Study: Polygenic Risk Score for Glaucoma Impacts Prognosis

According to a new study, the top-performing published PRS for glaucoma provides a more precise risk assessment than family history alone and “was effective in stratifying individuals based on several prognostic measures, including medical treatment escalation and surgical interventions,” the authors reported. Photo: Brian D. Fisher, OD. Click image to enlarge. Given the highly heritable nature of glaucoma, several polygenic risk scores (PRSs) have been developed to improve risk stratification; however, the clinical utility of these tools remains ambiguous. Researchers from MIT, Massachusetts General Hospital and the University of Helsinki recently scoured the literature to assess how several published glaucoma PRSs perform in estimating glaucoma risk, age at onset and prognosis. They found that the top-performing PRS could not only help clinicians identify who is most likely to develop glaucoma but also which individuals may develop it earlier and who may require more intensive treatment.The researchers benchmarked 14 published scores drawn from the Polygenic Score Catalog and then tested the top performer in a national biobank setting. The study included 21,609 people with glaucoma diagnosed after age 40. Participants came from FinnGen, a large Finnish resource linking genotyping data with nationwide hospital, medication reimbursement and prescription registers. Follow-up continued through age 85.The best-performing PRS was one developed by Truong et al. Compared with the average-risk group (20th to 80th percentile), individuals in the top 10% of the PRS distribution had a hazard ratio of 3.32 for glaucoma. Risk rose dramatically at the extremes: cumulative lifetime glaucoma incidence by age 85 was 2.5% in those below the 1st percentile, 31.9% in the 95th to 99th percentile and 45.3% in the ≥99th percentile group. Among people with average PRS, lifetime risk was 11.3%.High genetic risk also translated into earlier disease. By age 60, the average population reached a cumulative incidence of 1.6%, while those with high PRS reached that level much earlier: age 46.2 in the ≥99th percentile and age 48.6 in the 95th to 99th percentile group. Those in the lowest percentile reached the same threshold only at age 73.3.Family history mattered, but the authors found that this information alone “is insufficient for capturing genetic susceptibility to glaucoma.” When family history was added to the PRS model, the PRS effect size dropped by only 4.2%. When PRS was added to family history, the family history effect size dropped by 12.3%. In other words, the two factors contributed independently, but the patient’s own PRS gave a more precise risk estimate. The study also revealed “that a high PRS is associated with several aspects of glaucoma severity, such as higher rates of treatment escalation and procedures,” the authors reported. PRS was most informative for POAG, with weaker performance for normal-tension and exfoliation glaucoma. It also predicted a more difficult treatment course; over 20 years after diagnosis, the highest PRS decile had higher cumulative incidences of medication escalation (60.6% vs. 38.4%), laser therapy (39.8% vs. 22.9%) and incisional surgery (15.8% vs 9.5%) compared with the lowest PRS decile. The highest PRS decile also had more glaucoma-related visits and higher median costs.“Despite the impact on prognosis, current PRSs are primarily developed to predict disease risk rather than prognosis,” the researchers commented in their paper. They argued, “Future research should therefore aim to develop glaucoma PRSs that better target stratification of disease severity and prognosis.”The authors highlighted several noteworthy limitations of their research, including the predominantly European-ancestry population, which reduces generalizability to more diverse groups. Moreover, treatment patterns have changed over time, which could affect comparisons across the 20-year follow-up. Finally, the study is observational, meaning it shows association rather than proving that PRS-guided care improves outcomes.“Combining PRS with clinical factors and imaging biomarkers across diverse ancestries will be essential for clinical applicability, as many published PRSs show heterogeneity in performance across ancestries and cohorts,” the researchers concluded. “Importantly, randomized prospective studies are needed to evaluate the optimal integration and screening intervals for bringing glaucoma PRSs into clinical practice, alongside assessment of cost-effectiveness.”Click here for the journal source. Tusa ES, Tamlander M, Ripatti S, et al. Polygenic risk impacts lifetime risk and prognosis of glaucoma. Ophthalmol. June 10, 2026. [Epub ahead of print] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.