Longer-acting eye treatment could reduce vision loss for Indigenous Australians
Indigenous people in Australia experience three times more vision loss than non-indigenous people, creating a worrying gap in vision.
This is largely due to diabetic macular edema (DME). Here, the blood vessels at the back of the eye (the retina) are damaged by high blood sugar. Over time, this causes swelling (oedema) of the central part of the retina (the macula).
Macular edema blurs central vision, impairing the ability to recognize people’s faces, drive and work, and perform other essential tasks. DMO affects around 23,000 Indigenous people in Australia, most of whom are of working age. Similar trends are reported in other developed states with indigenous populations, including New Zealand, Canada, and the United States.
The good news is that BMD can be treated, with drugs called anti-VEGF agents. We have undertaken a world-first clinical trial to test a longer-acting BMD treatment for Indigenous Australians. In doing so, we have also learned to undertake culturally sensitive research about the country.
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A longer lasting treatment
When injected into the eye by an ophthalmologist (eye surgeon), anti-VEGF drugs are safe and effective for treating DME. The injections do not hurt, since the eye is anesthetized. The catch is that anti-VEGF agents have a relatively short duration of action, requiring them to be re-administered as often as monthly.
Many Aboriginal patients find it impractical, for a variety of complex reasons, to attend ten to twelve eye appointments per year. So there is a need for an alternative.
Longer acting drugs exist. An example is an implant of dexamethasone (commercially known as Ozurdex(R)), a steroid injected into the eye. The dexamethasone implant only needs to be dosed every three months.
The dexamethasone implant is PBS-approved for BMD in Australia, but has never been evaluated in an aboriginal population. This is important because a possible side effect of steroid medications is increased pressure in the eye. If left untreated, it can lead to a condition called steroid-induced glaucoma.
Glaucoma is thought to occur less frequently in Aboriginal people, suggesting differences in eye pressure physiology between Caucasian and Aboriginal eyes. In addition, the incidence of steroid-induced glaucoma subtype has never been studied in Aboriginal people. This is especially important for people living in remote areas, as glaucoma is a ‘silent disease’, requiring regular check-ups for detection and treatment.
Historical barriers preventing this type of research include cultural and geographic factors, as well as a lack of endorsement from Indigenous health services and “staff champions”.
Not only what to look for, but how
At Lions Eye Institute, we sought to overcome these barriers with the OASIS Study – a world-first clinical trial in ophthalmology to exclusively recruit Indigenous patients.
We framed our study around ten key success factors, including support from all participating Indigenous medical services, free and safe treatment, free transportation, appointment reminders, and cultural safety training for all staff. test staff. Whenever possible, study visits were conducted within the patient’s usual Aboriginal medical service. Study participants could be accompanied by friends, family and staff. This facilitated communication and a sense of security and trust.
Over two years, we recruited 38 aboriginal patients and 52 eyes (some patients had BMD in both eyes). Patients were recruited from both Perth and Western Australia. When they enrolled, they were randomly assigned to receive a dexamethasone implant or an anti-VEGF agent called Avastin. A follow-up was carried out for checks and restatements. After 12 months, we analyzed all our data, in order to compare the safety and effectiveness of the two drugs.
The results showed that patients who received a dexamethasone implant gained an additional four letters on a standard eye chart, which equated to a 6.2% improvement in their vision. Those who received the anti-VEGF agent, meanwhile, lost 5.5 letters on average, a drop of 8.9%.
Taken together, these results represented a visual benefit of 15% (9.5 letters) for patients who received a dexamethasone implant. In concrete terms, this meant that the patients met the visual requirements for a private driving license. Those who received the anti-VEGF agent did not receive it.
This disparity was more pronounced in rural towns, where the dexamethasone implant had a 37% advantage (24 letters) over the anti-VEGF agent.
why it works
As we suspected, the reason for the better performance of the dexamethasone implant had to do with its less frequent, and therefore more pragmatic, dosing schedule.
Over 12 months, patients who were to receive four dexamethasone implant injections received an average of 3.3 injections. This means that, on average, they received 82.5% of the scheduled treatments.
Anti-VEGF patients, meanwhile, received 7.2 of their 12 scheduled injections. This equates to only 60% of their scheduled treatments and reflects the difficulty of attending monthly appointments in the real world. Anti-VEGF patients received more than twice as many injections as patients with dexamethasone implants, but ended up with poorer vision.
Not all results were positive. A third of patients who received a dexamethasone implant developed high pressure in the eye – a recognized side effect of steroid injections. Although not painful, it requires treatment with pressure-lowering drops and close follow-up, to prevent glaucoma.
Second, steroid injections accelerate the formation of cataracts (a clouding of the lens of the eye). This requires access to cataract surgery, which is not always easy to arrange in remote locations. Based on these caveats, we developed guidelines for the judicious use of dexamethasone implant in Aboriginal patients, published in March.
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Reducing the Burden, Bridging the Vision Gap
Although dexamethasone implants are not perfect, we believe the OASIS study offers hope of reducing vision loss and the “burden of treatment” for Indigenous Australians with diabetes.
The ability to perform culturally safe clinical trials means that new treatments could be evaluated in the same way in the future, taking into account patient input through community-controlled research.
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