Through a painstaking teasing-apart of complex relationships, Associate Professor Kathryn Burdon and colleagues are aiming to build a comprehensive picture of the connections between genetics and eye disease.
Working with colleagues at the University of Tasmania's Menzies Institute for Medical Research, she is trying to disentangle the role that genes play in the development of three eye diseases, in particular – glaucoma, keratoconus and diabetic retinopathy.
Associate Professor Burdon and collaborators from Flinders University last year published research in Nature Genetics in which they identified the gene variations that play a part in the development of primary open angle glaucoma – a type of glaucoma which causes rapid blindness.
Glaucoma is the progressive loss of vision, starting with peripheral vision, caused by damage to the optic nerve.
"The research for this paper compared the genomes of 1155 people with severe glaucoma to several thousand people without glaucoma at 7.5 million sites on the genome. We discovered that genetic variation near three genes – AFAP1, ABCA1 and GMDS – increases the risk of severe glaucoma," Associate Professor Burdon said. "We have found variation in these genes, but as yet we don't know the mechanism causing the disease, so we are looking to see if those variants can be associated with some other clinical measure – for example, the rate of vision loss or the eye pressure."
If we can say these patients are at high risk … we can treat their eye pressure early and aggressively and prevent their blindness
The project is now based at Flinders University but originated at Menzies in the 1990s, when Professor David Mackey started the Glaucoma Inheritance Study in Tasmania. This database of several thousand related people with glaucoma was the cornerstone of the Nature Genetics paper, although it was significantly built upon in the next decade with the addition of hundreds more unrelated participants from throughout Australia.
Glaucoma is preventable if discovered early and treated aggressively. Associate Professor Burdon and Menzies colleague Dr Alex Hewitt are recruiting for a study of patients who don't yet have glaucoma but who have eye irregularities which may lead to it. Knowing which gene variations to test for will allow practitioners to more accurately balance risk, decreasing the amount of unnecessary preventative treatment that may have side effects and freeing up practitioners to work on people who are more likely to develop the illness.
"It's never going to be perfect based on the genetics, but if we can say these patients are at high risk because of their genes, and they have some early symptoms, then we can treat their eye pressure early and aggressively and prevent their blindness," Associate Professor Burdon said. "Patients at low genetic risk, whose symptoms are not progressing, can be monitored less intensively."
She said we were still five to 10 years from having a comprehensive genetic picture to help guide the prevention of glaucoma but specialists are bringing genetic testing into management of eye disease.
"We are seeing a rapid response in those people," she said. "If they are not treated they go blind really quickly, and once that happens there's nothing we can do. If we can get in early before vision is lost, we can prevent vision loss in a large proportion of cases."
Associate Professor Burdon's research is funded by the National Health and Medical Research Council and Glaucoma Australia (through the Ophthalmic Research Institute of Australia).