SA Pathology Leads Worldwide Panel Helping Stop Glaucoma in its Tracks

15 June 2022

Dr Andrew Dubowsky is section head of the Genetics and Molecular Pathology laboratory at Flinders Medical Centre and also co-Chair of a Curation Expert Panel that could change millions of lives. 

Primary Open Angle Glaucoma (POAG) affects 50 to 60 million people worldwide and is the most inheritable form of blindness. Andrew aims to help clinicians identify disease causing changes within genes of young individuals who are yet to be affected, intervening before currently available treatments cease to be an effective option.

The journey began in 2007 when Professor Jamie Craig, a Consultant Ophthalmologist at the Flinders Medical Centre sought to translate into the clinic his pioneering research findings investigating the association between the disease and a gene called Myocilin.

The catch – there was no formal diagnostic genetic testing available through a NATA accredited laboratory. Andrew was new to SA Pathology and eager to be involved with the study, and soon a testing partnership was formed.

From there, the research identified more genes and different associations. Testing continued to expand too. Interpretation of the testing went directly through Andrew and his team, and with it, their interest in Glaucoma and Myocilin increased.

Not long after, Jamie and Andrew combined with Emmanuelle Souzeau, a genetic counsellor, and the three decided to dedicate themselves to help diagnose the disease.

In 2015, the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology released guidelines to make interpretation of genetic variants more consistent. This call out, along with easy access to Clin-Var, an open-access database, set the team on the path they find themselves on today.

“I said to Emmanuelle, we’ve been doing this for a while, and we’re pretty well the only ones in Australia looking at specific single-gene testing. What about we try to get this started and then try to get others throughout the world involved?” 

Creating a worldwide range of experts in different fields was no small feat, so the duo turned to Jamie once again to get the ball rolling.

The committee started in 2019 and has continued to expand.

Over the last two years they have finished constructing the gene specific rule set, which have been peer-reviewed. They have piloted over 70 variants too, which are already accessible within Clin-Var, holding the status of a Food and Drug Administration recognised database.

The expert panel is now travelling through the remainder of the variants and reviewing them. 

“When someone has glaucoma or appears to have some family history, they can be tested and then our classifications can be used to help the individual because they will know what they’ve got, and why they’ve got glaucoma. While they won’t get their sight back, they can make decisions for their family.” 

Ultimately, Andrew and the team are providing people with answers and options.

“If their young child has the same variant they carry, they’ll know what the classification is. If it’s benign, we don’t have to worry, but if not, they can inform their children, make decisions, have better management of glaucoma and slow down or potentially eliminate the possibility of them also going blind.”

The panel is now looking at moving on to Primary Congenital Glaucoma, but with every set of rules they create, the goal is simple, “to provide classifications or the ability to classify variants in these genes to be used in the clinical management of patients."

Congenital Glaucoma can often go undiagnosed as parents are carriers and it's a recessive disorder. Andrew has encountered families who have used knowledge to make informed reproductive choices.

“These are big decisions. And making these sorts of very big decisions requires confidence in being able to understand what we’ve found and how well a clinician can make a decision based on what we’ve published.”

Congratulations to Andrew and the team for the positive impact you’re having on lives around the globe.