Genetics play an evolving role in glaucoma screening and management with polygenic risk scores serving as a way to enhance early diagnosis and treatment.
A new study reviewed the progress in glaucoma genetics over the past 25 years, starting with the identification of MYOC and CYP1B1 as key genes. Researchers also named genes associated with exfoliation glaucoma and genes associated with primary open-angle glaucoma (POAG) in more recent discoveries.
“Identifying additional glaucoma genes forced a change from thinking of glaucoma as solely a monogenic disease caused by a single gene mutation with a major effect to realizing most forms of glaucoma are polygenic,” researchers wrote in their findings published in The Journal of Glaucoma.
Polygenic risk scores (PRS) are being refined to improve their clinical utility in predicting glaucoma risk, though they need to be validated across diverse ethnic populations, particularly those who are at higher risk of POAG. “Africans have a higher clinical risk of POAG, but paradoxically, fewer of these individuals have been included in glaucoma genetics research,” the researchers noted. Current PRS models are predominantly based on Northern European populations, which may limit their applicability to other ethnic groups.
With more genome-wide associate studies, PRS could stratify individuals based on their genetic risk, allowing for more focused and efficient screening strategies especially with varied guidelines across countries. PRS may also be able to help effectively triage patients in outpatient clinics who are more likely to develop glaucoma, inform the significance of incidental findings in genetic testing, and impact glaucoma surveillance with population-wide testing.
The expanding capability and availability of genetic testing necessitates further research to determine when and how to act on specific genetic results, such as when infants are found to be at high risk of developing adult-onset POAG.
“If we over-treat someone with a spurious genetic result, this may cause harm from treatment. If we falsely reassure someone that they do not have a specific genetic risk when they may have other genetic risk factors, they could miss being diagnosed,” the researchers said. They also raised questions of appropriate treatments (such as selective laser trabeculoplasty when finding mild signs of glaucoma, or oral niacin to protect the optic nerve) in patients who are at higher risk because of genetic findings.
While genetics offers promising tools for glaucoma screening and management, ongoing research is necessary to ensure these tools are accurate, equitable, and applicable across diverse populations.
A full list of author disclosures can be found in the published research
