with LP vision. However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity.

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Purpose: To examine the association of baseline choroidal sublayers metrics with the risk of diabetic retinopathy (DR) progression over 2 years, with adjustment for confounding factors that affect choroidal measurements. Design: Prospective, observational cohort study. Participants: One hundred three eyes from 62 patients with diabetes mellitus (DM). Methods: Patients were followed up at 6-month intervals for at least 2 years. Choroidal metrics including choroidal area, choroidal thickness (CT), and choroidal vascularity index were measured for both (1) the choriocapillaris plus Sattler's layer and (2) the Haller's layer within the subfoveal and parafoveal region. Cox proportional models were constructed to estimate the relationship between baseline choroidal metrics and DR progression, adjusted for intereye correlation, established risk factors (i.e., duration of DM, glycated hemoglobin [HbA1c] level, body mass index [BMI], use of insulin, and mean arterial blood pressure [MABP]) and confounding factors of choroidal measurements (i.e., age and axial length). Additional predictive value of choroidal metrics was assessed using the C-statistic. Main Outcome Measures: Hazard ratios (HRs) calculated by Cox proportional hazards model to demonstrate the associations between baseline choroidal metrics and DR progression. Results: After adjusting for age, axial length, and intereye correlation, choroidal metrics in Haller's layer at baseline that were associated with a higher risk of DR progression included increases in subfoveal choroidal area (HR, 2.033; 95% confidence interval [CI], 1.179-3.505; P = 0.011), subfoveal plus parafoveal choroidal area (HR, 1.909; 95% CI, 1.096-3.326; P = 0.022), subfoveal CT (HR, 2.032; 95% CI, 1.181-3.498; P = 0.010), and subfoveal plus parafoveal CT (HR, 1.908; 95% CI, 1.097-3.319; P = 0.022). These associations remained statistically significant after additionally adjusting for duration of DM, HbA1c level, BMI, use of insulin, and MABP. Addition of these choroidal metrics significantly improved the discrimination for DR progression when compared with established risk factors alone (e.g., duration of DM and HbA1c; increase in C-statistic ranged from 8.08% to 9.67% [P < 0.05]). Conclusions: Eyes with a larger choroidal area and CT in Haller's layer at baseline were associated with a higher risk of DR progression over 2 years.

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Purpose: To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC). Design: Retrospective cohort study. Participants: A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded. Methods: All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed. Main Outcome Measures: The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate). Results: A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients' backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (-0.06 vs. -0.008, P = 0.07, 12 months; -0.06 vs. -0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24-7.89; P < 0.001). Conclusions: The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.

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Purpose: To report a case of acute neovascular glaucoma with partial synechial angle closure secondary to central retinal vein occlusion that underwent gonioscopy-assisted transluminal trabeculotomy as well as near-monthly anti-vascular endothelial growth factor (VEGF) injections and panretinal photocoagulation (PRP) treatments. Observations: Nine months after GATT, the patient had achieved intraocular pressure control on no medications. However, she was lost to follow up for 4 months and received no anti-VEGF or PRP during that time; she re-presented with acute NVG and complete synechial closure, and ultimately underwent aqueous shunt implantation. Conclusions and Importance: To our knowledge, this is the first reported attempt of an ab interno angle surgery to successfully restore aqueous outflow through the conventional outflow pathway in an eye with acute NVG and partial synechial angle closure. We posit that this can be an effective approach to achieve IOP control in NVG with at least partially open angles, as long as sufficient anti-neovascular treatments are administered until the underlying neovascular drive achieves quiescence.

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Childhood vision screening programmes in Europe differ by age, frequency and location at which the child is screened, and by the professional who performs the test. The aim of this study is to compare the cost-effectiveness for three countries with different health care structures. We developed a microsimulation model of amblyopia. The natural history parameters were calibrated to a Dutch observational study. Sensitivity, specificity, attendance, lost to follow-up and costs in the three countries were based on the EUSCREEN Survey. Quality adjusted life-years (QALYs) were calculated using assumed utility loss for unilateral persistent amblyopia (1%) and bilateral visual impairment (8%). We calculated the cost-effectiveness of screening (with 3.5% annual discount) by visual acuity measurement at age 5 years or 4 and 5 years in the Netherlands by nurses in child healthcare centres, in England and Wales by orthoptists in schools and in Romania by urban kindergarten nurses. We compared screening at various ages and with various frequencies. Assuming an amblyopia prevalence of 36 per 1,000 children, the model predicted that 7.2 cases of persistent amblyopia were prevented in the Netherlands, 6.6 in England and Wales and 4.5 in Romania. The cost-effectiveness was €24,159, €19,981 and €23,589, per QALY gained respectively, compared with no screening. Costs/QALY was influenced most by assumed utility loss of unilateral persistent amblyopia. For all three countries, screening at age 5, or age 4 and 5 years were optimal. Despite differences in health care structure, vision screening by visual acuity measurement seemed cost-effective in all three countries.

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BACKGROUND: Although visual dysfunction is one of the most common non-motor symptoms among patients with Parkinson's disease (PD), it is not known whether visual impairment (VI) predates the onset of clinical PD. Therefore, we aim to examine the association of VI with the future development of PD in the UK Biobank Study. METHODS: The UK Biobank Study is one of the largest cohort studies of health, enrolling over 500,000 participants aged 40-69 years between 2006 and 2010 across the UK. VI was defined as a habitual distance visual acuity (VA) worse than 0·3 logarithm of the minimum angle of resolution (LogMAR) in the better-seeing eye. Incident cases of PD were determined by self report data, hospital admission records or death records, whichever came first. Multivariable Cox proportional hazard regression models were used to investigate the association between VI and the risk of incident PD. FINDINGS: A total of 117,050 participants were free of PD at the baseline assessment. During the median observation period of 5·96 (IQR: 5·77-6·23) years, PD occurred in 222 (0·19%) participants. Visually impaired participants were at a higher risk of developing PD than non-VI participants (p < 0·001). Compared with the non-VI group, the adjusted hazard ratio was 2·28 (95% CI 1·29-4·05, p = 0·005) in the VI group. These results were consistent in the sensitivity analysis, where incident PD cases diagnosed within one year after the baseline assessment were excluded. INTERPRETATION: This cohort study found that VI was associated with an increased risk of incident PD, suggesting that VI may serve as a modifiable risk factor for prevention of future PD.

RESUMEN

Purpose: The recent exponential growth in teleophthalmology has been limited in part by the lack of a validated method to measure visual acuity (VA) remotely. We investigated the validity of a self-administered Early Treatment Diabetic Retinopathy Study (ETDRS) home VA test. We hypothesized that a home VA test with a printout ETDRS chart is equivalent to a standard technician-administered VA test in clinic. Design: Prospective cohort study. Participants: Two hundred nine eyes from 108 patients who had a scheduled in-person outpatient ophthalmology clinic visit at an academic medical center. Methods: Enrolled patients were sent a .pdf document consisting of instructions and a printout ETDRS vision chart calibrated for 5 feet. Patients completed the VA test at home before the in-person appointment, where their VA was measured by an ophthalmic technician using a standard ETDRS chart. Survey questions about the ease of testing and barriers to completion were administered. For the bioequivalence test with a 5% nominal level, the 2 1-sided tests procedure was used, and an equivalent 90% confidence interval (CI) was constructed and compared with the prespecified 7-letter equivalence margin. Main Outcome Measures: The primary outcome was the mean adjusted letter score difference between the home and clinic tests. Secondary outcomes included the unadjusted letter difference, absolute letter difference, and survey question responses. Results: The mean adjusted VA letter score difference was 4.1 letters (90% CI, 3.2-4.9 letters), well within the 7-letter equivalence margin. Average unadjusted VA scores in clinic were 3.9 letters (90% CI, 3.1-4.7 letters) more than scores at home. The absolute difference was 5.2 letters (90% CI, 4.6-5.9 letters). Ninety-eight percent of patients agreed that the home test was easy to perform. Conclusions: An ETDRS VA test self-administered at home following a standardized protocol was equivalent to a standard technician-administered VA test in clinic in the examined population.