A new genetic test developed by researchers at QIMR Berghofer and Flinders University, along with international collaborators, can identify people at up to ten times the normal risk of developing open-angle glaucoma, the most common form of the disease and the leading cause of irreversible blindness worldwide.
The findings, published today in Ophthalmology, show the test is a major improvement on earlier versions and could help doctors detect and treat glaucoma before sight is lost.
Glaucoma damages the optic nerve and usually has no symptoms in its early stages. About half of all people with glaucoma remain undiagnosed, even in countries with good access to eye care. Because vision loss cannot be restored, early detection is critical.
The test uses a polygenic risk score, which combines the effects of millions of genetic variations into a single measure of a person's inherited risk. Researchers built the new score using genetic data from more than six million people, including almost 300,000 people with glaucoma. The previous version, published in 2020, was based on about 8,000 glaucoma cases.
Lead researcher Professor Stuart MacGregor, Head of QIMR Berghofer's Statistical Genetics Laboratory, said the much larger dataset had delivered a significant leap in predictive accuracy.
"In Australians of European ancestry, people in the highest 10 per cent of genetic risk were ten times more likely to have glaucoma than everyone else. Our earlier test identified about a four-fold increase in risk," Professor MacGregor said.
"To our knowledge, this is the strongest genetic risk prediction reported for any common complex disease." The study found people in the highest 10 per cent of genetic risk developed glaucoma about 25 years earlier, on average, than those
in the lowest 10 per cent. A healthy 65-year-old of European ancestry in the highest 20 per cent of genetic risk has an estimated 10 per cent chance of developing glaucoma within the next decade, compared with just 0.4 per cent for someone in the lowest 20 per cent.
The score also helped predict disease severity. In a long-term study of people with suspected or early glaucoma, 24 per cent of those in the highest-risk group required glaucoma surgery by age 80, compared with none in the lowest-risk group. The test also identified patients more likely to require intensified treatment, have affected family members, and added substantial predictive value beyond eye pressure measurements, the most commonly assessed glaucoma risk factor.
Professor MacGregor said the test could help clinicians determine who would benefit from closer monitoring and earlier treatment, while reducing unnecessary testing for those at lower risk.
"Glaucoma is very treatable if it is caught early, but many people are diagnosed only after permanent damage has occurred. A test like this can help direct eye care resources to the people who need them most," he said.
Professor Jamie Craig, from Flinders University, said the research highlighted the potential for more personalised glaucoma care.
"This research has opened the door to a personalised approach to glaucoma risk analysis for the population, family members of patients, and those already showing signs of early stage disease. It will allow us to get the timing of treatments right to prevent vision loss," Professor Craig said.
The researchers tested the score across people of European, African, East Asian, South Asian and Hispanic ancestry. While it
identified higher-risk groups in all populations, performance was strongest in people of European ancestry, reflecting the greater availability of large genetic datasets from those populations.
"Most of the large genetic datasets available today come from people of European ancestry. Improving accuracy for all populations is an important priority for our next phase of work," Professor MacGregor said.
The researchers say further studies are needed to assess the cost-effectiveness of incorporating the test into targeted glaucoma screening programs.
Disclosure statement:
Professor Stuart MacGregor, Professor Jamie Craig, Associate Professor Alex Hewitt and Professor Owen Siggs are co-founders of Seonix Bio, the entity that offers the testing service. Professor MacGregor, Professor Jamie Craig, Dr Nick Haan and other study authors hold financial interests in the company. Dr Mathias Seviiri and Dr Guiyan Ni are employees of Seonix Bio. Two co-authors are employees of and hold stock in 23andMe. QIMR Berghofer holds a licensing interest related to intellectual property used by Seonix Bio. All relevant interests are disclosed in the published paper and were managed in accordance with institutional conflict of interest and commercialisation policies.