Two abstracts presented at ARVO evaluated the utility of polygenic risk scores (PRS) in the identification of primary open-angle glaucoma risk. While both studies confirmed the advantages of using PRSs, one specifically showed that early treatment reduced the risk of disease onset in those with a higher genetic risk, suggesting interventions in these patients should be prioritized.

Two abstracts presented at ARVO evaluated the utility of polygenic risk scores (PRS) in the identification of primary open-angle glaucoma risk. While both studies confirmed the advantages of using PRSs, one specifically showed that early treatment reduced the risk of disease onset in those with a higher genetic risk, suggesting interventions in these patients should be prioritized. Photo: Sarah B. Klein, OD. Click image to enlarge.

Hundreds of common genetic variants for primary open-angle glaucoma (POAG) have been discovered and various groups have devised methods to calculate a polygenic risk score (PRS) in hopes of finding a future clinical application of genomics in glaucoma care. In two papers presented at ARVO this past Sunday, the utility of polygenic risk scores in POAG were examined and provide further evidence of their potential value in detection. Though neither method is currently available to doctors for use, these studies show encouraging results that boost confidence in this becoming a future clinical technique one day.

The first study, aimed at identifying individuals who are at low risk of disease onset, included 1,010 participants (2,018 eyes) from the Ocular Hypertension Treatment Study (OHTS) with genotype data available.1 Eyes with high eye pressure were categorized into three disease onset risk groups using baseline OHTS model of age, IOP, vertical cup-to-disc ratio, central corneal thickness, and pattern standard deviation. When the model was adjusted for these variables and randomization status, the glaucoma PRS low risk threshold (48th percentile) was associated with a 2.15-fold likelihood of remaining disease-free at 20 years.

Those who were randomized for early treatment and below the threshold had conversion rates of 3.5% at 10 years and 13.2% at 15 years. Those above the threshold had rates of 7.6% at 10 years and 30.1% at 15 years. Similar trends were noted in the observation group, with below-threshold individuals converting 9.3% at 10 years and 29.4% at 15 years, while those above had rates of 18.8% at 10 years and 45% at 15 years.

The authors concluded that a PRS can identify those at lower risk for POAG onset. “The results showed that those with a lower genetic risk score had a significantly lower chance of developing glaucoma, especially among those initially considered at high risk,” they wrote. “Early treatment reduced the risk for those with a high genetic risk but had less impact on those with a low genetic risk. This suggests the genetic risk score could help identify patients who might benefit most from early treatment to prevent glaucoma.”

The second study examined whether or not recalling patients based on their PRS would aid in POAG diagnosis.2 It included genotype data from over 400,000 UK Biobank participants, including 14,171 POAG cases. PRS was computed for >54,000 individuals in Mount Sinai BioMe and >45,000 in the Mass General Brigham Biobank. Researchers invited individuals between the ages of 35 and 90 in the top and bottom PRS categories to have a comprehensive eye exam.

The final 201 subjects had a mean age of 66.2 ± 9.6 years and 58.2% were women. Clinical evidence of POAG was found in 35.9% of subjects in the top PRS category and 4.2% in the bottom one. Seventy-five percent of patients had reliable VF tests, among which the average mean deviation in the top vs. bottom PRS deciles were -2.26 ± 3.90 dB vs. -0.89 ± 1.96 dB. Overall, the odds ratio for POAG in the high vs. low PRS groups was 12.7.

In summary, both studies show that PRS to be a valuable tool in identifying those at risk of developing POAG, which can aid in treatment intervention, and further studies are ongoing.

Original abstract content ©2024 Association for Research in Vision and Ophthalmology.

1. Zebardast N, Sekimitsu S, Aziz K, et al. Primary open angle glaucoma polygenic risk score can identify individuals at low risk of disease onset in the Ocular Hypertension Treatment Study. ARVO 2024 annual meeting.

2. Zhao H, Pasquale LR, Zebardast N, et al. Screening by glaucoma polygenic risk score to identify primary open-angle glaucoma in two biobanks: an interim report. ARVO 2024 annual meeting.