Prediction of Risk, Severity, and Progression of Primary Open-Angle Glaucoma in a Taiwanese Population Based on Polygenic Risk Scores.

OBJECTIVE Primary open-angle glaucoma (POAG) is the most common type of glaucoma worldwide and a leading cause of irreversible blindness. While polygenic risk scores (PRS) have shown promise for predicting POAG risk in European populations, their applicability in East Asian populations remains underexplored. We aimed to develop PRSs to predict the risk of developing POAG and evaluate their association with disease severity and progression in the Taiwanese population. DESIGN Population-based retrospective cohort study SUBJECTS: A total of 3,064 patients with POAG and 8,247 participants aged > 70 years without a glaucoma diagnosis were included. METHODS Genotypic and demographic data were collected from all participants. The PRS for POAG was constructed using summary statistics from a genome-wide association study. Associations between PRS and POAG risk were assessed using multivariate logistic regression to estimate odds ratios. Additional outcomes-medication burden, visual field performance, and longitudinal changes in retinal nerve fiber layer (RNFL) thickness-were analyzed to assess PRS correlation with disease severity and progression. MAIN OUTCOME MEASURES PRS, number of topical glaucoma medication classes used, visual field test results, and annual RNFL thinning rate. RESULTS Individuals in the top 10% of the PRS had a 1.64-fold increased risk of developing POAG (95% CI: 1.02-2.63; p = 0.042) compared with those in the lowest quartile. Among the patients with POAG, a higher mean PRS was significantly associated with the use of more than two classes of topical medications (p=0.024). Additionally, those in the top 50% of the PRS had an average annual decline of 1.79% in visual field index (β=-1.79; 95% CI: -0.14 to -0.01; p=0.048) compared with those in the bottom 50%. CONCLUSION The PRS developed in this study effectively predicted POAG risk and was associated with increased disease severity and rapid progression in a Taiwanese population. These findings highlight the potential of PRS as a clinical tool for early risk stratification, personalized treatment planning, and the optimization of follow-up intervals in glaucoma care.