Genetic Risk Linked to Rapid Visual Field Worsening in Glaucoma

According to a report in JAMA Ophthalmology, individuals with a high polygenic risk were found to be at an increased risk of rapid structural and functional progression in early-stage glaucoma, despite receiving intensive treatment.

“Polygenic risk scores (PRSs) are a probabilistic summary of an individual’s genetic risk of a disease or trait and are increasingly recognized as a tool in disease risk prediction and phenotyping,” Owen M. Siggs, MD, DPhil, of the department of ophthalmology at Flinders University in Australia, and colleagues wrote. “In the context of glaucoma, PRSs have been shown to effectively stratify risk of glaucoma, age at diagnosis and the rate of OCT thinning in early manifest glaucoma cases.”

The researchers collected data from 1,103 people with primary open-angle glaucoma (POAG) to examine the association of polygenic risk with visual field progression in early-stage glaucoma.

The study included 1,777 eyes from 896 individuals for structural progression analyses and 1,563 eyes from 808 individuals for functional progression analyses. The participants, who were mostly of European ancestry, had a mean age of 62.1 years, and 44% were men. Additionally, they were matched with 17,642 individuals for PRS reference.

The results showed that individuals in the top 5% PRS risk group were at a greater risk of visual field progression compared to the bottom 95% PRS group after 5 years (HR = 1.5; P = .005) and had a faster rate of peripapillary retinal nerve fiber layer (pRNFL) thinning (mean = –1.64 vs. –1.36; P = .01), after adjusting for age, sex and OCT device.

Despite receiving higher treatment intensity, participants in the top 5% PRS group were still more likely to experience fast pRNFL progression compared to the bottom 95% PRS group (OR = 1.5; P = .02).

On the other hand, individuals in the bottom 20% PRS risk group were found to be at a lower risk for visual field progression compared to an intermediate 75% risk group over 3 years (HR = 0.52; P = .04). They also had a slower rate of pRNFL progression by 0.27 m per year (P = .04).

“Both structural and functional glaucoma progression outcomes were influenced by glaucoma genetic risk, with individuals in the top 5% of the PRS distribution progressing earlier than those in the bottom 95%, corresponding with a higher treatment intensity in the former,” Siggs and colleagues wrote.

“Since treatment is initiated or escalated in response to glaucoma worsening and is highly effective at slowing progression, we would expect the true association of PRS with glaucoma progression to be even greater and would also anticipate a similar association between PRS and time to treatment initiation or escalation.”