Primary Open Angle Glaucoma Polygenic Risk Score is Associated with Disease Progression

Area of Science:

• Ophthalmology
• Genetics
• Medical Research

Background:

• Open-angle glaucoma (OAG) is a leading cause of irreversible blindness.
• Predicting disease progression and treatment burden in OAG remains a clinical challenge.
• Polygenic risk scores (PRS) are emerging tools for assessing genetic predisposition to complex diseases.

Purpose of the Study:

• To investigate the association between a polygenic risk score (PRS) for primary open-angle glaucoma (POAG) and the progression of open-angle glaucoma (OAG).
• To evaluate the relationship between POAG PRS and the treatment burden in patients with OAG.
• To assess the utility of PRS in a multi-ancestry population for glaucoma prognostication.

Main Methods:

• A longitudinal cohort study included 950 individuals with OAG from two biobank cohorts.
• A POAG PRS was developed using cross-ancestry genome-wide association study data.
• Associations between PRS and visual field (VF) progression (mean deviation slope) and treatment burden (medications, laser, surgery) were analyzed using logistic and Cox regression models.

Main Results:

• Each standard deviation (SD) increase in PRS was associated with a faster rate of VF decline (β = -0.02 dB/year per SD; P = 0.007).
• Higher PRS correlated with increased odds of OAG progression (OR = 1.22 per SD; P = 0.014) and greater treatment burden (OR = 1.47 per SD; P < 0.001).
• In one cohort, higher PRS predicted shorter time to glaucoma procedures, even in early-stage disease.

Conclusions:

• Elevated POAG PRS is significantly associated with accelerated VF progression and higher treatment intensity in OAG patients.
• These findings suggest that PRS can be a valuable tool for predicting glaucoma disease trajectory.
• Genetic risk stratification holds potential for personalized management strategies in OAG.