In Glaucoma, Polygenic Risk Score Can Predict Structural, Functional Progression

High polygenic risk scores (PRS) for glaucoma are associated with more rapid disease progression in early primary open-angle glaucoma (POAG), despite more intensive treatment, according to findings published in JAMA Ophthalmology.

Data for this study were sourced from the Progression Risk of Glaucoma: Relevant SNPs With Significant Association (PROGRESSA) and QSkin studies. The included patients had POAG, were evaluated for glaucoma PRS, and their PRS was compared with structural and functional disease progression. A cohort of 17,642 individuals was used to define the ancestrally-matched normative distribution.

A total of 896 individuals were included in the analysis of structural progression and 808 in the analysis of functional progression. The study population comprised individuals aged mean 62.1 (standard deviation [SD], 9.9) years, 44% were men, and 98.5% had self-reported European ancestry.

A total of 11.97% of the study cohort had a PRS in the top 5% of the normative distribution. Compared with the bottom 95%, more of the patients in the top 5% had a family history of glaucoma (56.1% vs 37.2%; P <.001) and used more antiglaucoma drops (mean, 1.57 vs 1.15; P <.001), respectively.

At baseline, mean visual field mean deviation did not differ on the basis of PRS (mean difference [MD], -0.4 dB; P =.10). However, having a PRS in the top 5% is associated with visual field worsening at follow-up compared with the bottom 95% (hazard ratio [HR], 1.5; 95% CI, 1.13-1.97; P =.005).

More of the top 5% cohort had fast peripapillary retinal nerve fiber layer (pRNFL) progression (> 1μm/year; 47.6% vs 39.6%; P =.02) and a faster pRNFL rate of thinning (mean, -1.64 vs -1.36 μm/year; P =.01) compared with the bottom 95%, respectively. Similar to visual field progression, having a PRS in the top 5% associated with fast pRNFL progression compared with the bottom 95% (odds ratio [OR], 1.5; 95% CI, 1.1-2.2; P =.02).

The subset of individuals who had a PRS score in the bottom 20% of the normative distribution (n=72) associated with slower visual field worsening at three years (HR, 0.52; 95% CI, 0.28-0.96; P =.04) and slower rate of pRNFL progression (MD, 0.27 μm/year; P =.04) compared with the intermediate 75% group.

This study may have been limited by not having a non-glaucoma control cohort.

“Those in a high PRS group may deserve particular attention: despite more intensive treatment, these individuals remained more susceptible to progression and may therefore benefit from more intensive treatment including a lower-target IOP,” the researchers report.

Disclosure: Multiple authors declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.