Patients diagnosed with late-stage age-related macular degeneration in Australia have entirely different prospects, depending on what form they have. But for those with geographic atrophy – still without a treatment – their fortunes may soon turn, creating a new set of challenges and opportunities, says PROF ROBYN GUYMER.
As one of Australia’s foremost experts on macular disease, Professor Robyn Guymer AM has a simple message for her eyecare colleagues: if you’re confronted with a geographic atrophy (GA) patient interested in the new wave of potential treatments, capture retinal images, ideally OCT and fundus autofluorescence (FAF).
Up until this point, a GA diagnosis led to a slow demise in patients’ vision. Without an approved treatment yet in Australia, they eventually lose their fine, central vision and often rely on low vision support and services to get by in life. Eventually, difficult discussions come about driving and their independence.
It’s a grim reality Prof Guymer has grappled with throughout her 28-year career, but one that could be addressed if two promising therapies already approved in the US are cleared for use in Australia.
This is the reason she wants Australian optometrists and ophthalmologists to begin imaging the macula with OCT (ideally with high scan density) and FAF scans. If they have access to the technology, it will help to obtain a baseline of patients’ GA lesions and determine who’s progressing and how fast. It’s all vital information that could inform which patients are best suited for treatments if approved by the Therapeutic Goods Administration and subsidised via the Pharmaceutical Benefits Scheme (PBS).
“If treatments are approved, ideally we’d like to know the growth rate before the patient started treatment as people progress at different rates and this information will be part of a complete picture to be considered when counselling patients,” say Prof Guymer, deputy director and head of macular research at Melbourne’s Centre for Eye Research Australia (CERA).
“It’s vital we begin capturing this information now so that in six to 12 months’ time, if a therapy is approved, we will be able to best counsel people considering opting for treatment.”
The Australian ophthalmic sector has been watching the GA therapy landscape closely after the US Food and Drug Administration (FDA) approved the disease’s first ever therapy in February 2023. Pegcetacoplan injection, developed by Apellis Pharmaceuticals and marketed in the US as SYFOVRE, was a historic moment for the macular disease community.
It was followed by another approval six month later, avacincaptad pegol intravitreal solution, marketed as IZERVAY by Astellas Pharma.
Since then, other markets haven’t been as swift to follow.
Shortly after pegcetacoplan injection became widely adopted in the US, rare occurrences of retinal vasculitis cases were reported.
Prof Guymer, who is on the international and local advisory board for Apellis, says while this raised safety concerns, there doesn’t seem to have been increasing numbers reported with ongoing uptake in the US.
She says the bigger challenge has been obtaining market clearance in Europe where regulators are yet to approve the therapy. One issue has been that the trials were not able to show a visual acuity benefit in the treatment group over the sham arm of the studies.
Instead, the first of two Phase 3 studies showed in patients with GA secondary to age-related macular degeneration (AMD) that pegcetacoplan reduced the rate of lesion growth through 24 months by 22% with monthly injections and 18% with every-other-month injections (OAKS study n=637). In the second study (DERBY n=621), this was 18% for monthly treatments and 17% for every-other-month. Both were compared alongside a sham group.
But Prof Guymer questions the emphasis on visual acuity when considering approving a GA therapy.
She says it is common to have good visual acuity until very late in the disease, but there is considerable loss of retinal function in the surrounding areas. The function of these surrounding areas can be tested by a technique called microperimetry.
That’s why, together with Associate Professor Zhichao Wu at CERA, they are working to develop a more appropriate perimetry test that can help detect changes in retinal function over time, and allow companies a better chance of detecting and demonstrating differences in retinal function with their treatments.
“It helps to think about the aims of treatment for GA like the aims of treatment for some cancers where extending life is the goal. With GA, it’s about slowing it down and seeing how much longer central foveal vision can be saved. If I can give you a year or two more allowing you to read and drive, that might be enough benefit to you to want to undergo the treatment regimen,” she explains.
“We know GA often starts out away from the dead centre of the macula and works its way towards the fovea, so that’s why we would not expect visual acuity to change in most people over the course of a 12-24 month trial. The FDA has understood that if you can save photoreceptors from dying, that’s got to be good for your vision and is an acceptable outcome.”
A whole new conversation
Prof Guymer remembers a time in her career having tough conversations with patients with neovascular AMD (nAMD), resigned to severe irreversible vision loss. But their fortunes changed in 2007 when the first anti-VEGF therapy was listed on the PBS.
While similar hope is held in GA, she says it’s important to differentiate how therapies will work for GA versus nAMD patients.
For example, with a nAMD diagnosis, essentially everyone is offered treatment.
“In nAMD, the aim is to stop people from losing more vision and in some cases potentially improve vision. You can clearly show people after a few injections that their retina looks much nicer too. It’s a slam dunk,” she says.
“Whereas in GA, patients are going to lose vision, just at a slower rate if they’re treated. Patients might wonder why they have been receiving theses injections for years and they’re still losing vision, why should they continue? But they most likely would have been worse if they didn’t undergo the treatment, so it’s all about how you can explain that to a patient.”
Prof Guymer is hopeful Australia’s first GA therapy will be approved in the next 12 months.
She says it’s widely acknowledged the emerging crop of treatments, if approved, are an important starting point.
“The bottom line is that GA is the commonest cause of poor vision in poeple over 50 years of age in Australia and here comes our first treatment that slows down the rate of growth. It’s a start and it’s certainly not the end of advances in GA management. No one thinks that injecting an eye every month is going to be the definitive way we will end up treating GA, but it’s going to get us used to identifying GA patients in the community, following their change over time, understanding risk and benefits of treatment and how treatments are perceived in the community,” she says.
“It’s going to slow down that rate of vision loss for patients and will reframe the discussion around the length of time we can save a person’s central vision. It’s a whole new conversation for us and for the patient.”
Bracing for GA patients
It’s also igniting discussion among Australia’s ophthalmic organisations. How can a stretched ophthalmology workforce treat a whole new patient group?
Already RANZCO has updated its Referral Pathway for Age-Related Macular Degeneration (AMD) Management to advise that GA patients should be non-urgently referred to an ophthalmologist if they are interested in a potential treatment or to learn more, so they can make an informed decision.
But finding capacity to administer GA injections is a major hurdle. Anti-VEGF injections are difficult to access in the public hospital system already, with most delivered in private clinics (some who bulk bill).
According to Prof Guymer, the challenge will be creating capacity for GA patients, while ensuring those potentially at greater risk of more rapid vision loss – nAMD and diabetic eye disease – don’t miss out.
But there are ongoing conversations within the eyecare community as to how to deal with this inevitable increase in patient load.
In terms of retinal imaging, it appears more optometrists are acquiring ultra widefield devices with FAF capability. Prof Guymer says that it might be possible to offer potential reading centres that could receive images to help identify patients with GA, including those who might fit certain criteria, making them ideal candidates for treatment, as well as those who may not be suitable.
This, as well as other initiatives, may need to be considered to determine who might fit criteria to possibly access public hospital clinics.
“There will most likely be a need to triage patients, but we will first have to wait for the government decisions on access to treatment and if there are any eligibility criteria for subsidised treatment via the PBS,” she says.
“Some studies have only allowed people with GA not affecting the foveal centre to be included, aiming to stop progression to the fovea. However, in the real world, even in people where atrophy has started encroaching on the fovea, vision can still be fairly good and as such stopping further encroachment would still be a worthwhile aim. It is these people who are desperately trying to keep driving vision for example.”
For Prof Guymer, as she sees her GA patients now, she feels there are more people than first expected that she would consider for treatment.
“Initially I thought maybe 10% of patients would likely consider the currently [US] approved treatments, but now it’s probably more like 50%. Whether they say yes given the side effects and the burden of having the injections is another thing.”
Either way, it will be an interesting 12 months for the GA community.
“We should know whether one or two drugs have been approved in Australia within the next year,” Prof Guymer says.
“There’s also several other GA trials under way that are also of interest. These are in gene therapy – a once-off treatment rather than forever ongoing treatments – there’s trials of oral medication, subcutaneous injections – all different ways to attack the same problem.
“In the next 12 months some of those trials will be read out, so we’ll know what else is coming not too far down the track. If a treatment gets approved, then patients will quickly know about it, and we need to get ready and ensure we can cater for them.”
More reading
The changing face of geographic atrophy
FDA approves Apellis’ SYFOVRE for first geographic atrophy treatment
FDA approves Iveric Bio’s IZERVAY for geographic atrophy
