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Andrew M Williams,1 Wei Huang,2 Kelly W Muir,3,4 Sandra S Stinnett,3 Jordan S Stone,5 Jullia A Rosdahl3 1Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC, USA; 3Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA; 4Health Services Research and Development, Durham Veterans Affairs Medical Center, Durham, NC, USA; 5School of Medicine, University of California San Diego, La Jolla, CA, USA Purpose: To examine the factors associated with blindness from primary open-angle glaucoma (POAG) among black and white patients at our institution.Patients and methods: For this retrospective, case–control study, patients legally blind from POAG (“cases”) were matched on age, race, and gender with non-blind POAG patients (“controls”). Thirty-seven black case–control pairs and 19 white case–control pairs were included in this study. Clinical variables were compared at initial presentation and over the course of follow-up.Results: Black case–control pairs and white case–control pairs had similar characteristics at presentation, including cup-to-disc ratio and number of glaucoma medications. However, over the course of follow-up, black cases underwent significantly more glaucoma surgeries than matched controls (2.4 versus 1.2, p=0.001), whereas white cases and controls had no significant difference in glaucoma operations (0.9 versus 0.6, p=0.139). Our analysis found that glaucoma surgery is associated with blindness in black patients (odds ratio [OR] 1.6, 95% CI 1.1–2.2) but not in white patients (OR 1.5, 95% CI 0.7–3.2).Conclusion: Black and white case–control pairs with POAG shared similar risk factors for blindness at presentation. However, over the follow-up period, black cases required significantly more glaucoma surgeries compared to black controls, whereas there was no significant difference in surgery between white cases and controls. There was no difference in medication changes in either case–control set. Keywords: health disparities, glaucoma surgery, glaucoma treatment, glaucoma medications

Michelle J Kim, Sandra S Stinnett, Preeya K Gupta Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA Purpose: The goal of this study was to evaluate the effect of thermal pulsation treatment on tear film parameters, specifically osmolarity and matrix metalloproteinase-9 (MMP-9), in patients with meibomian gland dysfunction (MGD) and dry eye disease (DED).Methods: A single-center review of 189 eyes that underwent thermal pulsation treatment was performed. Data were collected on pre and posttreatment osmolarity, MMP-9, tear break-up time (TBUT), and ocular surface disease index (OSDI) score. Statistical analyses were performed to detect any significant differences after treatment.Results: Thermal pulsation treatment led to significant improvements in TBUT (mean increase from 4.5 to 8.5 seconds [P307 mOsm/L (ie, diagnostic for DED), there was a significant improvement in the mean tear osmolarity from 317.1 to 306.6 mOsms/L after treatment (P=0.002). Conclusion: Treating MGD is an important component of caring for the DED patient. Thermal pulsation treatment can improve MMP-9 levels on the ocular surface of patients with MGD and DED, as well as improve osmolarity in those with abnormal initial values. The present study suggests that meibomian glands play an important role in tear film dynamics and, as such, effective therapy such as thermal pulsation treatment aimed at improving meibomian gland health, can aid the restoration of normal tear film parameters and decrease patient symptoms of DED and MGD. Keywords: thermal pulsation, dry eye disease, meibomian gland dysfunction, osmolarity, matrix metalloproteinase-9

Isaiah J Davies,1 Ninita H Brown,2 Joanne C Wen,3 Sandra S Stinnett,1 Kelsey Kubelick,4,5 Roma P Patel,6 Kristin L Benokraitis,7 Latoya Greene,1 Curry Cheek,1 Kelly W Muir1,8 1Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; 2Metrolina Eye Associates, Charlotte, NC, USA; 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 5Wallace H Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia, USA; 6University of California Davis Health System Eye Center, Sacramento, CA, USA; 7EG-GILERO, Durham, NC, USA; 8Health Services Research & Development, Durham VA Medical Center, Durham, NC, USA Purpose: This study tested the feasibility of using an upright eyedrop bottle (UEB), a device designed to assist patients with eyedrop placement without reclining their head. Patients and methods: Experienced eyedrop users were enrolled who answered “yes” to the question, “Do you ever have trouble getting your eyedrops in?” After being shown a multimedia presentation and answering a questionnaire regarding eyedrop usage, participants were observed instilling eyedrops. Participants were instructed to instill a single eyedrop in each eye with both a standard bottle and the UEB. They repeated this process three times. With each trial, the amount of time taken to instill drops was recorded, as well as whether a drop landed in the eye (accuracy), if excess drops were used, and if the bottle tip was contaminated. Results: Forty participants were enrolled, with an average age of 72.4±8.9 years; the majority were females (24 females). Thirty-four participants had been using eyedrops for at least 1 year. The time required to instill eyedrops was significantly less with the UEB in the second and third trials. There was no difference in accuracy between the conventional bottle and the UEB in the left or right eye in any trials. Significantly more participants used excess number of drops while using the conventional bottle in both the left and right eyes in all three trials. The bottle tip was never contaminated with the UEB. Depending on the trial and the eye, the conventional bottle was contaminated by between 42% and 53% of participants. Conclusion: The UEB has the potential to assist patients with eyedrop placement. Although there was no difference in accuracy between the UEB and the conventional bottle, the UEB was associated with less use of excess drops and less contamination of the bottle tip, compared to the conventional bottle. Keywords: glaucoma, compliance, medical devices

Brian E Goldhagen,1 Karen Kingsolver,2 Sandra S Stinnett,1 Jullia A Rosdahl1 1Department of Ophthalmology, 2Department of Family and Community Medicine, Duke University Medical Center, Durham, NC, USABackground and objective: Stress and burnout impact resident physicians. This prospective study tests the hypothesis that a mindfulness-based resilience intervention would decrease stress and burnout in residents.Methods: Resident physicians from the Departments of Family Medicine, Psychiatry, and Anesthesia at Duke University, Durham, NC, USA, participated in two or three 1-hour sessions of mindfulness-based resilience activities, which introduced mindful-awareness and included practical exercises for nurturing resilience. Anonymous surveys were distributed before (completed by 47 residents) and after the intervention (both completed by 30 residents); a follow-up survey was distributed 1 month later (seven residents completed all three surveys). The survey included the Depression Anxiety Stress Scale, 21-question version (DASS-21), the Oldenburg Burnout Inventory, the Mindful Attention Awareness Scale, and ten questions from the Cognitive Failures Questionnaire.Results: At baseline, most residents’ scores were in the normal range with respect to stress; however, female residents had higher DASS-21 scores than male residents (31.7, females vs 18.4, males; P=0.002). Most residents’ burnout scores were in the abnormal range, both with respect to exhaustion (38/47 residents, subscore ≥2.25) and disengagement (37/47 residents, subscore ≥2.1). Higher perceived levels of stress correlated with the instruments. Analysis of the surveys before and after the intervention showed no significant short-term change in stress, burnout, mindful-awareness, or cognitive failure. There was a trend for females and post-medical school graduate year 1 and 2 (PGY1 and PGY2) residents to have a reduction in DASS-21 scores after intervention. There was also a trend of reduced stress and burnout in residents who perceived higher stress.Conclusion: Residents who are female, PGY1 and PGY2, and who perceive residency to be stressful may benefit most from a mindfulness-based resilience intervention. Keywords: physician, self-care, wellness, medical trainees

PURPOSE: In the current political and economic climate, there is a desire to reduce health care costs; diagnostic imaging expenditure is one area of particular interest. The authors present a meta-analysis of the relative frequency of imaging utilization in the setting of self-referral compared with that of non-self-referral and a simulation of increased cost to Medicare Part B on the basis of this relative frequency. METHODS: The MEDLINE database was searched systematically. Specific inclusion criteria for relative frequency calculations were a numerator (number of patients imaged) and denominator (number of total patients seen) in each group (self-referrers and radiologist referrers). The relative risk of self-referral was determined for each group and is defined by the 'relative frequency' of imaging utilization for the self-referrers divided by the frequency for the radiologist referrers. Relative frequency represents the increased (if >1) or decreased (if <1) chance of imaging by self-referrers over radiologist referrers. The meta-analysis was used to combine imaging frequencies for each referral condition of the individual studies that met inclusion criteria for an overall estimate of relative frequency, using a random-effects model to account for the variations among the studies. Relative frequency data were then used to perform a cost simulation to Medicare Part B using 2006 data. RESULTS: The initial search yielded 334 articles, 5 of which met the threshold for inclusion. In these 5 studies, 76,905,162 total episodes of care were analyzed. The individual relative frequency of imaging in the setting of self-referral ranged from 1.60 to 4.50. The combined relative frequency was 2.16 (95% confidence interval, 2.15-2.16) using the fixed-effects model and 2.48 (95% confidence interval, 1.90-3.24) using the random-effects model. For 2006 Government Accountability Office (GAO) data, the estimated cost of increased imaging in the setting of self-referral was $3.6 billion, but a range of costs was also provided to account for potential inaccuracies in the GAO data. CONCLUSIONS: The existing literature yields a combined relative frequency of imaging of 2.48 (95% confidence interval, 1.90-3.24) for self-referrers compared with non-self-referrers. Precise extrapolation of Medicare Part B costs attributable to self-referral would require changes in reporting requirements for imaging equipment ownership. Cost simulation results total billions of dollars annually and may be irrespective of potential inaccuracies in the GAO data as a result of Current Procedural Terminology((R)) coding ambiguity and nontransparent reporting of equipment ownership. [ABSTRACT FROM AUTHOR]

Continuous exposure to environmental hypoxia (11% O 2 ) has been shown to markedly slow the progressive degeneration of retinal ganglion cells (RGCs) in a mouse model of mitochondrial optic neuropathy with RGC-specific deletion of the key mitochondrial complex I accessory subunit ndufs4. As a first step toward identifying the therapeutic mechanism of hypoxia in this model, we conducted a series of experiments to investigate the role of the hypoxia-inducible factor (HIF) regulatory pathway in RGC neuroprotection. Vglut2-Cre; ndufs4 loxP/loxP mice were crossed with strains bearing floxed alleles of the negative HIF regulatory vhl or of the two major HIF α-subunit isoforms, Hif1α and Hif2α. Deletion of vhl within ndufs4-deficient RGCs failed to prevent RGC degeneration under normoxia, indicating that HIF activation is not sufficient to achieve RGC rescue. Furthermore, the rescue of ndufs4-deficient RGCs by hypoxia remained robust despite genetic inactivation of Hif1α and Hif2α. Our findings demonstrate that the HIF pathway is entirely dispensable to the rescue of RGCs by hypoxia. Future efforts to uncover key HIF-independent molecular pathways induced by hypoxia in this mouse model may be of therapeutic relevance to mitochondrial optic neuropathies such as Leber hereditary optic neuropathy., (© 2024. The Author(s).)

Purpose: To describe the frequency, findings, and interventions of patients' emergency department (ED) visits after all types of glaucoma surgery DESIGN: Retrospective cohort study SUBJECTS: All surgical patients with glaucoma between 2013 and 2021 METHODS: This single institution study collected demographics, surgery type, and surgical parameters for each patient. Subsequently, for those visiting the ED within 50 days of surgery, data were collected on reason for visit, findings, and ophthalmic intervention. Logistic regression models were used to determine the odds of ED visits based on multiple risk factors., Main Outcome Measures: Postoperative presentation to ED RESULTS: Among 9155 surgeries in 5505 patients, 5.7% had ED visits within 50 days, with 46.3% having ocular complaints. Patients with ocular diagnoses presented earlier than those without (P < 0.001). Patients who presented to the ED with an ocular diagnosis were found to be significantly younger than those who did not present (62.2 ± 18.6 vs. 65.4 ± 18.0 years old, P < 0.028). Furthermore, white patients were more likely than Black patients to present with an ocular diagnosis compared to a nonocular diagnosis (odds ratio [OR]: 2.64; 95% confidence interval [CI], 1.67-4.18; P < 0.001). Patients undergoing their first glaucoma surgery had a much higher chance of presenting to the ED compared to patients who had undergone more than one surgery (OR: 3.75; 95% CI, 2.74-5.14; P < 0.001). Those who underwent traditional surgeries were more likely than patients with trabecular meshwork bypass stent to present to the ED with an ocular diagnosis (OR: 3.02; 95% CI, 1.29-7.08; P = 0.011). Filtering surgeries and glaucoma drainage device (GDD) revisions exhibited more vision-threatening conditions than GDDs (P = 0.037 and P = 0.010 respectively). Ophthalmology consultation was sought for 88.0% of ocular diagnoses. Most received medical therapy (71.0%), primarily intraocular pressure-lowering drops., Conclusion: Emergency department visits after glaucoma surgery are infrequent, yet more often seen in younger patients or those undergoing their first glaucoma surgery. Trabecular meshwork bypass stent, but not trabecular meshwork excision and/or Schlemm canal dilation, were less likely to present to the ED than traditional surgeries. Filtering surgeries and tube revisions presented more often with visual threatening conditions., Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Analyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP)., Design: Retrospective multicenter study., Participants: Patients with OMMP seen at the Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990 to 2022., Methods: Data at presentation on demographics, direct immunofluorescence, ocular findings, sites of extraocular manifestations (EOMs), and previous treatments in patients with a clinical or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes., Main Outcome Measures: (1) Inflammatory control (no conjunctival inflammation in both eyes at 3 months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥ 1 cicatrizing stage progression in either eye); and (4) vision loss (≥ 2 Snellen lines)., Results: A total of 117 patients (234 eyes), 61% (71/117) of whom were women, with a mean age of 66.6 (SD: 12.4) years (range: 37-97 years) and median follow-up of 34 months (interquartile range: 16-66 months; range: 3-265 months), were enrolled. Inflammatory control was achieved in 57% of patients (67/117), with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital involvement (adjusted odds ratio [aOR]: 12.51; 95% confidence interval [CI]: 2.61-59.99; P = 0.002) and corneal scarring (aOR: 3.06; 95% CI, 1.15-8.14; P = 0.025), as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% of patients (23/117), 12% of patients (14/117), and 27% of patients (32/117), respectively. Baseline corneal scarring was a risk factor for relapse (adjusted hazard ratio: 4.14; 95% CI: 1.61-10.62; P = 0.003), progression (aOR: 11.46; 95% CI: 1.78-73.75; P = 0.010), and vision loss (aOR: 3.51; 95% CI: 1.35-9.10; P = 0.010). HR-EOM was associated with stage progression (aOR, 34.57; 95% CI, 6.57-181.89; P<0.001) and vision loss (aOR, 8.42; 95% CI, 2.50-28.42; P = 0.001). No significant differences were found between IMT regimes and relapse (P = 0.169)., Conclusions: Ocular mucous membrane pemphigoid presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate and compare subbasal corneal nerve parameters of the inferior whorl in patients with dry eye disease (DED), neuropathic corneal pain (NCP), and controls using a novel deep-learning-based algorithm to analyze in-vivo confocal microscopy (IVCM) images., Methods: Subbasal nerve plexus (SNP) images of the inferior whorl of patients with DED (n = 49, 77 eyes), NCP (n = 14, 24 eyes), and controls (n = 41, 59 eyes) were taken with IVCM and further analyzed using an open-source artificial intelligence (AI)-based algorithm previously developed by our group. This algorithm automatically segments nerves, immune cells, and neuromas in the SNP. The following parameters were compared between groups: nerve area density, average nerve thickness, average nerve segment tortuosity, junction point density, neuroma density, and immune cell density., Results: 160 eyes of 104 patients (63 % females), aged 56.8 ± 15.4 years, were included. The mean nerve area density was significantly lower in the DED (P = 0.012) and NCP (P < 0.001) groups compared to the control group. The junction point density was lower in the NCP group compared with control (P = 0.001) and DED (P = 0.004) groups. The immune cell density was higher in the DED group compared with controls (P < 0.001)., Conclusions: Deep-learning-based analysis of IVCM images of the corneal SNP inferior whorl distinguished a decreased mean nerve area density in patients with DED and NCP compared with controls and an increased immune cell density in patients with oGVHD- and SS-associated DED. These findings suggest that the inferior whorl could be used as landmark to distinguish between patients with DED and NCP., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Point scanning retinal imaging modalities, including confocal scanning light ophthalmoscopy (cSLO) and optical coherence tomography, suffer from fixational motion artifacts. Fixation targets, though effective at reducing eye motion, are infeasible in some applications (e.g., handheld devices) due to their bulk and complexity. Here, we report on a cSLO device that scans the retina in a spiral pattern under pseudo-visible illumination, thus collecting image data while simultaneously projecting, into the subject's vision, the image of a bullseye, which acts as a virtual fixation target. An imaging study of 14 young adult volunteers was conducted to compare the fixational performance of this technique to that of raster scanning, with and without a discrete inline fixation target. Image registration was used to quantify subject eye motion; a strip-wise registration method was used for raster scans, and a novel, to the best of our knowledge, ring-based method was used for spiral scans. Results indicate a statistically significant reduction in eye motion by the use of spiral scanning as compared to raster scanning without a fixation target.

Purpose: To assess the severity, progression, and treatment burden of diabetic retinopathy (DR) in patients after bariatric surgery compared with controls. Methods: A retrospective cohort study was performed of patients with type 2 diabetes and DR seen at the Duke Eye Center between 2014 and 2023. Clinical data included hemoglobin A 1c (HbA 1c ), diagnostic stage of DR, diabetic macular edema (DME) or vitreous hemorrhage (VH), visual acuity (VA), and treatment burden at baseline and follow-up. Generalized estimating equation analysis was used to account for the correlation between 2 eyes of the same patient. Results: Sixteen patients who had bariatric surgery were matched by age, sex, and duration of diabetes with 60 control patients managed medically during the same time period. The HbA 1c level, severity of DR, presence of DME or VH, VA, and treatment burden were not significantly different (all P  > .05) at the baseline examination. On average, patients were followed for 6 years. The HbA 1c level at the follow-up was significantly lower in the bariatric surgery group (6.4% vs 8.5%; P  < .001). At the follow-up, the treatment burden was reduced in the bariatric surgery group compared with the control group ( P  = .04). There was a clear trend toward reduced progression of DR and treatment burden in the bariatric surgery group over the follow-up. Conclusions: Bariatric surgery may improve glycemic control, stabilize DR progression, and reduce the treatment burden, which may have a significant impact on quality of life for patients with DR., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: This study aimed to identify peripapillary microvascular changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI)., Patients and Methods: In this prospective study, 66 eyes of 36 subjects with AD, 119 eyes of 63 with MCI, and 513 eyes of 265 controls with normal cognition were enrolled. Peripapillary capillary perfusion density (CPD), capillary flux index (CFI), and retinal nerve fiber layer (RNFL) thickness were determined., Results: Average CPD differed significantly between all three groups ( P = 0.001), being significantly greater in AD vs controls (0.446 ± 0.015 vs 0.439 ± 0.017, P = 0.001) and MCI vs controls (0.443 ± 0.020 vs 0.439 ± 0.017, P = 0.007) but not AD vs MCI ( P = 0.69). CFI and average RNFL thickness did not significantly differ among groups (all P > 0.05)., Conclusion: Peripapillary CPD is increased in eyes with AD or MCI compared to controls despite similar RNFL thickness. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:78-84.] .

Objective: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD)., Methods: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation., Results: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups., Conclusions: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Joseph et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To evaluate the retinal and choroidal microvasculature and structure in individuals with dementia with Lewy bodies (DLB) compared with controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: An institutional review board-approved cross-sectional comparison of patients with DLB and cognitively normal controls was performed. The Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec) was used to obtain OCT and OCTA images. Results: Thirty-four eyes of 18 patients with DLB and 85 eyes of 48 cognitively normal patients were analyzed. The average capillary perfusion density (CPD) was higher in the DLB group than in the control group ( P  = .005). The average capillary flux index (CFI) and ganglion cell inner-plexiform layer (GC-IPL) thickness were lower in the DLB group than in the control group ( P  = .016 and P  = .040, respectively). Conclusions: Patients with DLB had an increased peripapillary CPD, decreased peripapillary CFI, and attenuated GC-IPL thickness compared with those with normal cognition., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Purpose: To compare the risk factors and clinical outcomes in patients younger than 50 years with acute, treatment-naïve branch retinal vein occlusion (BRVO) with outcomes in patients 50 years or older. Methods: Patients diagnosed with acute, treatment-naïve BRVO at Duke Eye Center over a 9.5-year period who had BRVO with onset 3 months or less before presentation, BRVO with macular involvement, and 12 months or more of follow-up were included. Demographic data, presenting clinical features, risk factors, treatment patterns, and clinical outcomes were extracted during a retrospective review of medical records. Results: Of 302 patients identified, 23 were younger than 50 years (younger group) and 279 were 50 years or older (older group). Compared with older patients, younger patients had similar rates of hypertension ( P  = .275), diabetes mellitus ( P  = 1.000), smokers ( P  = .787), and open-angle glaucoma ( P  = .628). The younger group had a lower rate of hyperlipidemia than the older group (35% vs 59%) ( P  = .028). The 2 groups had similar presenting logMAR visual acuities (VAs) in the BRVO eye ( P  = .131). At the final follow-up, younger patients had significantly better logMAR VA in the BRVO-affected eye than older patients (mean 0.51 ± 0.65 vs 1.01 ± 1.20) ( P  = .016). The 2 groups had similar treatment burdens at 1 year ( P  = .516) and at the final follow-up ( P  = .782). Conclusions: Younger patients with acute, treatment-naïve BRVO have similar risk factors and treatment patterns as older patients, except for a lower rate of hyperlipidemia. Younger patients with BRVO may have similar presenting VA as older BRVO patients but better final VA, suggesting that age may be a potential prognostic factor., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Thomas is a consultant to Alimera, Allergan, Avesis, Eyepoint, and Genentech, and Novartis. Dr. Fekrat received patent royalties from Alcon and research support from Genentech and Optos and is a consultant to Glaukos and Bausch + Lomb. None of the other authors reported financial disclosures or conflicts., (© The Author(s) 2023.)

Purpose: The volume of microinvasive glaucoma surgery (MIGS) has increased dramatically in recent years, from 31 059 in 2013 to 69 420 in 2018. We investigated the impact of this trend on trainees by determining the proportion of glaucoma surgeries performed by fellows-in-training comprised by MIGS, trabeculectomies, and aqueous shunts., Design: Retrospective analysis., Participants: Fellows-in-training at Glaucoma Fellowship Programs certified by the Association of University Professors of Ophthalmology Fellowship Compliance Committee (AUPO-FCC) METHODS: We analyzed aggregate summaries of surgeries performed by fellows as reported to the AUPO-FCC from the academic years (AYs) beginning in 2014 through AY 2020. Each report lists the average number of procedures performed per surgery type per fellow. We combined these averages to create a sum "average number surgeries performed" across glaucoma surgeries and computed the proportion that each surgery type (MIGS, trabeculectomies, and aqueous shunts) represented within the total average number of surgeries performed per year., Main Outcome Measures: Average number of procedures performed for each surgery type as well as the proportion that each surgery type (MIGS, trabeculectomies, and aqueous shunts) represented within the total average number of procedures performed per year., Results: Average number of MIGS performed is significantly greater in later years compared with earlier years (P < 0.001). The average number of trabeculectomies performed between AYs 2014 and AY 2020 ranged from 21.8 to 31.9 and decreased, on average, by - 0.80 year-to-year. The average number of aqueous shunts performed between AY 2014 and AY 2020 ranged from 44.7 to 49.5, with an average increase of + 0.8 year-to-year. The total average number of procedures performed (across all 3 surgical subtypes) increased on average by + 4.8 procedures each year., Conclusions: Since 2014, fellows are performing increasing numbers of MIGS procedures, whereas the total number of trabeculectomies and aqueous shunt surgeries performed each year remain similar, resulting in a net increase in total number of procedures performed per fellow each year. This suggests the increase in MIGS is not associated with a substantial decline in trabeculectomies or aqueous shunts performed by glaucoma fellows., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To validate GATHER-1 inclusion criteria and the study's primary anatomic end point by assessing the reproducibility of geographic atrophy (GA) measurements and factors that affect reproducibility., Design: Post hoc analysis of phase II/III clinical trial., Subjects: All 286 participants included in the GATHER-1 study., Methods: For each subject, blue-light fundus autofluorescence (FAF), color fundus photographs, fluorescein angiograms, and OCT scans were obtained on the study eye and fellow eye. Geographic atrophy area and other lesion characteristics were independently graded by 2 experienced primary readers. If the 2 readers differed on gradeability, GA area (> 10%) or other lesion characteristics, the image was graded by an arbitrator whose measurement or characterization was the final grade., Main Outcome Measures: The main outcome measures were gradeability and reproducibility of FAF imaging data. Imaging data included lesion area, confluence of GA with peripapillary atrophy (PPA), whether GA involved the foveal centerpoint, and type of hyperautofluorescence pattern., Results: A total of 2004 images (1002 visits, 286 participants) were analyzed. Gradeability (90.5%) and interreader gradeability concordance (90.2%) were high across all visits. Study eye images were more gradable compared with fellow-eye images. A greater proportion of smaller lesions required arbitration, but interreader reproducibility was consistently high for all images. There was no difference in gradeability, gradeability concordance, or lesion-area concordance for images with PPA-confluent GA compared with those with nonconfluent PPA. Foveal centerpoint-involving lesions had lower gradeability and lesion-area concordance. Images with diffuse patterns of hyperautofluorescence had better gradeability and gradeability concordance than those with nondiffuse patterns but had no difference in lesion-area or lesion-area concordance., Conclusions: There is high gradeability and excellent reproducibility measures across all images. These data support the validity of conclusions from GATHER-1 and the chosen inclusion criteria and end point., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Introduction: Cystoid macular edema (CME) is the most common cause of central vision loss in eyes with branch retinal vein occlusion (BRVO eyes). In recent literature, choroidal vascularity index (CVI) has been proposed to be an enhanced depth imaging optical coherence tomography (EDI-OCT) metric that may help characterize choroidal vascular changes in the setting of retinal ischemia, and potentially prognose visual outcomes and treatment patterns for patients with BRVO-related CME. This study sought to further characterize choroidal vascular changes in BRVO by comparing the CVI, subfoveal choroidal thickness (SFCT), and central subfield thickness (CST) in BRVO eyes with CME compared to unaffected fellow eyes., Methods: This was a retrospective cohort study. Subjects included treatment-naïve BRVO eyes with CME diagnosed within 3 months of onset of symptoms and unaffected fellow eyes. EDI-OCT images were collected at baseline and at the 12-month follow-up visit. CVI, SFCT, and CST were measured. Demographics, treatment patterns, and best-corrected visual acuity (VA) were abstracted. Median CVI, SFCT, CST, and VA were compared between the two cohorts. Longitudinal relationships between these variables were analyzed., Results: A total of 52 treatment-naïve eyes with BRVO and CME and 48 unaffected fellow eyes were identified. Baseline CVI was lower in eyes with BRVO than in fellow eyes (64.7% vs. 66.4%, P = 0.003). At 12 months, there was no difference in CVI between BRVO eyes and fellow eyes (65.7% vs 65.8%, P = 0.536). In BRVO eyes, there was a strong correlation between reduced CST and improved VA over the 12-month study period (r = 0.671, P < 0.001)., Conclusion: There are differences in CVI in treatment-naïve BRVO eyes with CME at presentation compared to fellow eyes, but these differences resolve over time. Anatomic changes in macular thickness in BRVO eyes with CME may be correlated with VA outcomes., (© 2023. The Author(s).)

Objective: The current study assessed pregnant individuals' intention to accept routine and COVID-19 vaccines for their baby after birth, and to identify key demographic (e.g., age) and nondemographic characteristics (e.g., prior birth) associated with vaccination intention., Methods: The authors conducted a cross-sectional survey with pregnant individuals attending prenatal practices affiliated with a large academic medical center and two rural county health departments in the southeastern United States. The survey included 11 questions and was self-administered by pregnant individuals in clinic settings. The final analysis included responses from 443 pregnant individuals., Results: Only 67% of pregnant individuals planned to vaccinate their baby with all recommended routine vaccines; an additional 22% reported having questions about recommendations. Only 35% of pregnant individuals said they would vaccinate their baby as soon as possible with a COVID-19 vaccine. Younger pregnant individuals and those identifying as Black or African American had lower routine and COVID-19 vaccination intention. Routine vaccination, but not COVID-19 vaccination intention, was associated with familiarity with routine vaccination schedule, trimester of pregnancy, Hispanic ethnicity, history of prior birth, and having access to a computer., Conclusion: Study findings support differential tailoring of future interventions targeting pregnant individuals to promote routine and COVID-19 vaccines for children., (© 2022 International Federation of Gynecology and Obstetrics.)

This retrospective study of 68 premature infants examined whether there was a difference between male and female mixed-sex multiple gestation infants with regard to stage of retinopathy of prematurity (ROP) developed or need for ROP treatment. We found that among mixed-sex twin infants there was no statistically significant difference between sexes in most severe ROP stage developed or need for ROP treatment, but males were treated at an earlier postmenstrual age (PMA) than females, despite females having a lower mean birthweight and slower mean growth velocity compared to males., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Despite the increased emphasis on evidence-based medicine, the current state of evidence behind ophthalmology clinical practice guidelines is unknown. The purpose of this systematic analysis was to understand the levels of evidence (LOE) supporting American Academy of Ophthalmology (AAO) Preferred Practice Pattern (PPP) guidelines, assess changes over time, and compare LOE across ophthalmology subspecialties., Methods: All current PPP guidelines and their immediate predecessors were comprehensively reviewed to identify all recommendations with LOE provided (I [randomized controlled trials], II [case-control or cohort studies], and III [nonanalytic studies])., Results: Twenty-three out of 24 current PPPs had a prior edition. Among the PPPs with a prior edition, the number of recommendations with LOE decreased from 1254 in prior PPPs to 94 in current PPPs. The number of recommendations with LOE I decreased from 114 to 83, LOE II decreased from 147 to 2, and LOE III decreased from 993 to 9. However, the proportion of LOE I recommendations increased from 9 to 88%, driven by a disproportionate decrease in reporting of evidence lower than LOE I. Subgroup analysis by subspecialty showed similar trends (LOE I recommendations in prior PPPs vs current PPPs: retina: 57 [12%] vs 19 [100%]; cornea: 33 [5%] vs 24 [100%]; glaucoma: 9 [23%] vs 17 [100%]; cataract: 13 [17%] vs 18 [100%])., Conclusions: Trends in LOE reporting in PPP guidelines indicate an increasing emphasis on evidence from randomized controlled trials from 2012 to 2021. The decline in the number of recommendations with LOE reported suggests an area for improvement in future guidelines as the presence of LOE is crucial to facilitate interpretation of clinical practice guidelines., (© 2023. The Author(s).)

Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), and normal cognition (NC)., Design: Cross sectional study., Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis., Methods Intervention or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay., Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging., Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49-0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67-0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease., Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability., Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article., (© 2023 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Purpose: To test whether continuous hypoxia is neuroprotective to retinal ganglion cells (RGCs) in a mouse model of mitochondrial optic neuropathy., Methods: RGC degeneration was assessed in genetically modified mice in which the floxed gene for the complex I subunit NDUFS4 is deleted from RGCs using Vlgut2-driven Cre recombinase. Beginning at postnatal day 25 (P25), Vglut2-Cre;ndufs4loxP/loxP mice and control littermates were housed under hypoxia (11% oxygen) or kept under normoxia (21% oxygen). Survival of RGC somas and axons was assessed at P60 and P90 via histological analysis of retinal flatmounts and optic nerve cross-sections, respectively. Retinal tissue was also assessed for gliosis and neuroinflammation using western blot and immunofluorescence., Results: Consistent with our previous characterization of this model, at least one-third of RGCs had degenerated by P60 in Vglut2-Cre;ndufs4loxP/loxP mice remaining under normoxia. However, continuous hypoxia resulted in complete rescue of RGC somas and axons at this time point, with normal axonal myelination observed on electron microscopy. Though only partial, hypoxia-mediated rescue of complex I-deficient RGC somas and axons remained significant at P90. Hypoxia prevented reactive gliosis at P60, but the retinal accumulation of Iba1+ mononuclear phagocytic cells was not substantially reduced., Conclusions: Continuous hypoxia achieved dramatic rescue of early RGC degeneration in mice with severe mitochondrial dysfunction. Although complete rescue was not durable to P90, our observations suggest that investigating the mechanisms underlying hypoxia-mediated neuroprotection of RGCs may identify useful therapeutic strategies for optic neuropathies resulting from less profound mitochondrial impairment, such as Leber hereditary optic neuropathy.

Purpose: To evaluate indications and postoperative outcomes of inferonasal Ahmed and Baerveldt glaucoma drainage devices (GDDs) in pediatric glaucoma., Methods: This retrospective study included patients ≤18 years of age at inferonasal GDD placement, from June 2013 to September 2021. Demographic information, indications, and outcomes were recorded. Successful eyes had intraocular pressure (IOP) ≥5 and ≤21 mm Hg or (in severe cases, where entry IOP was ≤21 mm Hg) 20% below preoperative values without additional IOP-lowering surgery or vision-threatening complications., Results: A total of 68 eyes of 52 patients were included. Mean age was 9.8 ± 5.8 years. Most common diagnoses included primary congenital glaucoma (n = 28 eyes [41%]) and glaucoma following cataract surgery (n = 12 eyes [18%]). Success rates by Kaplan-Meier survival analysis (95% CI) at 1, 2, 3, and 5 years were 62.2% (49.4-72.7), 49.0% (36.3-60.6), 36.8% (24.0-49.8), and 31.9% (18.5-44.5), respectively. Surgical failure was associated with Ahmed (vs Baerveldt) GDD (HR = 3.2; P = 0.002) and inferonasal site as initial (vs subsequent) GDD received (HR = 2.2; P = 0.048). Twenty-five eyes (36.7%) had at least one complication. Although vision-threatening complications were uncommon (n = 2 eyes [3%]), less severe complications were relatively common and included new/worsened strabismus (n = 9 patients [17%]), corneal edema (n = 6 eyes [9%]), lens opacities (n = 4 [6%]), tube or patch graft exposure (n = 3 [4%]), tube blockage (n = 2 eyes [3%]), and other (n = 8 eyes [12%])., Conclusions: In this study cohort, inferonasal GDDs for childhood glaucoma had modest success, with frequent though rarely vision-threatening complications., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To assess retinal microvascular alterations in individuals with amnestic mild cognitive impairment (MCI) and nonamnestic MCI., Methods: One hundred twelve eyes of 59 amnestic MCI participants, 32 eyes of 17 nonamnestic MCI participants, and 111 eyes of 56 controls with normal cognition were included. Optical coherence tomography angiography vessel density and perfusion density in the Early Treatment Diabetic Retinopathy Study 3-mm circle and ring were assessed. Retinal thickness parameters including retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness were also analyzed. Multivariable generalized estimating equations were used for statistical analysis., Results: Perfusion density in the 3-mm inner ring was significantly lower in amnestic MCI patients when compared with nonamnestic MCI participants (0.29 ± 0.03 vs. 0.34 ± 0.09, P = 0.025) and controls with normal cognition (0.29 ± 0.03 vs. 0.39 ± 0.02, P < 0.001), after adjustment for age and sex as covariates. Vessel density, retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness did not differ among or between diagnostic groups., Conclusion: Perfusion density was significantly reduced in individuals with amnestic MCI, compared with those with nonamnestic MCI and controls with normal cognition.

Purpose: To assess the baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between apolipoprotein ε4 (APOE ε4) carriers and noncarriers with normal cognition., Design: Prospective study., Subjects: Four hundred thirteen eyes of 218 individuals with normal cognition aged ≥ 55 years with known APOE status (98 APOE ε4 carriers and 120 noncarriers). The exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease., Methods: OCT and OCT angiography (OCTA) were performed at baseline and 2 years (Zeiss Cirrus HD-OCT 5000 with AngioPlex; Zeiss Meditec). The groups were compared using sex- and age-adjusted generalized estimating equations., Main Outcome Measures: OCT parameters: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), and choroidal vascularity index. OCT angiography parameters: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary PD (CPD), and capillary flux index (CFI). The rate of change per year was calculated., Results: At the baseline, the APOE ε4 carriers had lower CST (P = 0.018), PD in the 6-mm ETDRS circle (P = 0.049), and temporal CFI (P = 0.047). Seventy-one APOE ε4 carriers and 78 noncarriers returned at 2 years; at follow-up, the 6-mm ETDRS circle (P = 0.05) and outer ring (P = 0.049) showed lower PD in the APOE ε4 carriers, with no differences in the rates of change between the groups (all P > 0.05)., Conclusions: There was exploratory evidence of differences in the CST, PD, and peripapillary CFI between the APOE ε4 carriers and noncarriers with normal cognition. Larger and longer-term studies may help further elucidate the potential prognostic value of these findings., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate visual function (VF) changes in early and intermediate age-related macular degeneration (eAMD and iAMD) over 24 months., Design: Prospective, observational natural history study., Participants: Participants were enrolled at the Duke Eye Center., Methods: A total of 101 subjects (33 with eAMD, 47 with iAMD, and 21 normal controls) were recruited. Visual function (VF) tests included best-corrected visual acuity (BCVA), low- luminance visual acuity (LLVA), microperimetry (MP), cone contrast tests (CCTs), and dark adaptation (DA). Mixed-effect model repeated measures based on absolute values and change from baseline identified VF tests differentiating AMD from controls and revealing longitudinal VF decline when controlling for covariates (baseline value, age, coronary artery disease, dry eye, and phakic status). Nine AMD genetic risk variants, combinations of these (genetic burden score), reticular pseudodrusen (RPD), and hyperreflective foci (HRF) were tested as predictors of diagnosis and VF performance., Main Outcome Measures: Longitudinal changes in VF metrics over 24 months., Results: A total of 70 subjects completed the 2-year visit (22 with eAMD, 31 with iAMD, and 17 controls). Percent reduced threshold (PRT) on MP and CCT red significantly distinguished iAMD versus controls after 12 and 24 months, respectively. Cone contrast test red, PRT, and absolute threshold (AT) on MP showed significant longitudinal deterioration of VF in iAMD versus baseline at 12 months and onward, however, with a reduced rate of worsening. The DA data confirmed a preexisting functional deficit in iAMD at baseline and revealed an increasing proportion of poorly performing iAMD subjects in DA over the study period. None of the other VF measures showed consistent significant changes among the normal, early, and intermediate groups or over time. The genetic burden score was significantly associated with AMD diagnosis (relative risk for iAMD = 1.64, P  < 0.01) and DA ( r  = 0.42, P  = 0.00005). Reticular pseudodrusen and HRF showed moderate associations with DA and weak to moderate associations with MP variables., Conclusions: In iAMD, MP variables, CCT red, and DA revealed slow and nonlinear functional decline over 24 months. A structure-function relationship in eAMD and iAMD stages was demonstrated among HRF, RPD, and DA, possibly modified by genetic risk factors. These structural and functional features represent potential end points for clinical trials in iAMD., (© 2022 by the American Academy of Ophthalmology.)

Dysregulated levels of growth/differentiation factor-15 (GDF15), a divergent member of the transforming growth factor-beta super family, have been found to be associated with the pathology of various diseases. In this study, we evaluated the levels of GDF15 in aqueous humor (AH) and serum samples derived from primary open-angle glaucoma (POAG) and age- and gender-matched non-glaucoma (cataract) patients to assess the plausible association between GDF15 and POAG. GDF15 levels were determined using an enzyme-linked immunosorbent assay, and data analysis was performed using the Wilcoxon rank sum test, or the Kruskal-Wallis test and linear regression. GDF15 levels in the AH ( n = 105) of POAG patients were significantly elevated (by 7.4-fold) compared to cataract patients ( n = 117). Serum samples obtained from a subgroup of POAG patients ( n = 41) also showed a significant increase in GDF15 levels (by 50%) compared to cataract patients. GDF15 levels were elevated in male, female, African American, and Caucasian POAG patients. This study reveals a significant and marked elevation of GDF15 levels in the AH of POAG patients compared to non-glaucoma cataract control patients. Although serum GDF15 levels were also elevated in POAG patients, the magnitude of difference was much smaller relative to that found in the AH.

Purpose: Our purpose was to review the preliminary outcomes of patients with uveal melanoma treated with iodine-125 plaques using a novel treatment planning approach ., Methods and Materials: This was a single institution, retrospective review of patients treated with iodine-125 brachytherapy for uveal melanoma from November 2016 to February 2019. We used 3-dimensional treatment planning with the Eye Physics Plaque Simulator to ensure that a minimum of 63 Gy covered a 2-mm circumferential tumor margin and the apex height of the tumor over 94 hours. Primary endpoints were local failure, systemic metastasis, final visual acuity (VA), and radiation retinopathy. Associations between primary endpoints and tumor characteristics/radiation dose were performed using univariate analysis., Results: Sixty-nine patients were included in the analysis. Mean largest basal diameter was 11.67 mm (range, 6-18; median, 12), and the average tumor thickness to the inner sclera was 3.18 mm (range, 0.5-9.3; median, 2.8). Molecular testing that was successfully performed in 59 patients revealed that 27% (16 of 59) had class 2 gene expression profile designation. Average follow-up posttreatment was 28.3 months (range, 4-46; median, 29), with 6% (4 of 69) developing local failure and 6% (4 of 69) developing metastasis over this duration. Average final VA (0.57 logMAR [Snellen 20/74]; range, 0-2.9; median, 0.3) was decreased from baseline (0.34 logMAR [Snellen 20/44]; range, 0-2.3; median, 0.1), and 48% (33 of 69) developed radiation retinopathy. Fifty percent of patients had a final VA 20/40 or better and 22% had a final VA 20/200 or worse., Conclusions: In patients with uveal melanoma, preliminary results with brachytherapy using Eye Physics plaques with a treatment plan that delivers 63 Gy to a 2-mm circumferential tumor margin and the tumor apex suggest effective disease control and favorable VA outcomes., (© 2022 The Authors.)

Purpose: To assess the repeatability of peripapillary OCT angiography (OCTA) in those with Alzheimer disease (AD), mild cognitive impairment (MCI), Parkinson disease (PD), or normal cognition., Design: Cross-sectional., Participants: Patients with a clinical diagnosis of AD, MCI, PD, or normal cognition were imaged. Those with glaucoma, diabetes mellitus, vitreoretinal pathology, and poor-quality images were excluded., Methods: Each eligible eye of each participant underwent 2 OCTA 4.5 × 4.5-mm peripapillary scans in a single session using a Zeiss Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec). The Zeiss software (v11.0.0.29946) quantified measures of perfusion in the radial peripapillary capillary (RPC) plexus in 4 sectors (superior, nasal, inferior, temporal). The average of these sectors was calculated and reported., Main Outcome Measures: Radial peripapillary capillary plexus perfusion was quantified using 2 parameters: capillary perfusion density (CPD) and capillary flux index (CFI). Intraclass correlation coefficients (ICCs) were used to quantify repeatability. For subjects who had both eyes included, the average values of each scan pair were used to assess interocular symmetry of CPD and CFI., Results: Of 374 eyes, 46 were from participants who had AD, 85 were from participants who had MCI, 87 were from participants who had PD, and 156 were from participants who had normal cognition. Capillary perfusion density ICC in AD = 0.88 (95% confidence interval [CI], 0.79-0.93), MCI = 0.95 (0.92-0.96), PD = 0.91 (0.87-0.94), and controls = 0.90 (0.87-0.93). Capillary flux index ICC in AD = 0.82 (0.70-0.90), MCI = 0.87 (0.80-0.91), PD = 0.91 (0.87-0.94) and controls = 0.85 (0.79-0.89). There were no significant differences in interocular variation in average CPD and CFI in AD, MCI, or PD (all P > 0.05). Isolated interocular sectoral CPD differences were noted in AD (nasal, P = 0.049; temporal, P = 0.024), PD (nasal, P = 0.036), and controls (nasal, P = 0.016). Interocular differences in CFI in the superior sector in MCI ( P = 0.028) and in average CFI for controls ( P = 0.035) were observed., Conclusions: Peripapillary OCTA repeatability in AD, MCI, and PD is good-excellent and similar to those with normal cognition. Insignificant interocular asymmetry in peripapillary OCTA suggests neurodegeneration may proceed uniformly; future studies may reveal the appropriateness of single-eye imaging., (© 2021 by the American Academy of Ophthalmology.)

Purpose: This proof-of-concept study evaluates the ability to assess eyelid measurements and the reproducibility of eyelid measurements using a simple measurement tool paired with digital cell phone photography in children., Methods: Seventy consecutive patients and their siblings, 2-19 years of age, were prospectively enrolled. Participants underwent clinical examination and cell phone photography with a simple measurement tool. An ophthalmologist and nonophthalmologist assessed photographs for interpalpebral fissure distance (IPFD), margin reflex distance-1 (MRD1), and levator function (LF). Clinical examinations and photographs were repeated on the same day in a random sample (n = 20). The agreement of grading photographs compared to clinical examination was assessed using Bland-Altman plots. Intra-grader repeatability of the clinical examination, repeatability of photographic technique, and interobserver reproducibility of photographic assessment was evaluated with intraclass correlation coefficients (ICC)., Results: Of photographs acquired, both graders considered quality good/fair in 100% to assess IPFD and MRD1, and 70% to assess LF. The mean difference (limits of agreement) in mm between clinical examination and photographic assessment was 1.1 (-1.5 to 3.8) for IPFD, 0.7 (-1.8 to 3.1) for MRD1, and 1.1 (-3.5 to 5.7) for LF. Intraobserver repeatability on clinical examination was excellent for IPFD (ICC = 0.81), MRD1 (ICC = 0.88), and LF (ICC = 0.94). Repeatability of photographic technique was fair for IPFD (ICC = 0.44) and good for MRD1 (ICC = 0.74) and LF (ICC = 0.77). Interobserver photographic assessment repeatability was excellent for IPFD (ICC = 0.94), MRD1 (ICC = 0.96), and LF (ICC = 0.92)., Conclusions: Photographic assessment of eyelid measurements in children is possible, highly reproducible between graders, and enables documentation for future comparison., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Guidelines on managing infants after initial anti-vascular endothelial growth factor (VEGF) treatment (eg, bevacizumab) for retinopathy of prematurity (ROP) are limited. We found that following initial bevacizumab treatment for ROP, prophylactically lasering infant eyes before hospital discharge reduced the number and duration of outpatient ROP screening examinations compared with following infants, per current United States (US) ROP screening guidelines., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To evaluate retinal microvascular changes in early and late-onset Alzheimer's disease (AD)., Patients and Methods: Eighty-six eyes of 50 late-onset AD participants, 27 eyes of 15 early onset AD participants, and 111 eyes of 57 cognitively normal controls were included. Optical coherence tomography angiography (OCTA) vessel density (VD) and perfusion density (PD) in Early Treatment Diabetic Retinopathy Study 3-mm and 6-mm circles and rings were assessed., Results: There was decreased PD in early onset AD 3-mm circle ( P = .026) and ring ( P = .026) versus controls as well as in late-onset AD 3-mm circle ( P = .023) and ring ( P = .023) versus controls. There was decreased VD in late-onset AD 3-mm circle ( P = .012) and ring ( P = .006). No parameters differed between early and late-onset AD ( P > .05)., Conclusions: AD eyes exhibited decreased retinal microvascular density compared to controls. Retinal parameters may not differ between early onset AD and late-onset AD after adjusting for age. [ Ophthalmic Surg Lasers Imaging Retina. 2021;52:336-344.] .

Purpose: In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset., Design: Retrospective study., Participants: Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants., Methods: We analyzed longitudinally captured SD OCT images and color photographs from 488 eyes of 488 participants with intermediate AMD at baseline. Sixty-two eyes with sufficient image quality demonstrated new-onset GA on color photographs during study years 2 through 7. The area of new-onset GA and one size-matched control region in the same eye were segmented separately, and corresponding spatial volumes on registered SD OCT images at the GA incident year and at 2, 3, and 4 years previously were defined. Differences in SD OCT features between paired precursor regions were evaluated through matched-pairs analyses., Main Outcome Measures: Localized SD OCT features 2 years before GA onset., Results: Compared with paired control regions, GA precursor regions at 2, 3, and 4 years before (n = 54, 33, and 25, respectively) showed greater drusen volume (P = 0.01, P = 0.003, and P = 0.003, respectively). At 2 and 3 years before GA onset, they were associated with the presence of hypertransmission (P < 0.001 and P = 0.03, respectively), hyperreflective foci (P < 0.001 and P = 0.045, respectively), OCT-reflective drusen substructures (P = 0.004 and P = 0.03, respectively), and loss or disruption of the photoreceptor zone, ellipsoid zone, and retinal pigment epithelium (RPE, P < 0.001 and P = 0.005-0.045, respectively). At 4 years before GA onset, precursor regions were associated with photoreceptor zone thinning (P = 0.007) and interdigitation zone loss (P = 0.045)., Conclusions: Evolution to GA is heralded by early local photoreceptor changes and drusen accumulation, detectable 4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable 1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: When the International Classification of Diseases 9th Revision (ICD-9) transitioned to the International Classification of Diseases 10th Revision (ICD-10), there was a marked increase in the complexity of International Classification of Diseases (ICD) codes with potential for improved specificity in clinical database research. The purpose of this study was to characterize the accuracy of coding for stage of diabetic retinopathy (DR) and DR-related complications (including vitreous hemorrhage, retinal detachment, and neovascular glaucoma) during this transition., Design: Retrospective chart review of 3 time periods corresponding to the use of ICD-9: 2014-2015; "early" use of ICD-10, 2015-2016; and "late" use of ICD-10, 2018-2019., Participants: Patients aged 18 years or older with a diagnosis of DR at a multispecialty academic institution., Methods: Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and kappa (κ) statistics were generated for each diagnosis. Generalized estimating equation (GEE) models were used to assess the significance of the variables., Main Outcome Measure: The main outcome was the proportion of agreement between the ICD code and the documented chart standard for stage of DR and DR-related complications., Results: A total of 600 patients were included in the study (average age, 61 years; range, 25-93 years). Overall, there was substantial agreement between the ICD codes for stage of DR and the documented standard (κ = 0.66). The proportion of ICD codes in agreement with the documented standard diagnosis increased with time: 66.5%, 78.5%, and 83.3% for ICD-9, "early" ICD-10, and "late" ICD-10, respectively. The odds of agreement were 2.67 (95% confidence interval [CI], 1.49-4.76, P < 0.001) and 3.96 (95% CI, 2.34-6.69, P < 0.0001) times greater for "early" and "late" ICD-10 codes compared with ICD-9 codes, respectively. For specific codes, the overall PPV, NPV, sensitivity, and specificity for nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were excellent (>90%). The odds of agreement were 19.70 (95% CI, 11.54-33.64, P < 0.0001) times greater for PDR than NPDR. Compared with the stage of DR, DR-related diagnoses were overall less accurately coded (κ = 0.61, 0.48, and 0.52 for vitreous hemorrhage, retinal detachment, and neovascular glaucoma, respectively)., Conclusions: Coding in ICD-10 is more accurate than in ICD-9, particularly for PDR compared with NPDR. The increased accuracy emphasizes the potential for ICD-10 coding to be used effectively in database research., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images., Methods: This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP: tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels: eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye)., Results: Of 832 examinations (99 infants), 745 images (89.5%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37 weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37 weeks for DI (P ≤ 0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32 weeks (P < 0.001)., Conclusions: Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: With the recent rise of teleophthalmology due to coronavirus disease, health care needs accurate and reliable methods of checking visual acuity remotely. The visual acuity as measured by the GoCheck Kids application was compared with that of the Amblyopia Treatment Study (ATS) and the authors' clinic protocol., Design: This was a prospective, comparison of visual acuity assessment methods., Methods: Established patients (3-18 years of age) in the practice of a single pediatric ophthalmologist were eligible. Visual acuity was measured 1) by GoCheck Kids mobile application, by the patient's family member; 2) by HOTV-ATS, by study personnel; and 3) by regular clinic protocol, by an ophthalmic technician. To assess agreement between measurement of acuity, intraclass correlations with 95% confidence intervals (CI) were computed., Results: A total of 53 children participated. The mean differences between GoCheck Kids and HOTV-ATS acuities (0.094) were significantly different (P < .001). The intraclass correlation coefficient (ICC) was 0.55 (95% CI: 0.40-0.68). The mean differences between GoCheck Kids and chart acuities (0.010) were not significantly different (P = .319; ICC: 0.59; 95% CI: 0.45-0.71). The mean differences between HOTV-ATS and chart acuities (0.084) were significantly different (P < .001; ICC: 0.66; 95% CI: 0.53-0.76). The percentages of eyes with visual acuity measured by GoCheck Kids within 1 line of the HOTV-ATS and chart acuity were 65.3% and 86.7%, respectively., Conclusions: GoCheck Kids as checked by a family member provided a modest correlation of visual acuity compared to the chart screen and a fair correlation of visual acuity compared to HOTV-Amblyopia Treatment Study protocol, although most were within 1 line., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Medical misinformation (MM) is a problem for both medical practitioners and patients in the 21 st century. Medical practitioners have anecdotally reported encounters with patient-held misinformation, but to date we lack evidence that quantifies this phenomenon. We surveyed licensed practitioners in the state of North Carolina to better understand how often patients mention MM in the clinical setting, and if medical practitioners are trained to engage with patients in these specific conversations. We administered an anonymous, online survey to physicians and physician assistants licensed to practice in the state of North Carolina. Questions focused on demographics, clinical encounters with MM, and training to discuss MM with patients. We received over 2800 responses and analyzed 2183 after removing ineligible responses. Our results showed that most respondents encountered MM from patients (94.2% (2047/2183)), with no significant differences between clinical specialty, time spent in practice, or community type. When asked about specific training, 18% (380/2081) reported formal experiences and 39% (807/289) reported informal experiences. MM has been salient due to the COVID-19 pandemic; however, it was present before and will remain after the pandemic. Given that MM is widespread but practitioners lack training on engaging patients in these conversations, a sustained effort to specifically train current and future practitioners on how to engage patients about MM would be an important step toward mitigating the spread of MM.

Purpose: To investigate long-term correlations between Matrix Metalloproteinase-9 (MMP-9) testing and dry eye (DE) parameters. Additionally, to evaluate variability in MMP-9 results over time and with anti-inflammatory treatment., Methods: Retrospective cohort study of DE patients with equal MMP-9 testing results (positive or negative) in both eyes and a minimum of 6 months of follow up. Our main outcome measure was to examine whether initial MMP-9 status affected change in DE parameters over time. Secondarily, we evaluated the frequency of MMP-9 status change over time and examined whether MMP-9 status change was impacted by treatment., Results: 67 patients (76% female) fit the inclusion criteria. Mean age was 63 years with a mean follow up of 10.6 months. The majority (37/67, 55%) had concomitant systemic immune disease. MMP-9 testing was positive in both eyes in 39 individuals (58%) and negative in both eyes in 27 (42%) individuals. Of all DE parameters, initial MMP status predicted change in tear production. Individuals in the MMP-9 positive group had a greater decrease in production from baseline to final visit compared to the negative group (-2.6 vs 2.1, P = 0.013). In those initially MMP-9 positive, the frequency of becoming MMP-9 negative was higher in eyes treated with anti-inflammatory therapy compared to artificial tears (22.9% vs 3.3%, P = 0.106). However, only Lifitegrast 5% showed statistical significance compared to artificial tears (31.3% vs 3.3%, P = 0.044)., Conclusions: Eyes with detectable MMP-9 had significantly decreased tear production over time compared to those without detectable MMP-9. Anti-inflammatory treatment more frequently normalized MMP-9 compared to PFATs., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To determine if meibomian gland architecture in a pediatric population is impacted by body mass index (BMI)., Methods: Prospective evaluation of 175 eyes of 175 pediatric patients from two clinics. Demographic and clinical information were reviewed. Symptoms of dry eye were assessed with the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Meibography was performed and grading of images was performed by a masked rater using a previously validated 5-point meiboscale (0-4) for gland atrophy and a 3-point score (0-2) for gland tortuosity., Results: 175 eyes of 175 participants aged 4-17 years (11.6 ± 3.7 years) were imaged. The mean meiboscore was 0.82 ± 0.94 (range 0-4) and the mean gland tortuosity score was 0.53 ± 0.70 (range 0-2). Ninety-six patients (56%) showed evidence of gland atrophy (meiboscore greater than 0) and the majority of patients (n=50, 29%) had a gland tortuosity score of 1. The mean BMI was 20.5 ± 4.86 kg/m 2 with 39.4% of patients (n = 69) above the 85th percentile. BMI percentile was not found to be a significant predictor of a meiboscore greater than 0 (odds ratio (OR) 1.004 95% confidence interval (CI) (0.99-1.10, p = 0.41). However, BMI percentile was found to be a significant predictor of gland tortuosity score (OR 1.01 95% CI (1.00-1.02), p = 0.02). Patients with BMI percentiles between 41 and 60 were 3.79 times more likely to have a gland tortuosity score of greater than 0 than patients with BMI percentiles between 0 and 20 (OR 3.789 CI (1.17-12.24)). No significant associations were found between age, race, or sex and meiboscore or tortuosity. There was a trend towards reduction in lipid layer thickness with increasing BMI percentile (p = 0.028, r 2  = 0.04)., Conclusion: In this pediatric population, there was an association between meibomian gland tortuosity and higher percentiles of BMI. Future studies are needed to elucidate the pathogenesis of meibomian gland tortuosity and atrophy in pediatric patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Macular images of infants with early-onset edema (occurring at or before 33 weeks' postmenstrual age [PMA]) and infants with late-onset edema (at or after 36 weeks' PMA) were compared. At first appearance, early-onset edema has a more severe morphology, with foveal bulging and elongated cystoid spaces than late-onset edema, which presents as small cystoid spaces outside the foveal center. Morphological variations may be an indicator of the underlying cause of edema in preterm infants. The presence of mostly parafoveal small cystoid spaces in the late-onset edema group may be suggestive of an association with neurological injury., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: Genipin has been proposed as a possible neuroprotective therapy in myopia and glaucoma. Here, we aim to determine the effects of prolonged genipin-induced scleral stiffening on visual function., Methods: Eyes from Brown Norway rats were treated in vivo with either a single 15 mM genipin retrobulbar injection or sham retrobulbar injection and were compared to naïve eyes. Intraocular pressure, optomotor response, and electroretinograms were repeatedly measured over 4 weeks following retrobulbar injections to determine visual and retinal function. At 4 weeks, we quantified retinal ganglion cell axon counts. Finally, molecular changes in gene and protein expression were analyzed via real-time polymerase chain reaction (RT-PCR) and proteomics., Results: Retrobulbar injection of genipin did not affect intraocular pressure (IOP) or retinal function, nor have a sustained impact on visual function. Although genipin-treated eyes had a small decrease in retinal ganglion cell axon counts compared to contralateral sham-treated eyes (-8,558 ± 18,646; mean ± SD), this was not statistically significant ( P = 0.206, n = 9). Last, we did not observe any changes in gene or protein expression due to genipin treatment., Conclusions: Posterior scleral stiffening with a single retrobulbar injection of 15 mM genipin causes no sustained deficits in visual or retinal function or at the molecular level in the retina and sclera. Retinal ganglion cell axon morphology appeared normal., Translational Significance: These results support future in vivo studies to determine the efficacy of genipin-induced posterior scleral stiffening to help treat ocular diseases, like myopia and glaucoma., Competing Interests: Disclosure: B.G. Hannon, None; C. Luna, None; A.J. Feola, None; M.D. Ritch, None; A.T. Read, None; S.S. Stinnett, None; H. Vo, None; M.T. Pardue, None; P. Ethier, None, (Copyright 2020 The Authors.)

Background: Previous epidemiologic studies have suggested an association between AMD and AD, and several therapeutic agents are being developed based on this principle. However, prior studies have provided conflicting results due in part to their reliance on clinical diagnoses that are not based on gold-standard histopathology., Objective: To use histopathologic standards for diagnosis in order to determine the co-prevalence of AD among patients with and without AMD., Methods: This is a cross-sectional study of 157 autopsy ocular specimens from patients with and without AMD that were greater than 75 years of age at death. Sarks staging was used to document the severity of AMD, and Braak and Braak staging was used to assess the severity of AD in corresponding brain specimens. The prevalence of AD within different severities of AMD was determined using univariable and multivariable logistic regression., Results: 58% of autopsy eyes had AMD. The prevalence of AD was lower in AMD subjects (63%) compared to non-AMD subjects (73%), even when grouped by severity (all p > 0.15). The likelihood of AD was significantly less in AMD subjects, even after adjusting for age and sex in multivariable analysis (OR 0.47, p = 0.049)., Conclusion: Histopathologic diagnoses fail to support an increase in prevalence of AD among subjects with AMD, even when disease severity is considered.

Purpose: To assess macular vasculature in healthy infants and children using OCT angiography (OCTA)., Design: Prospective cross-sectional study., Participants: One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center., Methods: We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes., Main Outcome Measures: The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC., Results: The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm 2 ; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R 2  = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R 2  = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00)., Conclusions: Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: This article describes treatment patterns and visual outcomes for central retinal vein occlusion (CRVO) in the antivascular endothelial growth factor (anti-VEGF) era., Methods: A retrospective cohort study of eyes diagnosed with CRVO between 2009 and 2016 was conducted. Treatment history and visual acuity (VA) measurements were abstracted from medical records and analyzed., Results: A total of 476 eyes of 476 patients (median age 67 years, median follow-up 25.4 months) were included. Optical coherence tomography was obtained in 93.9% and fluorescein angiography in 80% of cases on presentation. Mean VA at presentation and final visit was 20/60 and 20/94, respectively, for eyes with nonischemic CRVO, whereas that of ischemic cases remained worse than 20/800 at final follow-up. Intravitreal bevacizumab was the most common first treatment (42.2%). Intravitreal steroid was the first treatment in 3.6% and ultimately administered in 11.3% of eyes. In the first year, an average of 5.2 ± 3.6 and 2.2 ± 3.4 anti-VEGF injections were given in treatment-naive and nontreatment-naive eyes, respectively., Conclusions: In our real-world cohort, anti-VEGF injection burden and frequency are lower than in published clinical trials. Visual outcomes in both ischemic and nonischemic eyes with CRVO are poorer than expected and worse than those recorded in controlled trial settings., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Objectives: To evaluate a smartphone-based application's (Peek Acuity) ability to assess visual acuity and screen for ocular conditions in children, we compared visual acuity assessment between Peek Acuity and the pediatric ophthalmology examination and evaluated Peek Acuity's ability to identify children with referable ocular conditions., Study Design: We prospectively recruited 111 children age 3-17 years, presenting to a pediatric ophthalmology clinic, who could follow instructions. Monocular visual acuity assessments by Peek Acuity and standard clinical methods were performed in randomized order. We compared visual acuity assessments between methods using intraclass correlation coefficient (ICC) and evaluated Peek Acuity's ability to identify children with referable ocular conditions., Results: ICC comparing visual acuity assessed between methods was 0.88 (95% CI 0.83-0.92) for first and 0.85 (95% CI 0.78-0.89) for second eyes examined. ICC among 3 to 5-year-olds (preschool-age children) was 0.88 (95% CI 0.77-0.94) for first and 0.45 (95% CI 0.13-0.68) for second eyes examined. Peek Acuity had a sensitivity of 83%-86% for decreased vision and 69%-83% for referable ocular disease. Sensitivity was highest among 3 to 5-year-olds with decreased vision, 93%-100%., Conclusions: Overall, Peek Acuity visual acuity assessment correlated well with visual acuity assessed by standard clinical methods, though preschool-age children appeared more susceptible to examination fatigue. Peek Acuity performed adequately as a screening tool and had the greatest sensitivity among those with decreased vision and preschool-age children., Trial Registration: ClinicalTrials.gov: NCT03212222., (Copyright © 2019 Elsevier Inc. All rights reserved.)