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Purpose: To determine the treatment patterns and outcomes of pediatric retinal detachments (RDs) associated with hereditary vitreoretinopathies., Design: Retrospective cohort analysis using IRIS® Registry (Intelligent Research in Sight) database., Participants: Patients < 18 years old with a rhegmatogenous RD and a systemic disorder associated with vitreoretinal degeneration (e.g., Stickler syndrome) or other malformation of the vitreous from 2013-2019., Methods: Cases were identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9, ICD-10) diagnostic codes from the IRIS® Registry cohort. Other hereditary vitreoretinopathies that are not encoded by specific ICD code(s) were captured by text search. Nonspecific vitreous abnormality ICD codes were also included. Exclusion criteria included traumatic retinal detachments using ICD codes for ocular trauma and serous or exudative retinal detachment. Surgical procedures were identified using Current Procedural Terminology (CPT) codes for repair of retinal detachment. Baseline demographic information collected included age, gender, race/ethnicity, geographic region of the provider location, and health insurance status., Main Outcome Measures: Main outcomes measured in this study were average time to first surgery, number of eyes presenting with bilateral detachments, and choice of initial surgical procedure., Results: A total of 2115 eyes of 1722 patients were identified (mean age, 10.4 years; 58% male). The median time to first surgery was 7 days (interquartile range, 40 days). One thousand four hundred seven eyes of 1134 patients had ≥ 1 year of follow-up, with 506 eyes (36%) developing a fellow eye RD. Thirty-three percent of patients presenting with bilateral detachments, and 349 eyes had initial RD surgery within 1 year of the index date documented by CPT code. Fellow eye detachment occurred a mean of 32 days after initial presentation. The mean number of surgeries per eye within 1 year was 1.68. Best-corrected visual acuity did not improve from a baseline 20/54 to 20/62. The initial procedure was most commonly complex RD repair (n = 176), followed by scleral buckle (n = 102), pars plana vitrectomy (n = 89), laser (n = 59), cryotherapy (n = 5), and pneumatic retinopexy (n = 5). There were 51 new diagnoses of glaucoma and 37 new diagnoses of aphakia within 1 year after the surgical procedure., Conclusions: IRIS Registry data provide insight into rare pediatric vitreoretinopathy-associated RDs, which have a high rate of reoperation and fellow eye involvement., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

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.

Objective: To image healthy retinal pigment epithelial (RPE) cells in vivo using Transscleral OPtical Imaging (TOPI) and to analyze statistics of RPE cell features as a function of age, axial length (AL), and eccentricity., Design: Single-center, exploratory, prospective, and descriptive clinical study., Participants: Forty-nine eyes (AL: 24.03 ± 0.93 mm; range: 21.9-26.7 mm) from 29 participants aged 21 to 70 years (37.1 ± 13.3 years; 19 men, 10 women)., Methods: Retinal images, including fundus photography and spectral-domain OCT, AL, and refractive error measurements were collected at baseline. For each eye, 6 high-resolution RPE images were acquired using TOPI at different locations, one of them being imaged 5 times to evaluate the repeatability of the method. Follow-up ophthalmic examination was repeated 1 to 3 weeks after TOPI to assess safety. Retinal pigment epithelial images were analyzed with a custom automated software to extract cell parameters. Statistical analysis of the selected high-contrast images included calculation of coefficient of variation (CoV) for each feature at each repetition and Spearman and Mann-Whitney tests to investigate the relationship between cell features and eye and subject characteristics., Main Outcome Measures: Retinal pigment epithelial cell features: density, area, center-to-center spacing, number of neighbors, circularity, elongation, solidity, and border distance CoV., Results: Macular RPE cell features were extracted from TOPI images at an eccentricity of 1.6° to 16.3° from the fovea. For each feature, the mean CoV was < 4%. Spearman test showed correlation within RPE cell features. In the perifovea, the region in which images were selected for all participants, longer AL significantly correlated with decreased RPE cell density (R Spearman, Rs = -0.746; P < 0.0001) and increased cell area (Rs = 0.668; P < 0.0001), without morphologic changes. Aging was also significantly correlated with decreased RPE density (Rs = -0.391; P  = 0.036) and increased cell area (Rs = 0.454; P  = 0.013). Lower circular, less symmetric, more elongated, and larger cells were observed in those > 50 years., Conclusions: The TOPI technology imaged RPE cells in vivo with a repeatability of < 4% for the CoV and was used to analyze the influence of physiologic factors on RPE cell morphometry in the perifovea of healthy volunteers., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2022 by the American Academy of Ophthalmology. Published by Elsevier Inc.)

Purpose: Microcystic macular edema (MME), also known as retrograde maculopathy (RM), is associated with severe optic atrophy because of a range of causes. However, similar changes have also been described in primary retinal pathology and the pathogenesis of MME is debated., Design: A retrospective observational case series., Participants: Patients with nonarteritic ischemic optic neuropathy., Methods: A retrospective observational case series was performed at the University Hospital of Liège, Belgium. The medical records of patients who were referred to our Neuro-ophthalmology department with a diagnosis of nonarteritic anterior ischemic optic neuropathy (NA-AION), between 2014 and 2021, were reviewed., Main Outcome Measures: Ganglion cell complex thickness, acute and chronic inner nuclear change., Results: In a cohort of 34 patients (mean age: 60 ± 12.5 years; 65.6% men) with NA-AION, we identified a transient microcystic change in the inner nuclear layer (INL) associated with optic disc swelling in 19 eyes at presentation. This early change was associated with a transudate of intraretinal and subretinal fluid originating from the optic disc. Among patients who had shown this transient change 3 subsequently developed MME, which remained fixed during the period of observation (range, 12-34 months). No MME was observed in patients without an early INL transient change. Microcystic macular edema was observed in patients with severe ganglion cell complex thinning at 6 months: mean (± SD) loss in superior hemimacula (-28.2 ± 5.2 μm [-33.3%, range, -22.3 to -30.3 μm]) and in inferior hemimacula (-30.7 ± 5.6 μm [-31.0%, range, -24.3 to 34.8 μm])., Conclusions: Our study has revealed 2 causes of INL cystic change in the same patients experiencing NA-AION, 1 reversible and the other likely permanent. This finding highlights the distinction between genuine edema related to transudation of fluid (in this case secondary to ischemic optic disc swelling) and the phenomenon observed in RM that is related to the degree of retinal nerve fiber layer/ganglion cell complex thinning. Cystic change in the INL is associated with severe optic atrophy (MME). However, similar changes have been described in  retinal  pathology and the pathogenesis of MME is debated., (© 2022 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Purpose: To describe the relationships between foveal structure and visual function in a cohort of individuals with foveal hypoplasia (FH) and to estimate FH grade and visual acuity using a deep learning classifier., Design: Retrospective cohort study and experimental study., Participants: A total of 201 patients with FH were evaluated at the National Eye Institute from 2004 to 2018., Methods: Structural components of foveal OCT scans and corresponding clinical data were analyzed to assess their contributions to visual acuity. To automate FH scoring and visual acuity correlations, we evaluated the following 3 inputs for training a neural network predictor: (1) OCT scans, (2) OCT scans and metadata, and (3) real OCT scans and fake OCT scans created from a generative adversarial network., Main Outcome Measures: The relationships between visual acuity outcomes and determinants, such as foveal morphology, nystagmus, and refractive error., Results: The mean subject age was 24.4 years (range, 1-73 years; standard deviation = 18.25 years) at the time of OCT imaging. The mean best-corrected visual acuity (n = 398 eyes) was equivalent to a logarithm of the minimal angle of resolution (LogMAR) value of 0.75 (Snellen 20/115). Spherical equivalent refractive error (SER) ranged from -20.25 diopters (D) to +13.63 D with a median of +0.50 D. The presence of nystagmus and a high-LogMAR value showed a statistically significant relationship ( P < 0.0001). The participants whose SER values were farther from plano demonstrated higher LogMAR values (n = 382 eyes). The proportion of patients with nystagmus increased with a higher FH grade. Variability in SER with grade 4 (range, -20.25 D to +13.00 D) compared with grade 1 (range, -8.88 D to +8.50 D) was statistically significant ( P < 0.0001). Our neural network predictors reliably estimated the FH grading and visual acuity (correlation to true value > 0.85 and > 0.70, respectively) for a test cohort of 37 individuals (98 OCT scans). Training the predictor on real OCT scans with metadata and fake OCT scans improved the accuracy over the model trained on real OCT scans alone., Conclusions: Nystagmus and foveal anatomy impact visual outcomes in patients with FH, and computational algorithms reliably estimate FH grading and visual acuity.

Purpose: To investigate the natural course of pachychoroid pigment epitheliopathy (PPE)., Design: A retrospective cohort study., Subjects: From the Kyoto central serous chorioretinopathy (CSC) cohort consisting of 548 patients with CSC as of September 2020, we included consecutive unilateral patients with acute or chronic CSC between January 2013 and December 2016., Methods: All patients underwent complete ophthalmic examination, including multimodal imaging such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. The fellow eyes of eyes diagnosed with CSC were screened for PPE, and their natural course was evaluated. We also evaluated the association of ARMS2 rs10490924, CFH rs800292 , TNFRSF10A rs13278062, and GATA5 rs6061548 genotypes with the natural course., Main Outcome Measures: Incidence of CSC, pachychoroid neovasculopathy, and pachychoroid geographic atrophy (GA)., Results: In total, 165 patients with unilateral CSC (mean age, 55.7 ± 12.6 years; female, 22.4%) were included from the Kyoto CSC cohort. Among them, 148 (89.7%) were diagnosed as having PPE in their non-CSC eye. Survival analysis revealed that 16.8% of PPE eyes developed CSC during the 6-year follow up, whereas non-PPE eyes did not. Although genetic factors did not have significant association with CSC development ( P  > 0.05, log-rank test), choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SFCT) were significantly associated with CSC incidence ( P  = 0.001, log-rank test). Survival analysis showed that eyes without CVH and eyes with SFCT < 300 μm did not develop CSC during the 6-year follow-up. Pachychoroid neovasculopathy developed in only 1 eye with PPE during a follow-up of 46.4 months. Pachychoroid GA did not develop in any of the studied eyes., Conclusions: This study revealed a natural history of PPE in a relatively large Japanese cohort. Choroidal vascular hyperpermeability and SFCT were significant risk factors for the development of CSC in PPE eyes. Although the current results cannot be generalized for all eyes with PPE, these findings present an important clinical implication., (© 2022 by the American Academy of Ophthalmology.)

Purpose: Clinical OCT angiography (OCTA) of the retinal microvasculature offers a quantitative correlate to systemic disease burden and treatment efficacy in sickle cell disease (SCD). The purpose of this study was to use the higher resolution of adaptive optics scanning light ophthalmoscopy (AOSLO) to elucidate OCTA features of parafoveal microvascular compromise identified in SCD patients., Design: Case series of 11 SCD patients and 1 unaffected control., Participants: A total of 11 eyes of 11 SCD patients (mean age, 33 years; range, 23-44; 8 female, 3 male) and 1 eye of a 34-year-old unaffected control., Methods: Ten sequential 3 × 3 mm parafoveal OCTA full vascular slab scans were obtained per eye using a commercial spectral domain OCT system (Avanti RTVue-XR; Optovue). These were used to identify areas of compromised perfusion near the foveal avascular zone (FAZ), designated as regions of interest (ROIs). Immediately thereafter, AOSLO imaging was performed on these ROIs to examine the cellular details of abnormal perfusion. Each participant was imaged at a single cross-sectional time point. Additionally, 2 of the SCD patients were imaged prospectively 2 months after initial imaging to study compromised capillary segments across time and with treatment., Main Outcome Measures: Detection and characterization of parafoveal perfusion abnormalities identified using OCTA and resolved using AOSLO imaging., Results: We found evidence of abnormal blood flow on OCTA and AOSLO imaging among all 11 SCD patients with diverse systemic and ocular histories. Adaptive optics scanning light ophthalmoscopy imaging revealed a spectrum of phenomena, including capillaries with intermittent blood flow, blood cell stasis, and sites of thrombus formation. Adaptive optics scanning light ophthalmoscopy imaging was able to resolve single sickled red blood cells, rouleaux formations, and blood cell-vessel wall interactions. OCT angiography and AOSLO imaging were sensitive enough to document improved retinal perfusion in an SCD patient 2 months after initiation of oral hydroxyurea therapy., Conclusions: Adaptive optics scanning light ophthalmoscopy imaging was able to reveal the cellular details of perfusion abnormalities detected using clinical OCTA. The synergy between these clinical and laboratory imaging modalities presents a promising avenue in the management of SCD through the development of noninvasive ocular biomarkers to prognosticate progression and measure the response to systemic treatment., (© 2022 by the American Academy of Ophthalmology.)

• This study evaluated the effects of two different mask types (Surgical mask and FFP2 mask) on choroidal thickness after 4 h of use. • We found choroidal thickness to increase after 4 h of mask use, and this increase was more marked in using an FFP2 mask. • The increase in subfoveal choroidal thickness in particular was statistically significant in using an FFP2 mask. To evaluate the choroidal thickness (CT) with enhanced depth-imaging optical coherence tomography (EDI-OCT) in healthcare professionals using surgical masks or FFP2 (N95) masks. We included the 120 eyes of 120 healthy volunteers who were using a surgical mask (Group 1) or FFP2 mask (Group 2) in the study. Spectral domain (SD) OCT was used to measure CT. EDI-OCT was used to measure subfoveal and perifoveal CT. Points 1500 μm nasal (C N1500) and temporal (C T1500) to the foveal center were used to measure perifoveal CT. Oxygen saturation and heart rate were measured with a pulse oximeter. All measurements were performed at 8:30, before wearing the mask, and at 12:30, when the mask was removed for the lunch break. Of a total of 120 subjects, Group 1 consisted of 60 subjects (mean age 38.50±8.60 (range 24–44) years) and Group 2 also consisted of 60 subjects (mean age 36.60±6.53 (range 26–45) years). Although not statistically significant, CT was seen to have increased at 3 measurement points in Group 1 after using the mask for 4 h: subfoveal CT (C SF) (p = 0.545), C T1500 (p = 0.080), and C N1500 (p = 0.251)). In Group 2, the increase in C SF (p = 0.001) was statistically significant while the increases in C N1500 and C T1500 were not (p = 0.162 and p = 0.058, respectively) after using the mask for 4 h. We found CT to increase after 4 h of mask use, and this increase was more marked in Group 2. The increase in subfoveal CT in particular was statistically significant in Group 2. [ABSTRACT FROM AUTHOR]

Purpose: To report patient characteristics and factors associated with poor visual acuity and abnormal intraocular pressure (IOP) in patients with scleritis in the American Academy of Ophthalmology's IRIS® Registry (Intelligent Research in Sight)., Design: Retrospective cohort study., Participants: Patients in the IRIS Registry with at least 3 office visits associated with an International Classification of Diseases scleritis code from 2013 through 2019., Methods: We evaluated demographic and clinical characteristics in scleritis and scleritis subtype cohorts. We conducted Cox proportional hazards and multiple logistic regression analyses to assess associations with poor best-corrected visual acuity (BCVA), vision loss, and IOP abnormalities., Main Outcome Measures: Patient characteristics, BCVA of 0.6 logarithm of the minimum angle of resolution (logMAR) or more, BCVA worsened by more than 3 logMAR units 6 months after presentation, IOP of 30 mmHg or more, and IOP of 5 mmHg or less., Results: In this cohort of 111 314 patients with scleritis, the mean ± standard deviation age was 58.5 ± 16.6 years, 66% were women, and 30% had bilateral scleritis. Patients with scleromalacia perforans were older and more likely to have bilateral disease. Multiple logistic regression analysis identified factors with increased odds for poor presenting BCVA (older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes) and at least 3 lines of vision loss 6 months after initial scleritis diagnosis (older age, smoking, and anterior scleritis). Cox proportional hazards regression modeling of BCVA of 0.6 logMAR or more showed older age (adjusted hazard ratio [aHR] per 10-year unit, 1.11), Black race (aHR, 1.19), Hispanic ethnicity (aHR, 1.22), active smoking (aHR, 1.39), former smoking (aHR, 1.26), and certain scleritis subtypes increase the risk of poor visual acuity development ( P < 0.001 for all). Older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes increased the odds of IOP abnormality., Conclusions: Older age, Black or Hispanic ancestry, smoking, and specific scleritis subtypes are risk factors for worse visual and IOP outcomes in patients with scleritis in the IRIS Registry. Closer follow-up may be appropriate for older, Black, or Hispanic patients with scleritis; smokers should receive smoking cessation assistance.

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.)

Background: Diabetes significantly increases the risk of postoperative macular edema (PME) after cataract surgery, leading to potential worst post-operative outcomes. This study aims to compare the effect of different prophylactic interventions in improving postoperative anatomic and visual acuity outcomes of diabetes patients who underwent cataract surgery., Methods: We searched MEDLINE, Embase, Web of Science databases from inception until February 2nd, 2022, for studies including studies reporting PME events and/or best-corrected visual acuity (BCVA) outcomes. Random-effects Bayesian network meta-analysis was performed to compare the efficiency of intravitreal anti-vascular endothelial growth factor injections (anti-VEGF), nonsteroidal anti-inflammatory drugs (NSAIDs) and topical steroids eye drop at 1 week, 1 month, 3 months, 6 months after cataract surgery., Findings: The total of 2566 participants from 17 randomized controlled trials were included in the network meta-analysis, with moderate risk of bias and no evidence of publication of bias. Compared to placebo/steroid eye drop alone, patients received additional topical NSAIDs or intravitreal anti-VEGF injections had lower risk of PME at 1 month (NSAIDs: OR=0·221, 95% Confidence interval [CI], 0·044-0·755, I 2 =0·0%, 5 studies; anti-VEGF: OR=0·151, 95%CI, 0·037-0·413, I 2 =0·0%, 5 studies) and 3 month (NSAIDs: OR=0·370, 95%CI, 0·140-0·875, I 2 =0·0%, 8 studies; anti-VEGF: OR=0·203, 95%CI, 0·101-0·353, I 2 =0·0%, 4 studies) after cataract surgery. Further, additional anti-VEGF exhibited better BCVA outcome at 1 month (mean difference of LogMAR: -0·083, 95%CI, -0·17 to -0·014, I 2 =62·0%, 5 studies), and 3 months (mean difference of LogMAR: -0·061, 95%CI, -0·11 to -0·011, I 2 =0·0%, 5 studies) after cataract surgery. Such additional benefits did not reach statistic significant at 6 months after surgery., Interpretation: Our data suggests that compared to placebo/steroid eye drop alone, additional prophylactic anti-VEGF intervention could be considered for preventing the occurrence of PME after cataract surgery in patients with diabetes., Funding: Research and Development of Special (2020-1-2052); Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045, Z181100001818003)., Competing Interests: None., (© 2022 The Author(s).)

Purpose: The impact of cataract surgery on low luminance visual acuity deficit (LLVAD) measurements was investigated by measuring the LLVAD before and after cataract surgery., Design: Prospective, longitudinal study., Participants: Patients undergoing cataract surgery., Methods: Photopic luminance (PL)-best-corrected visual acuity (BCVA) and low luminance (LL)-BCVA were obtained using the ETDRS chart. Low luminance visual acuity deficit scores were calculated by subtracting the LL-BCVA letter score from the PL-BCVA letter score. To demonstrate the reproducibility of these visual acuity measurements, we used data from drusen-only eyes previously published in the Complement Inhibition with Eculizumab for the Treatment of Nonexudative Age-Related Macular Degeneration (COMPLETE) study. The PL-BCVA, LL-BCVA, and LLVAD measurements obtained at an interval of 3 months in this cohort were used for comparison. In the current study, the impact of cataract surgery on LLVAD measurements was analyzed by comparing the PL-BCVA, LL-BCVA, and LLVAD measurements before and after cataract surgery., Main Outcome Measures: The reproducibility of the visual acuity measurements and the changes in LLVAD measurement after cataract surgery., Results: In the COMPLETE study, no clinically significant differences were found in the PL-BCVA, LL-BCVA, or LLVAD measurements between baseline and the 3-month follow-up visits with a change of -1.1 letters, -1.3 letters, and 0.1 letters, respectively ( P  = 0.02, P  = 0.11, and P  = 0.88, respectively). In the current study, significant increases were found in the PL-BCVA and LL-BCVA measurements, with a change of 7.3 letters and 10.2 letters after cataract surgery ( P < 0.001 for both), and a statistically significant decrease in LLVAD measurements was found, with a change of -3.0 letters after cataract surgery ( P  = 0.002)., Conclusions: Because of the variable effect of cataracts on LL-BCVA measurements and the significant change in LLVAD measurements after cataract surgery, investigators should be aware that cataract surgery during a trial will have an unpredictable impact on LLVAD measurements, and pseudophakic and phakic patients should be analyzed separately., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Purpose: To establish the safety, tolerability, pharmacokinetics, and pharmacodynamics of an intravitreal injection of recombinant human complement factor H (CFH), GEM103, in individuals with genetically defined age-related macular degeneration (AMD) and geographic atrophy (GA)., Design: Phase I single ascending-dose, open-label clinical trial (ClinicalTrials.gov identifier, NCT04246866)., Participants: Twelve individuals 50 years of age or older with a confirmed diagnosis of foveal GA in the study eye., Methods: Participants were assigned to the increasing dose cohorts and received 1 50-μl intravitreal injection of GEM103 at doses of 50 μg/eye, 100 μg/eye, 250 μg/eye, or 500 μg/eye; dose escalation was dependent on the occurrence of dose-limiting toxicities., Main Outcome Measures: Safety assessments included ocular and systemic adverse events (AEs), ocular examinations, clinical laboratory and vital signs, and serum antidrug antibody levels. Biomarkers, measured in the aqueous humor (AH), included CFH and complement activation biomarkers factor Ba and complement component 3a., Results: No dose-limiting toxicities were reported, enabling escalation to the maximum study dose. No anti-GEM103 antidrug antibodies were detected during the study. Four participants experienced AEs; these were nonserious, mild or moderate in severity, and unrelated to GEM103. The AEs in 2 of these participants were related to the intravitreal injection procedure. No clinically significant ophthalmic changes and no ocular inflammation were observed. Visual acuity was maintained and stable throughout the 8-week follow-up period. No choroidal neovascularization occurred. CFH levels increased in a dose-dependent manner after GEM103 administration with supraphysiological levels observed at week 1; levels were more than baseline for 8 weeks or more in all participants receiving single doses of 100 μg or more. Complement activation biomarkers were reduced 7 days after dose administration., Conclusions: A single intravitreal administration of GEM103 (up to 500 μg/eye) was well tolerated in individuals with GA. Of the few mild or moderate AEs reported, none were determined to be related to GEM103. No intraocular inflammation or choroidal neovascularization developed. CFH levels in AH were increased and stable for 8 weeks, with pharmacodynamic data suggesting that GEM103 restored complement regulation. These results support further development in a repeat-dose trial in patients with GA with AMD., (© 2022 by the American Academy of Ophthalmology.)

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., (© 2022 by the American Academy of Ophthalmology.)

Purpose: To study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade., Design: Evaluation of a diagnostic technology., Methods: We compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure-function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA)., Main Outcome Measures: Percentage area under the receiver operator characteristic curve (AUC) and Hedge's g effect size., Results: Acuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge's g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well., Conclusions: The rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes., (© 2022 by the American Academy of Ophthalmology.)

Purpose: To develop and validate an automated deep learning (DL)-based artificial intelligence (AI) platform for diagnosing and grading cataracts using slit-lamp and retroillumination lens photographs based on the Lens Opacities Classification System (LOCS) III., Design: Cross-sectional study in which a convolutional neural network was trained and tested using photographs of slit-lamp and retroillumination lens photographs., Participants: One thousand three hundred thirty-five slit-lamp images and 637 retroillumination lens images from 596 patients., Methods: Slit-lamp and retroillumination lens photographs were graded by 2 trained graders using LOCS III. Image datasets were labeled and divided into training, validation, and test datasets. We trained and validated AI platforms with 4 key strategies in the AI domain: (1) region detection network for redundant information inside data, (2) data augmentation and transfer learning for the small dataset size problem, (3) generalized cross-entropy loss for dataset bias, and (4) class balanced loss for class imbalance problems. The performance of the AI platform was reinforced with an ensemble of 3 AI algorithms: ResNet18, WideResNet50-2, and ResNext50., Main Outcome Measures: Diagnostic and LOCS III-based grading prediction performance of AI platforms., Results: The AI platform showed robust diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.9992 [95% confidence interval (CI), 0.9986-0.9998] and 0.9994 [95% CI, 0.9989-0.9998]; accuracy, 98.82% [95% CI, 97.7%-99.9%] and 98.51% [95% CI, 97.4%-99.6%]) and LOCS III-based grading prediction performance (AUC, 0.9567 [95% CI, 0.9501-0.9633] and 0.9650 [95% CI, 0.9509-0.9792]; accuracy, 91.22% [95% CI, 89.4%-93.0%] and 90.26% [95% CI, 88.6%-91.9%]) for nuclear opalescence (NO) and nuclear color (NC) using slit-lamp photographs, respectively. For cortical opacity (CO) and posterior subcapsular opacity (PSC), the system achieved high diagnostic performance (AUC, 0.9680 [95% CI, 0.9579-0.9781] and 0.9465 [95% CI, 0.9348-0.9582]; accuracy, 96.21% [95% CI, 94.4%-98.0%] and 92.17% [95% CI, 88.6%-95.8%]) and good LOCS III-based grading prediction performance (AUC, 0.9044 [95% CI, 0.8958-0.9129] and 0.9174 [95% CI, 0.9055-0.9295]; accuracy, 91.33% [95% CI, 89.7%-93.0%] and 87.89% [95% CI, 85.6%-90.2%]) using retroillumination images., Conclusions: Our DL-based AI platform successfully yielded accurate and precise detection and grading of NO and NC in 7-level classification and CO and PSC in 6-level classification, overcoming the limitations of medical databases such as few training data or biased label distribution., (© 2022 by the American Academy of Ophthalmology.)

Purpose: Faricimab is a novel anti-angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) bispecific antibody with high affinities and specificities for both VEGF and angiopoietin-2. It is postulated that targeting angiogenic factors and inflammatory pathways in addition to the VEGF pathway will increase treatment durability and improve outcomes. The phase 3 YOSEMITE (ClinicalTrials.gov identifier, NCT03622580) and RHINE (ClinicalTrials.gov identifier, NCT03622593) trials are designed to assess efficacy, safety, and durability of faricimab compared with aflibercept in patients with diabetic macular edema (DME). The trials evaluate a personalized treatment interval (PTI) approach to address heterogeneity in treatment response among patients with DME., Design: Two identically designed, global, double-masked, randomized, controlled phase 3 trials (YOSEMITE and RHINE)., Participants: Adults with center-involving DME secondary to type 1 or 2 diabetes mellitus., Methods: These studies were designed to evaluate 3 treatment groups: faricimab 6.0 mg dosed either at fixed dosing every 8 weeks after initial treatment with 6 intravitreal doses at 4-week intervals, or faricimab 6.0 mg dosed according to PTI after initial treatment with 4 every-4-week doses, compared with aflibercept 2.0 mg dosed every 8 weeks after 5 initial every-4-week doses. The primary end point of the studies was change from baseline in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Secondary end points included anatomic, durability, and patient-reported outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. The PTI is a protocol-defined flexible regimen based on the treat-and-extend concept, which allowed up to every-16-week adjustable dosing based on objective and standardized criteria. The PTI design aimed to maximize therapeutic results while minimizing treatment burden., Main Outcome Measures: We describe the rationale for the study design and the novel PTI (up to every-16-week adjustable dosing) approach for treatment with faricimab., Results: YOSEMITE and RHINE enrolled 940 and 951 patients, respectively. Results from each study will be reported separately., Conclusions: YOSEMITE and RHINE were the first registrational trials in retinal disease to incorporate an objective PTI regimen, allowing for up to every-16-week adjustable dosing with a dual angiopoietin-2 and VEGF-A inhibitor, faricimab 6.0 mg, for treatment of DME., (© 2021 by the American Academy of Ophthalmology.)

Purpose: To assess safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with intermediate age-related macular degeneration (AMD) and high-risk drusen (HRD) and to perform exploratory analyses of change in visual function., Design: Phase 1, single-center, open-label, 24-week clinical trial with preplanned HRD cohort., Participants: Adult patients ≥55 years of age with intermediate AMD and HRD., Methods: Participants received subcutaneous elamipretide 40 mg daily, with safety and tolerability assessed throughout the study. Ocular assessments included normal-luminance best-corrected visual acuity (BCVA), low-luminance best-corrected visual acuity (LLVA), normal-luminance binocular reading acuity (NLRA), low-luminance binocular reading acuity (LLRA), spectral-domain OCT, fundus autofluorescence (FAF), mesopic microperimetry, dark adaptation, and low-luminance questionnaire (LLQ)., Main Outcome Measures: The primary end point was safety and tolerability. Prespecified exploratory end points included changes from baseline in BCVA, LLVA, NLRA, LLRA, retinal pigment epithelium (RPE)-drusen complex (DC) volume by OCT, FAF, mesopic microperimetry, dark adaptation, and LLQ results., Results: Subcutaneous administration of elamipretide was highly feasible. All participants with HRD (n = 21) experienced 1 or more adverse events (AEs), but all were mild (57%) or moderate (43%), with the most common events related to injection site reactions. No serious systemic AEs occurred. One participant discontinued because of injection site reaction, 1 participant withdrew because they did not wish to continue study visits, and 1 participant withdrew after experiencing transient visual impairment. Among the 18 participants who completed the study, mean change in BCVA from baseline to 24 weeks was +3.6 letters ( P = 0.014) and LLVA was +5.6 letters ( P = 0.004). Compared with baseline, mean NLRA improved by -0.11 logarithm of the minimum angle of resolution (logMAR) units ( P = 0.001), and LLRA by -0.28 logMAR units ( P < 0.0001). Significant improvements were found in 6 of 7 subscales of the LLQ ( P < 0.0015). No significant changes were observed for RPE-DC volume, FAF, mesopic microperimetry, or dark adaptation., Conclusions: Elamipretide appeared to be generally safe and well tolerated in treating intermediate AMD and HRD. Exploratory analyses demonstrate a positive effect on visual function, particularly under low-luminance conditions. Further study of elamipretide for treatment of intermediate AMD with HRD is warranted., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Purpose: Assess the safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with dry age-related macular degeneration (AMD) and noncentral geographic atrophy (NCGA) and to perform exploratory analyses of change in visual function., Design: Phase 1, single-center, open-label, 24-week clinical trial with preplanned NCGA cohort., Participants: Adults ≥ 55 years of age with dry AMD and NCGA., Methods: Participants received subcutaneous elamipretide 40-mg daily; safety and tolerability assessed throughout. Ocular assessments included normal-luminance best-corrected visual acuity (BCVA), low-luminance BCVA (LLBCVA), normal-luminance binocular reading acuity (NLBRA), low-luminance binocular reading acuity (LLBRA), spectral-domain OCT, fundus autofluorescence (FAF), and patient self-reported function by low-luminance questionnaire (LLQ)., Main Outcome Measures: Primary end point was safety and tolerability. Prespecified exploratory end-points included changes in BCVA, LLBCVA, NLBRA, LLBRA, geographic atrophy (GA) area, and LLQ., Results: Subcutaneous elamipretide was highly feasible. All participants (n = 19) experienced 1 or more nonocular adverse events (AEs), but all AEs were either mild (73.7%) or moderate (26.3%); no serious AEs were noted. Two participants exited the study because of AEs (conversion to neovascular AMD, n = 1; intolerable injection site reaction, n = 1), 1 participant discontinued because of self-perceived lack of efficacy, and 1 participant chose not to continue with study visits. Among participants completing the study (n = 15), mean ± standard deviation (SD) change in BCVA from baseline to week 24 was +4.6 (5.1) letters ( P = 0.0032), while mean change (SD) in LLBCVA was +5.4 ± 7.9 letters ( P = 0.0245). Although minimal change in NLBRA occurred, mean ± SD change in LLBCVA was -0.52 ± 0.75 logarithm of the minimum angle of resolution units ( P = 0.005). Mean ± SD change in GA area (square root transformation) from baseline to week 24 was 0.14 ± 0.08 mm by FAF and 0.13 ± 0.14 mm by OCT. Improvement was observed in LLQ for dim light reading and general dim light vision., Conclusions: Elamipretide seems to be well tolerated without serious AEs in patients with dry AMD and NCGA. Exploratory analyses demonstrated possible positive effect on visual function, particularly under low luminance. A Phase 2b trial is underway to evaluate elamipretide further in dry AMD and NCGA., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Purpose: To define the role of optociliary shunt vessels (OSVs) in eyes with central retinal vein occlusion (CRVO) using OCT angiography (OCTA) with macular parameters., Design: Retrospective, observational, consecutive case series., Participants: Forty-one eyes in 38 consecutive patients with CRVO were analyzed in this study., Methods: Optic disc and macula were imaged by swept-source OCTA (3 × 3 mm) as well as by high-quality fundus photography., Main Outcome Measures: We compared macular vessel density (VD) and visual acuity between eyes in which OSVs developed and those in which they did not. Furthermore, we measured the diameter of the OSVs and analyzed the correlation with macular VD and visual acuity., Results: Optociliary shunt vessels were found in 25 eyes (61%). Central retinal vein occlusion with OSVs did not show any statistical difference compared with CRVO without OSVs in either macular VD of the total retina (0.31 ± 0.07 and 0.26 ± 0.09, respectively; P  = 0.0937) or final best-corrected visual acuity (BCVA) (0.30 ± 0.43 logarithm of the minimum angle of resolution [logMAR] and 0.59 ± 0.54 logMAR, respectively; P  = 0.0705). The mean OSV diameter was 71 ± 30 μm in CRVO with OSV. The diameter of the OSVs was correlated positively with superficial VD ( r  = 0.443; P  = 0.027), deep VD ( r  = 0.494; P  = 0.012), and total VD ( r  = 0.491; P  = 0.013). Furthermore, the OSV diameter was also negatively correlated with BCVA (logMAR) at the final visit ( r  = -0.531; P  = 0.006)., Conclusions: The results demonstrated that the diameter of the OSVs was associated with macular VD and visual acuity in patients with CRVO. The development of large OSVs on the optic disc may be a good indicator of the maintenance of blood flow in the macula., (© 2021 by the American Academy of Ophthalmology.)

Purpose: To describe the design and rationale of the phase 3 TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) trials that aimed to assess efficacy, safety, and durability of faricimab, the first bispecific antibody for intraocular use, which independently binds and neutralizes both angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A) versus aflibercept in patients with neovascular age-related macular degeneration (nAMD)., Design: Identical, global, double-masked, randomized, controlled, phase 3 clinical trials., Participants: Adults with treatment-naïve nAMD., Methods: These trials were designed to evaluate patients randomized to receive faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses. The initial doses in the faricimab arm were followed by individualized fixed treatment intervals up to week 60, based on disease activity assessment at weeks 20 and 24, guided by central subfield thickness, best-corrected visual acuity (BCVA), and investigator assessment. The primary efficacy end point was BCVA change from baseline averaged over weeks 40, 44, and 48. Secondary end points included the proportion of patients receiving every-8-week, every-12-week, and every-16-week faricimab and anatomic outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. From week 60, faricimab-treated patients followed a personalized treatment interval (PTI), a novel protocol-driven treat-and-extend regimen with interval adjustment from every 8 weeks to every 16 weeks based on individualized treatment response measured by anatomic criteria, functional criteria, and investigator assessment of patients' disease activity., Main Outcome Measures: Rationale for trial design and PTI approach., Results: The TENAYA and LUCERNE trials were the first registrational trials in nAMD to test fixed dosing regimens up to every 16 weeks based on patients' disease activity in year 1 and incorporate a PTI paradigm during year 2. The PTI approach was designed to tailor treatment intervals to individual patient needs, to reflect clinical practice treatment practice, and to reduce treatment burden., Conclusions: The innovative trial design rationale for the TENAYA and LUCERNE trials included maximizing the benefits of angiopoietin-2 blockade through dosing up to every 16 weeks and PTI regimens based on patients' disease activity while fulfilling health authority requirements for potential registrational efforts., (© 2021 by the American Academy of Ophthalmology.)

Purpose: To evaluate the safety and preliminary efficacy of THR-687 in patients with center-involved diabetic macular edema (DME)., Design: Phase 1, open-label, multicenter, 3 + 3 dose-escalation study with 3-month follow-up., Participants: Patients 18 years of age or older with visual impairment resulting from DME., Methods: Single intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg)., Main Outcome Measures: The primary outcome measure was the incidence of dose-limiting toxicities (DLTs). The secondary outcome measure was the incidence of adverse events (AEs), including the occurrence of laboratory abnormalities. Exploratory outcome measures included changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), assessments of ischemia and leakage on fluorescein angiography, and THR-687 levels in plasma., Results: Twelve patients were treated: 3 patients received 0.4 mg of THR-687, 3 patients received 1.0 mg of THR-687, and 6 patients received 2.5 mg of THR-687. Most patients were men (9/12 patients). Their mean age was 57.8 years. No DLTs or serious AEs were reported at any of the dose levels tested. Overall, 9 AEs in the study eye were reported for 5 of 12 patients. Of those, 4 AEs in 3 of 12 patients were deemed treatment related by the investigator, all of which were mild, started on the day of the injection, and had resolved within 28 days without treatment. Overall, mean gains from baseline in BCVA were observed at all study visits with a rapid onset (7.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters at day 7) and a durability up to the end of the study (8.3 ETDRS letters at month 3). A mean decrease in CST was observed up to month 1. Overall, the mean BCVA gains and CST decreases were highest at the highest THR-687 dose level tested. THR-687 was undetectable in plasma at 7 days after the injection., Conclusions: At all dose levels tested, a single intravitreal injection of THR-687 was safe and well tolerated. Preliminary efficacy was observed by a rapid gain in BCVA with 3 months' durability and a decrease in CST up to 1 month after the injection., (© 2021 by the American Academy of Ophthalmology.)

Purpose: To describe the prevalence, risk factors, and associations of vitreoretinal interface (VRI) abnormalities in a population-based study of older adults., Design: Cross-sectional analysis of cohort study participants., Participants: Of the 1149 participants (mean age, 76.1 ± 6.9 years) in the 15-year Blue Mountains Eye Study follow-up examination from 2007 through 2009, 905 (1791 eyes) had gradable time-domain or spectral-domain OCT scans of the macula from at least 1 eye., Methods: OCT scans were graded according to the International Vitreomacular Traction Study Group classification system of VRI abnormalities. Best-corrected visual acuity (BCVA) was recorded., Main Outcome Measures: Prevalence of VRIs., Results: Overall, 451 participants showed any VRI abnormality (49.8%). Prevalence of VRI abnormality by person was: vitreomacular adhesion (VMA), 33.6%; vitreomacular traction (VMT), 1.6%; epiretinal membrane (ERM), 21.4%; full-thickness macular hole (FTMH), 0.7%; and lamellar macular hole (LMH), 0.7%. Twenty-two percent of VMAs were focal, and 78% were broad based; 76% of VMTs were focal, and 24% were broad based. All FTMHs observed were large (>400 μm), with mean aperture size of 573 μm (range, 459-771 μm). Increased age was associated with higher ERM and lower VMA prevalence ( P < 0.001 for both). Pseudophakia and myopia were associated with ERM (age- and sex-adjusted odds ratios [ORs], 1.48 [95% confidence interval (CI), 1.01-2.17] and 1.72 [95% CI, 1.05-2.81], respectively). Moderate or severe ERM and FTMH were associated with worse BCVA of 9.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI, 3.4-15.0 ETDRS letters; P  = 0.008) and 26.0 ETDRS letters (95% CI, 10.9-41.1 ETDRS letters; P  = 0.001), respectively., Conclusions: The prevalence of VRI abnormalities is high in older individuals. Epiretinal membrane was associated with increasing age, pseudophakia, and myopia. Epiretinal membrane and FTMH may account for significant visual loss in the affected eye. This study provided useful population-based data on the prevalence of VRI abnormalities in older individuals., (© 2021 by the American Academy of Ophthalmology.)

Purpose: To report visual outcomes and rate of retinal pigment epithelium (RPE) atrophy progression in patients with extensive macular atrophy with pseudodrusen-like appearance (EMAP)., Design: Retrospective, observational study., Participants: Patients with EMAP and symptom onset before 55 years of age, at least 12 months of follow-up using Spectralis blue-light fundus autofluorescence (BAF) and OCT and with no other ocular or systemic conditions., Methods: Best-corrected visual acuity (BCVA), BAF, and OCT images were reviewed at baseline and at each annual visit until the last available follow-up. Atrophy was measured by 2 graders using the region finder software on Heidelberg Explorer and confirmed using OCT scans covering the entire atrophic lesion. The following imaging biomarkers were analyzed at each visit: foveal atrophy, vitreomacular traction, outer retinal tubulations, choroidal caverns and subfoveal choroidal thickness, border autofluorescence pattern (hyper-autofluorescent or iso-autofluorescent), and border irregularity as expressed by circularity index (CI)., Main Outcome Measures: Primary outcomes were annual rate of atrophy enlargement and BCVA loss in EMAP patients. Secondary outcomes included the assessment of potential factors able to predict disease progression., Results: Thirty-six eyes from 18 patients with EMAP (6 men [33%]; mean age at symptom onset, 48.1 ± 1.7 years) were included. Mean follow-up lasted 32.8 ± 14.3 months. RPE atrophy increased from 10.8 ± 6.3 mm 2 at baseline to 18.1 ± 8.3 mm 2 at the end of follow-up, with a rate of 2.91 ± 1.09 mm 2 /year. Faster progression was associated with smaller CI at baseline ( P  = 0.02) and with iso-autofluorescent lesion borders ( P  = 0.01). Visual acuity declined progressively at a rate of 7.4 ± 5.8 letters per year, with 57% of eyes showing vision of 20/200 Snellen or worse at the 4-year follow-up. Worse visual outcomes were observed in patients with early foveal involvement at baseline ( P  = 0.02)., Conclusions: Patients affected by EMAP present a rapid expansion of RPE atrophy that is comparable with the diffuse-trickling form of geographic atrophy. More irregular and iso-autofluorescent lesion borders seem to predict faster progression. Our findings may provide relevant information for patient counseling and future interventional approaches to select the best candidates and proper clinical outcomes., (© 2021 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)