ArticleOphthalmology2025
Genetic Risk for Open-Angle Glaucoma Subtypes Is Associated with Specific Visual Field Defect Classes.
Article in Ophthalmology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeWe investigated visual field (VF) archetype-genotype associations for open-angle glaucoma (OAG) and its subtypes, high-tension glaucoma (HTG) and normal-tension glaucoma (NTG).
designCross-sectional, population-based study.
participantsA total of 79 357 VF results from 11 572 patients with OAG at Massachusetts Eye and Ear (2012-2022) were used to identify VF archetypes. Archetype-genotype correlations were performed on participants with genotyping data, VF results, and OAG codes (H40.1x) from the Mass General Brigham Biobank, and 3 Health Professional Cohorts (n = 1517) with primary open-angle glaucoma (POAG) and reproducible VF loss.
methodsPrimary open-angle glaucoma polygenic risk score (PRS), NTG PRS, and weighted HTG genetic risk score (GRS) from genome-wide association studies were calculated for 1517 participants (2408 eyes). Logistic regression assessed VF archetype-genotype associations.
main outcome measuresAssociations between PRS or GRS and VF archetypes.
resultsNine archetypes were identified, including normal and various paracentral, peripheral, and total loss patterns. In a logistic regression model adjusted for age, sex, and ancestry, a 1-standard deviation (SD) increase in POAG PRS was linked to 1.65-times higher odds of paracentral defects (adjusted odds ratio [aOR], 1.65; 95% confidence interval [CI], 1.32-2.08) and 1.30-times higher odds of peripheral defects (aOR, 1.3; 95% CI, 1.14-1.48). A 1-SD increase in NTG PRS was associated with 1.69-times higher odds of paracentral defects (aOR, 1.69; 95% CI, 1.23-2.3) and 1.28-times higher odds of peripheral defects (aOR, 1.28; 95% CI, 1.06-1.54). A 1-SD increase in HTG GRS was linked to 0.68-times lower odds of both paracentral defects (aOR, 0.68; 95% CI, 0.57-0.82) and peripheral defects (aOR, 0.68; 95% CI, 0.62-0.76). A 1-SD increase in HTG GRS also was associated with 1.31-times higher odds of total loss (OR, 1.31; 95% CI, 1.01-1.77) in an unadjusted model, but was not significant in the adjusted model.
conclusionsHigher POAG PRSs and NTG PRSs were associated with paracentral VF loss, whereas higher HTG GRS was linked to total VF loss, but not paracentral defects. Genetic risk for glaucoma subtypes is associated with specific VF defects, which may affect disease diagnosis and prognostication. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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