Genetic risk for open angle glaucoma subtypes is associated with specific visual field defect classes

Abstract

Purpose : Identify visual field (VF) archetypes associated with genetic risk for primary open angle glaucoma (POAG) and its subtypes, high-tension glaucoma (HTG) and normal-tension glaucoma (NTG).

Methods : Archetypal analysis was performed on 263,707 VF from 34,331 patients with a H40.1x code seen at Massachusetts Eye and Ear from 2012-2022. Analysis output was 9 optimal VF archetype coefficients. POAG polygenic risk score (PRS), NTG PRS, and weighted HTG genetic risk score (GRS) weights were trained based on large genome-wide association studies in the Mass General Brigham Biobank and calculated for those with available genotype data. Linear and logistic regressions were used to test for correlation of the risk scores with VF archetype coefficients and defect class, correcting for age, sex, and ancestry.

Results : Among 719 patients (810 eyes, 4,335 VFs), higher POAG PRS was associated with higher coefficients for archetype (AT) 3 (b=0.008), 4 (b=0.005), 6 (b=0.005), 7 (b=0.006), 8 (b=0.004), and 9 (b=0.002) (p<0.01 for all). NTG PRS was associated with AT 2 (b=0.014), 3 (b=0.024), 4 (b=0.008), and 6 (b=0.023) (p<0.001 for all, except A4 p=0.026), while HTG GRS was associated with AT 1(b=0.013) and 8 (b=0.016) (p<0.001 for both) (Fig1).

Archetypes were grouped into normal (AT 5), peripheral (AT 2, 3, 6, 9), paracentral (AT 4, 7), and (A8) generalized defect classes. One standard deviation (SD) increase in POAG PRS was associated with 2.22-times higher odds of paracentral loss (95% CI 1.75-2.83, p<0.001) and 1.67-times higher odds of peripheral loss (95% CI 1.46-1.94, p<0.001) compared to normal AT. A 1-SD increase in NTG PRS was associated with 3.02-times higher odds of paracentral loss (95% CI 1.31-6.93, p=0.009), 1.89-times higher odds of peripheral loss (95% CI 1.12-3.08, p=0.016), and 0.32-times lower odds of generalized loss (95% CI 0.14-0.75 p=0.009) compared to normal AT. A 1-SD increase in HTG GRS was associated with 2.05-times higher odds of a generalized loss (95% CI 1.22-3.45, p=0.007) compared to normal AT. POAG PRS and NTG PRS were not significantly associated with generalized loss.

Conclusions : Patients with higher POAG PRS are more likely to have peripheral loss while those with higher NTG PRS are more likely to have paracentral loss and those with higher HTG genetic risk were most likely to have diffuse loss; these findings have important implications for disease prognostication.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Fig1