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Purpose: To evaluate the association between a polygenic risk score (PRS) for primary open-angle glaucoma (POAG) and the age at the first trabeculectomy and the need for bilateral trabeculectomy., Design: Retrospective observational cohort study., Participants: Nine hundred and three genotyped participants with POAG from the Australian and New Zealand Registry of Advanced Glaucoma., Methods: The ocular surgical history of these participants was reviewed and the following parameters were recorded: age at diagnosis, age at trabeculectomy, and lateraly of trabeculectomy. Multivariate linear regression analyses correlated glaucoma PRSs with age at trabeculectomy, and laterality of trabeculectomy. For descriptive purposes, the participants were stratified into the top decile, intermediate group (10th-89th percentile), and bottom decile., Main Outcome Measures: Age at trabeculectomy, and laterality of trabeculectomy., Results: Higher PRS was associated with younger age at the first trabeculectomy (β, -1.94 years/standard deviation; 95% confidence interval [CI], - 0.41 to -3.47; P = 0.014). Participants in the top decile underwent their first trabeculectomy approximately 7 years earlier than participants in the lowest decile (mean difference, -7.04 years; 95% CI, 2.82-11.26). Participants in the top decile were 1.41-fold more likely to require bilateral trabeculectomy than participants in the bottom decile (odds ratio, 1.41; 95% CI, 1.06-1.91; P = 0.021)., Conclusions: This report identified clinically relevant correlations between glaucoma PRS and the need for surgical intervention in patients with glaucoma. Further work is required to investigate the association between PRS and other clinical end points such as treatment initiation., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Early diagnosis of open-angle glaucoma can lead to vision-saving treatment, and genetic variation is an increasingly powerful indicator in disease risk stratification., Objective: To compare polygenic and monogenic variants in risk of glaucoma., Design, Setting, and Participants: Clinical and genetic data were obtained for 2507 individuals from the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) and 411 337 individuals in cross-sectional cohort studies including individuals of European ancestry in the UK Biobank. Recruitment to the UK Biobank occurred between 2006 and 2010, and data analysis occurred between September 2019 and August 2020., Main Outcomes and Measures: Association of monogenic and polygenic variants with glaucoma risk., Results: Individuals at high polygenic risk, defined as those in the top 5% of an unselected population, had a glaucoma risk (odds ratio [OR], 2.77; 95% CI, 2.58-2.98) comparable with the risk among individuals heterozygous for the MYOC p.Gln368Ter variant (OR 4.19; 95% CI, 3.25-5.31), which is the most common single-gene variant known to cause primary open-angle glaucoma. High polygenic risk was more than 6 times more common than MYOC p.Gln368Ter heterozygosity in ANZRAG (15.7% vs 2.6%) and more than 15 times more common in the general population (5.0% vs 0.32%). Within ANZRAG, high polygenic risk was associated with a mean (SD) age at glaucoma diagnosis that did not differ from the age at glaucoma diagnosis among individuals heterozygous for MYOC p.Gln368Ter (57.2 [14.2] vs 54.8 [13.6] years; P > .99)., Conclusions and Relevance: Monogenic and high polygenic risk were each associated with a more than 2.5-fold increased odds of developing glaucoma and an equivalent mean age at glaucoma diagnosis, with high polygenic risk more than 15 times more common in the general population.