Sight and insight: unlocking treatment and knowledge for inherited retinal diseases

Inherited Retinal Diseases (IRDs) are the leading cause of blindness among working-age Australians, and until recently were considered untreatable.

Inherited retinal diseases are a group of genetic disorders that affect the retina, the light-sensitive tissue at the back of the eye. These conditions are characterised by progressive degeneration of retinal cells, including rod and cone photoreceptor cells, leading to vision loss.

Inherited retinal diseases are caused by changes in specific genes that are passed down through families. These changes – like DNA spelling mistakes – affect how proteins in our body function, including those in our eyes. So far, we know of more than 300 genes that are associated with inherited retinal diseases.

Department of Optometry and Vision Sciences researcher Dr Ceecee Britten-Jones says most people with inherited retinal diseases experience their first symptoms in late adolescence or early adulthood.

"The first symptoms may not be immediately obvious and many inherited retinal diseases are first picked up by an optometrist during a routine eye exam. The clinician might observe signs of early changes in the back of the eye or notice symptoms that warrant further investigation."

She says common symptoms of inherited retinal diseases include:

• Difficulty seeing in dim or dark environments
• Reduced peripheral vision, leading to frequent collisions with objects or people
• Increased glare and sensitivity to bright lights
• Diminished central vision, making it challenging to read, recognise faces, or watch television
• Difficulty perceiving certain colours or distinguishing between them.

"Over the course of years or decades, these symptoms usually worsen, leading to gradual vision loss. Receiving an inherited retinal disease diagnosis can be devastating, as vision loss or blindness is ranked as one of the most feared health conditions."

Some inherited retinal diseases only affect vision, while syndromic types can also affect other body systems, including hearing loss and kidney disease.

"The onset age of the disease can influence its management. For infants with severe vision issues, additional challenges like delays in speech and social skills may occur," Dr Britten-Jones says. "Support in the form of low vision aids, educational resources, and counselling becomes crucial."

Advances in genetic testing have expanded the ability to understand and diagnose inherited retinal diseases. By identifying the exact genetic changes responsible for these conditions, clinicians can provide more accurate diagnoses and offer relevant genetic counselling for affected families. Genetic testing is also important for accessing new treatments and benefiting from the latest advancements.

"In 2017, the world’s first ocular gene therapy treatment was approved by the United States' Food and Drug Administration (FDA) for an inherited retinal disease. This treatment targets the condition caused by changes in the RPE65 gene. Since this first ocular gene therapy was approved, more than 30 additional gene therapies are currently in development, offering renewed hope to patients.

"Gene therapy involves injecting a functional copy of the gene in the eye, enabling retinal cells to produce the RPE65 protein, which helps maintain the visual cycle and convert light into electrical signals for the brain to process. To know what gene to target with therapy, an accurate genetic diagnosis is crucial."

The VENTURE team, a collaboration between the University of Melbourne and Centre for Eye Research Australia, are trying to learn more about IRDs using advanced genetic analysis. The team does this by collecting images of the back of the eye, combined with genetic information, to expand their insights into different IRDs and the genes that cause them. They collaborate with researchers from all around the world to diagnose new cases and develop new treatments.

"Using advanced genetic analysis, the VENTURE team has been able to diagnose many people who are losing their vision," Dr Britten-Jones says.

"While a diagnosis may not equal a cure, knowing the exact cause of disease can help those affected feel more informed, so they can make decisions about their own future.

"Every eye scan and genetic test result contributes to a larger and clearer picture of these rare inherited retinal diseases and as our registry grows, we can see common features and distinct patterns emerge."

In addition to more treatment options, some IRD patients may be eligible for clinical trials.

"Each trial has specific eligibility criteria. Our VENTURE team works closely with clinical trials teams at Cerulea Clinical Trials to bring new treatments to Australia, and interested individuals can contact our team on IRD@groups.unimelb.edu.au to learn about the registry and be notified about relevant trials. Additionally, patients should discuss their options with their specialists, such as ophthalmologists, visit research institution websites to find current trials, or contact patient advocacy groups such as Retina Australia for further information.

"It is our goal for this this research to lead to new, exciting treatments that may brighten the darkness of families with inherited retinal diseases."

The VENTURE project is a collaborative effort driven by researchers at the University of Melbourne and Centre for Eye Research Australia. This work, highlighted in the Reel Impact video, has received invaluable contributions from Associate Professor Lauren Ayton, Dr Tom Edwards, Dr Ceecee Britten-Jones, Ms Janise Hermawan, Mr Parker Truong, Ms Sujani Thrimawithana, Ms Elise Cichello, Dr Sena Gocuk, and the Vision Optimisation/Retinal Gene Therapy research teams.