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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.Retrospective observational cohort study.Nine hundred and three genotyped participants with POAG from the Australian and New Zealand Registry of Advanced Glaucoma.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.Age at trabeculectomy, and laterality of trabeculectomy.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).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.

A cross-sectional case study series of four individuals with biallelic pathogenic or likely pathogenicThe phenotypic spectrum across 91 individuals sourced from literature and four individuals from this case study series was highly variable. The main ocular phenotypes included ectopia lentis (95/95, 100%), ectopia lentis et pupillae (18/95, 19%), iris transillumination (13/95, 14%), iridodonesis (12/95, 13%), persistent pupillary membrane (12/95, 13%), and early-onset cataract or lens opacities (12/95, 13%). Anterior segment features other than ectopia lentis appeared to be exclusively associated with biallelic loss of function variants (p0.001). Pupillary block glaucoma had a prevalence of 1%. Post-lensectomy complications included retinal detachment (6/41, 15%), elevated intraocular pressure (4/41, 10%), and aphakic glaucoma (1/41, 2%). Most individuals were not reported to have had systemic features (69/95, 73%).The clinical phenotype of

ImportanceIrreversible vision loss from primary open-angle glaucoma (POAG) can be prevented through timely diagnosis and treatment, although definitive diagnosis can be difficult in early-stage disease. As a consequence, large numbers of individuals with suspected glaucoma require regular monitoring, even though many of these may never develop disease and other high-risk individuals with suspected glaucoma may have delayed or inadequate treatment. POAG is one of the most heritable common diseases, and this provides an opportunity to use genetic instruments in risk-stratified screening, diagnosis, and treatment of early glaucoma.ObjectiveTo assess the association of glaucoma polygenic risk with glaucoma progression in early-stage disease.Design, Setting, and ParticipantsThis cohort study used clinical and genetic data obtained from a longitudinal cohort study, Progression Risk of Glaucoma: Relevant SNPs With Significant Association (PROGRESSA). Participants of European ancestry with characteristic optic nerve head changes suggestive of glaucoma were included. Data were collected between February 2012 and June 2020. Analysis took place between July 2020 and April 2022.Main Outcomes and MeasuresThe association of a glaucoma polygenic risk score (PRS) (2673 uncorrelated variants) with rate of peripapillary retinal nerve fiber layer thinning on optical coherence tomography and progression of visual field loss on 24-2 Humphrey visual fields.ResultsA total of 1777 eyes from 896 individuals had sufficient data for structural progression analyses and 1563 eyes from 808 individuals for functional progression analyses. The mean (SD) age was 62.1 (9.9) years, 488 (44%) were male, and 1087 of 1103 individuals (98.5%) had European ancestry. An ancestrally matched normative population cohort (n = 17 642) was used for PRS reference. Individuals in the top 5% PRS risk group were at a higher risk of visual field progression compared with the remaining 95% after 5 years (hazard ratio, 1.5; 95% CI, 1.13-1.97; P = .005). Conversely, those in the bottom 20% PRS risk group were at a lower risk of visual field progression compared with an intermediate risk group over 3 years (hazard ratio, 0.52; 95% CI, 0.28-0.96; P = .04).Conclusions and RelevanceIn this study, high polygenic risk was associated with more rapid structural and functional progression in early POAG, despite more intensive treatment. A PRS may serve as a valuable adjunct to identify individuals who stand to benefit the most from more frequent surveillance and earlier or more intensive treatment.