Abstract
Purpose :
Polygenic risk score (PRS) has been shown to help determine glaucoma progression, yet its role in predicting treatment outcomes remains underexplored. This study evaluates the association between a PRS for Primary Open Angle Glaucoma (POAG) and SLT results among glaucoma patients.
Methods :
SLT-treated glaucoma patients at Massachusetts Eye and Ear Infirmary in 2016-2022 were identified from electronic medical records. Genome-wide PRS for POAG was built usingdata from a large cross-ancestry genome-wide association study (GWAS) meta-analysis. Eyes were categorized into high (top 25%) and low (bottom 75%) PRS groups.Kaplan-Meier survival analysis was used to assess time to treatment failure, observed from six weeks to two years post-SLT. Failure was defined as less than 20% reduction in intraocular pressure (IOP), additional glaucoma medications, or subsequent SLT or surgery. Predictors of failure were analyzed using Cox proportional hazard models adjusted for age, gender, genetic ancestry, family history of glaucoma, glaucoma type, pre-SLT number of glaucoma medication, visual field mean deviation, and IOP. A sensitivity analysis was done on POAG given the PRS was developed for POAG.
Results :
The study included 72 eyes from 48 patients; 54 (75%) in the low PRS and 18 (25%) in the high PRS group. Glaucoma types were POAG (75%), pseudoexfoliation glaucoma (9.7%), normotension glaucoma (8.3%), and others (6.9%). Mean pre-treatment IOP was 17.84±4.7 mmHg for low PRS and 16.7±5.06 mmHg for high PRS (p=0.6). Failure rates at 6 and 12 months were 37% and 63% for low PRS, and 78% and 89% for high PRS, respectively (p=0.018). Failure was primarily due to insufficient IOP reduction (91% in low PRS and 100% in high PRS). There was a significant association between high PRS and SLT failure risk (HR 3.65, 95%CI 1.45—9.21, p=0.006). This finding was also observed in the POAG-only analysis (HR 8.05, 95%CI 2.8—23.10, p<0.001).
Conclusions :
Higher PRS is associated with a greater likelihood of SLT treatment failure in glaucoma patients. While the findings were consistent across the primary analysis and POAG-only sensitivity analysis, the overrepresentation of POAG highlights the need for further validation across a broader spectrum of glaucoma subtypes with larger sample size.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.