Diabetic eye disease: Laying the foundations for new treatments

Professor Chandra Balaratnasingam’s MDFA-funded research is exploring the cellular changes that occur in diabetic macular ischaemia (DMI) to help develop a breakthrough therapy.

About 1.7 million Australians are living with diabetes, including 500,000 who haven’t been diagnosed.

Everyone with diabetes is at risk of diabetic eye disease, such as diabetic macular ischaemia (DMI).

However, there is currently no treatment for DMI — partly due to our limited understanding of the cellular pathways that are activated in DMI. That’s why Macular Disease Foundation Australia has awarded an MDFA Research Grant to Professor Chandra Balaratnasingam, who hopes to lay the groundwork for new treatments for this common cause of irreversible vision loss.

“The aim of this study is to try and understand the changes to the cells in the retina that are associated with the formation of ischaemia,” Prof Balaratnasingam says.

“It’s very simple: ischaemia is the eye not getting enough blood and therefore not enough oxygen. So if we can understand the changes to the cells that precede this, then we can find new, targeted treatments to prevent it from happening.”

We already have an effective treatment for diabetic macular oedema (DMO) in the form of intravitreal injections, also known as eye injections or IVI.

DMO occurs when the damaged blood vessels leak fluid and cause swelling of the macula, the area of the retina responsible for detailed central vision.

But we don’t have any way to treat diabetic macular ischaemia (DMI), which is a reduction in the blood supply to the retina.

In his MDFA-funded project, Prof Balaratnasingam is using donor tissue from patients with diabetes to expand our knowledge of how the cells change when DMI develops.

It’s hoped these insights will then lead to the development of new drugs that target these cellular changes, giving us a new therapy to prevent vision loss or reverse vision loss once it’s occurred.

“Diabetic eye disease is the most common cause of blindness in working-age people in Australia. It will be nice to get a treatment for DMI, to augment all the other treatments we have for diabetes,” Prof Balaratnasingam says.

The goal is really to identify new targets for therapies. If you know the specific cell types that change, then we can develop very nuanced therapy to target those changes.

Prof Balaratnasingam imagines treatment would look similar to eye injections for DMO, just using a different drug with a different target.

As a retinal specialist at Perth’s Lions Eye Institute, Prof Balaratnasingam often performs surgeries — such as a vitrectomy — on people with diabetic eye diseases like DMI.

But finding a new way to treat the eye before complications develop would reduce the number of people who end up needing these serious operations.

I operate on a lot of people with diabetic retinal complications, and sometimes the surgeries can take three or four hours and the outcomes are highly variable.

Prof Balaratnasingam

“We try and avoid surgery, if we can, and we probably can do a lot better in managing these patients than we currently are.

“To find a cure is quite difficult. But if we can at least find some way of minimising the development of ischaemia, I think that’s a huge first step.

“If we can actually treat the eye early, I think we can really make a huge impact in terms of quality of life for the patients.”

Prof Balaratnasingam explains that diabetes is very common in Australia, and its prevalence is only expected to increase.

Although diabetic eye disease has many risk factors — including genetics and lifestyle — the longer you have diabetes, the more likely you are to develop complications of the eye.

With the risk of vision loss to diabetes on the rise, Prof Balaratnasingam’s research has great potential to improve the wellbeing of a growing number of people, by helping to develop a new sight-saving treatment.

“If we can maintain excellent vision, the benefits are pretty widespread: you improve the patient’s quality of life, they can work longer, they’re happier.

“Vision has multiple levels of benefits in terms of reducing morbidity from other illnesses and diabetes … there will be so many benefits.

“If we can reduce or prevent ischaemia, and we give them good vision, it will have a profound benefit to their life overall.”

While Prof Balaratnasingam has published over 100 peer-reviewed manuscripts and his work has been editorialised in major international journals, he admits that securing research funding remains “extremely difficult”.

The pool of funds allocated to medical research is limited and highly competitive, especially for eye diseases compared to more high-profile conditions.

MDFA launched its Research Grants Program in 2011 to provide a dedicated source of research funding for macular disease in Australia, with the ultimate aim of finding discoveries that save people’s sight.

And Prof Balaratnasingam has a message for MDFA’s generous donors who are making this project possible.

A big thank you, I’m really very grateful to be given the funding and the opportunity to pursue this line of research.

“I’m really pleased and excited that the donors saw value in what we’ve proposed with this project. It has real capacity to translate into clinical application to improve people’s wellbeing, so we’re obviously very grateful for the donors for their support and funding.”