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To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Cross-sectional analysis. Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. Proportion of patients with POAG after stratification according to the GRS. We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35–8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79–9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10–4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10–6). The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Objective: To investigate cellular-level morphological alterations in the retinal neuroglia in eyes with epiretinal membrane (ERM)., Design: Prospective cross-sectional, observational study (November 2020-May 2022)., Subjects and Controls: We included 41 eyes with unilateral idiopathic ERM and 33 healthy eyes of healthy volunteers., Methods: We examined the foveal microstructures in all eyes using adaptive optics OCT (AO-OCT) with axial and lateral resolutions of 3.4 and 3.0 μm, respectively. Adaptive optics OCT images were acquired for a 2.5° (728 μm) area at the foveal center., Main Outcome Measures: Foveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution units, and associations between these parameters., Results: Adaptive optics OCT imaging of healthy eyes and eyes with ERM revealed sharp hyperreflective lines of the external limiting membrane (ELM), accompanied by hyporeflective gaps, individual nuclei of the foveal cone photoreceptors, and Müller cell bodies. The arrangement of Müller cell bodies was more vertical in eyes with ERM than in normal eyes. Epiretinal membranes adhered to foveal Müller cells via the internal limiting membrane (ILM), exerting vertical traction that pulled the foveal cones anteriorly. Adaptive optics OCT also enabled visualization of outer segment (OS) discs. Hyperreflective changes in the OS discs were observed beneath the vertically thickened ellipsoid zone (EZ) in 15 eyes (36.6%) with ERM. For eyes with ERM, multiple regression analysis showed that the length from ILM to the inner border of the outer nuclear layer and the EZ thickness were significantly associated with BCVA (β = 5.3 × 10 -4 and 82.7 × 10 -4 , respectively), with associated 95% confidence intervals of 1.3 × 10 -4 to 9.3 × 10 -4 ( P  = 0.011) and 39.0 × 10 -4 to 126.5 × 10 -4 ( P  < 0.001), respectively. The EZ thickness was significantly and positively associated with the length from ELM to the retinal pigment epithelium (β = 23.9 × 10 -2 , 95% confidence interval: 4.8 × 10 -2 to 42.9 × 10 -2 ; P  = 0.015)., Conclusions: Cellular imaging of retinal neuroglia by AO-OCT may suggest possible mechanisms associated with visual impairment in patients with ERM, which could potentially contribute to the growing body of knowledge on its pathophysiology. However, these insights require further validation through extensive studies to fully ascertain their significance., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)