Glaucoma Prediction Improved by New Genetic Test

Glaucoma is a group of eye diseases that can cause vision loss and blindness by damaging a nerve in the back of the eye called the optic nerve. It is the second leading cause of blindness worldwide and can be difficult to predict and diagnose. Researchers are looking for new ways to predict glaucoma before onset. A new study by Flinders University, the QIMR Berghofer Medical Research Institute, and other collaborators reveals a new genetic test for glaucoma. The researchers say the test has the ability to identify 15 times more people at high risk of glaucoma than an existing genetic test.

Their findings are published in the journal JAMA Ophthalmology in a paper titled, “Association of Monogenic and Polygenic Risk With the Prevalence of Open-Angle Glaucoma.”

“Early diagnosis of glaucoma can lead to vision-saving treatment, and genetic information can potentially give us an edge in making early diagnoses, and better treatment decisions,” said lead researcher associate professor Owen Siggs, PhD, from Flinders University in South Australia and the Garvan Institute of Medical Research in Sydney, NSW.

Senior author, Flinders University professor Jamie Craig, PhD, said the latest research highlights the potential of the test in glaucoma screening and management.

“Genetic testing is not currently a routine part of glaucoma diagnosis and care, but this test has the potential to change that. We’re now in a strong position to start testing this in clinical trials,” said Craig, a consulting ophthalmologist who also runs a world-leading glaucoma research program at Flinders University, funded by Australia’s NHMRC.

Clinical and genetic data were obtained for 2,507 individuals from the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) and 411,337 individuals in cross-sectional cohort studies including individuals of European ancestry in the UK Biobank.

The new test, performed on a blood or saliva sample, has the potential to identify high-risk individuals before irreversible vision loss occurs.

“Individuals at high polygenic risk, defined as those in the top 5% of an unselected population, had a glaucoma risk (odds ratio [OR], 2.77; 95% CI, 2.58-2.98) comparable with the risk among individuals heterozygous for the MYOC p.Gln368Ter variant (OR 4.19; 95% CI, 3.25-5.31), which is the most common single-gene variant known to cause primary open-angle glaucoma,” wrote the researchers.

“High polygenic risk was more than six times more common than MYOC p.Gln368Ter heterozygosity in ANZRAG (15.7% vs 2.6%) and more than 15 times more common in the general population (5.0% vs 0.32%). Within ANZRAG, high polygenic risk was associated with a mean (SD) age at glaucoma diagnosis that did not differ from the age at glaucoma diagnosis among individuals heterozygous for MYOC p.Gln368Ter (57.2 [14.2] vs 54.8 [13.6] years; P > .99).”

The research team is looking to launch a spin-out company to develop an accredited test for use in clinical trials, with recruitment expected to begin in 2022.