The Australian eyecare sector is challenging the idea that vision loss with age is inevitable. This, combined with cutting-edge research from world-renowned experts, promising therapies, and ongoing efforts to enhance patient outcomes, position the country as a global leader in the fight against macular disease.
The notion that vision loss is an inevitable product of ageing is outdated, according to Macular Disease Foundation Australia (MDFA) CEO Dr Kathy Chapman.
Indeed, addressing the increasing prevalence of macular disease as the population ages is one the sector’s greatest challenges, but shaking the stigma that vision loss is a forgone conclusion as we age is a challenge of equal proportions.
“We do know that if people can be detected early and be monitored and get on to the right treatment pathway, vision loss doesn’t have to be the case,”
Dr Chapman says.
To drive this mindset, a key focus of the peak body’s ongoing and upcoming initiatives is to equip an increasing number of people with macular disease with accurate and relevant information about their disease. Dr Chapman says more widespread early diagnosis provides a hopeful outlook for disease management.
This can be attributed to technological advancements and to optometry adopting some of the responsibility of disease detection (which would have typically occurred at the level of the ophthalmologist). Now, more practices are incorporating OCT into their daily workflows.
“A lot of optometry practices have new technology and capabilities which allow them to see those signs and symptoms to refer people on early. I think that’s an exciting development,” Dr Chapman says.
On the future of macular disease
MDFA’s strategic priorities include community awareness, support services, advocacy, and funding research efforts to combat macular disease. Dr Chapman cites ongoing Social Impact Surveys as a significant area of investment for MDFA that are directed to people with various forms of macular disease.
“Our Social Impact Surveys are the largest snapshot of people living with macular disease in Australia,” Dr Chapman says. “We’re giving patients a chance to share their main areas of concern.
“This is a really important piece of research for MDFA because it helps us understand the bigger issues at a systemic level, what we should be advocating for, and how we can design our support programs to really answer people’s concerns.”
Beginning in 2021, each survey has a particular focus, with the most recent survey in 2023 exploring mental wellbeing. The results from this survey helped inform the formation of MDFA’s new My Eyes service being launched in May 2024.
My Eyes – the latest support and care initiative of MDFA – is a free service tailored to patients’ diagnoses. Piloted since October 2023, it serves as a safety net for patients in between clinic visits. As part of the service, MDFA personalises information based on disease stage, individual anxiety levels, and severity of vision loss, with a commitment to maintain contact over an extended period.
“It’s a way of being able to keep in touch with people in between their clinic visits with their eye health professional,” Dr Chapman says. “Rather than thinking they’re just calling us once or that we will provide as much information as possible, we tailor our support and stay in touch with people for a 12-to-18-month period.”
The forthcoming 2024 Social Impact Survey is focusing on the cost of treatments – a major barrier to treatment uptake and compliance in neovascular age-related macular degeneration (nAMD).
It has been demonstrated 20% of patients who begin their anti-VEGF intravitreal injections withdraw from treatment in their first year, and 50% withdraw by the fifth year.
“Cost and being able to be treated close to home are the two biggest reasons why people drop out,” Dr Chapman says.
With the results of the survey, MDFA has been able to direct attention to the federal and state governments to lobby for greater access to ophthalmology services in public outpatient settings.
“About 80% of people who require the intravitreal injections receive them in private ophthalmologist rooms and only about 20% of them are able to access them through public hospital outpatient clinics,” Dr Chapman says.
“We’ve talked to the government about looking at practice incentives to increase access to more bulk billed services, particularly for aged care pensioners. We’re also advocating for helping people with the cost of travel for treatment because if you live in a country area, you tend to have further to travel and more to pay,” Dr Chapman says.
Much of the discussions between MDFA and the government involve a long-term look at the economic benefits of increasing funding in this space. The foundation recently compiled an economic modelling report entitled ‘Investing to Save Sight: Health and Economic Benefits of Improving Macular Disease Treatment Resistant’.
“It was amazing to find that over a decade – and if we could get just 25% more people staying on their treatment course – the government could save up to $2 billion,” Dr Chapman says.
“Stopping people from going blind and accruing all the extra health and aged care costs as a result means that it is vital for government to be investing now.”
As part of Macula Month, MDFA is also launching updated nutrition guidelines for people with macular disease. The organisation completed a systematic review of all the published evidence on the association between diet and macular disease (more information is available on page 36).
“Fish, as well as a variety of fruits and vegetables, are all very beneficial parts of an eye-healthy diet,” Dr Chapman notes, with the research also uncovering disease risk factors such as alcohol – now reinforced in MDFA’s messaging.
Looking ahead, Dr Chapman would like to see greater referrals to MDFA to capture the largest possible patient base. As the foundation bridges the gap between clinic visits, it provides much-needed social support absent from traditional diagnosis and treatment regimes.
“We often hear people saying, ‘I wish I’d known about Macular Disease Foundation earlier’,” she says.
“MDFA is helping people live with the condition; the foundation wants to be here to help people live with the disease and to really enjoy the best quality-of-life with ongoing information and support.”
Leading the charge
Associate Professor Anthony Kwan works at the Queensland Eye Institute (QEI) and Mater Hospital in Brisbane. As a retinal specialist, AMD is a staple of his day-to-day work life.
He works closely with the MDFA on its medical and research committees, helps the organisation award grants to new prospective treatments, and guides patient support groups to optimise service delivery.
Dr Kwan places Australia at the forefront of macular disease developments due to the availability of treatments and clinical trials, and in terms of patient outcomes. As one example, Australia is a proven leader in vision preservation shown in the Fight Retinal Blindness! (FRB!) digital database.
The adoption of treat and extend regimens – involving progressive extension of treatment intervals up to 16 weeks – can be attributed to these better outcomes, according to Dr Kwan.
“With a treat and extend regime, patients’ results are likely to be better than treating as needed. Here, vision is more likely to be maintained if they adhere to the treatment,” Dr Kwan says.
The first approved macular disease therapies are reaching maturity – with anti-VEGF intravitreal treatments first entering the scene in 2007 (Lucentis) followed by Eylea in 2012. For several years, these have remained as the main treatment options for nAMD. More recently, Vabysmo (Faricimab) has entered the market and has given specialists more choice in the management of diabetes-related macular oedema (DMO) and nAMD.
While these treatments are still considered the gold-standard, the therapies have their drawbacks. In particular, treatments are not once-off, with patients requiring frequent, ongoing injections. This, coupled with the cost of private ophthalmology services, results in a significant dropout rate.
With treatment options available for nAMD, diabetic retinopathy and vein occlusion, attention is now turning to the other late form of AMD, geographic atrophy (GA).
So far, only two therapies have been approved for GA in the US – Syfovre by Apellis and Izervay by Iveric Bio – both in 2023. While both drug companies intend to bring their therapies to Australia (Syfovre has been submitted for TGA approval with Izervay following suit shortly), Dr Kwan says it is unclear when or if they will become available.
“These drugs are not approved in Australia, partly because there are some limitations,” he says. “They’ve been shown to slow down the progression of degeneration involved in geographic atrophy but that doesn’t necessarily improve the patient’s visual function. The other consideration is the long-term safety of these new treatments. So that’s why I believe the government has to carefully consider approving and funding these treatments.”
Dr Kwan, alongside the MDFA, lobbies individual state governments to improve treatment availability – as delivery of service differs between states, with some not providing certain treatments.
Dr Kwan points to NSW and the ACT who have not signed up for the Pharmaceutical Reform Agreement which means they do not have access to the pharmaceutical benefit scheme (PBS). That is, PBS subsidised medicines are not readily available in public clinics in these states and territories.
To overcome non-compliance of treatment, Dr Kwan says there are clinical trials for orally delivered agents that will hopefully have similar efficacy to intravitreal injections.
One example is the investigational drug danicopan – an oral complement factor inhibitor. It is currently in Phase 2 clinical trials, led by Professor Robyn Guymer at the Centre for Eye Research Australia (CERA), to test its effectiveness in slowing GA and asses its safety profile.
Elsewhere, the Port Delivery System designed for prolonged delivery of ranibizumab is being assessed in Phase 3 clinical trials. This system is surgically implanted into the eye and then requires an annual or biannual top-up which is considered more efficient than the current delivery of therapy each month or two.
Additionally, there is a new UNSW-developed molecule – called BT2 – that could be administered via an eye drop for nAMD. This is being commercialised by clinical-stage Australian biotechnology company Filamon Limited which hopes to have the therapy in clinical use within three years.
On the research horizon, Dr Kwan is hopeful for gene therapy to lead the charge, despite the discontinuing of the GT005 gene therapy clinical trial for GA last year.
“This would involve injecting the gene product for anti-VEGF therapy for nAMD into the back of the eye, where it would behave as an ‘intraocular factory’ and continuously produce the drug,” he says.
Elevating the treatment landscape
Professor Mark Gillies, director of the Macula Research Group (MRG) at the University of Sydney, says treatment outcomes from the clinical trials of therapies approved in the US for GA only serve to delay vision loss.
“Roughly, with two years of monthly injections, you defer vision loss that was going to happen in two years, to three years. That’s currently the major benefit that patients can expect – which isn’t amazing,” he says.
Dr Gillies says patients are not aware that the rate of expansion of their macular atrophy has been slowed, as treatments delay vision loss but do not improve vision. This may act as a driver for non-compliance.
To restore vision lost from macular atrophy, he says researchers are working to transplant retinal pigment epithelium and photoreceptors. Although still in early stages and not yet achieved, many groups around the world are working on it with Dr Gillies hoping there will be progress in the foreseeable future.
“There’s a lot of work in this area that will hopefully continue to develop and produce outcomes over the next few years, but at the moment, that’s not something that we can do with atrophic AMD,” he says.
Dr Gillies says the new generation of nAMD therapeutics – which includes Beovu by Novartis – are designed to be more potent than their predecessors and therefore last longer with increased intervals between injections.
“Beovu certainly appeared stronger than previous agents, but it had a higher rate of causing inflammation inside the eye, so it is only used occasionally for eyes that are very difficult to control with other agents,” Dr Gillies says.
Furthermore, in January 2023, Roche’s Vabysmo became the first TGA-registered bispecific antibody approved for the eye in Australia. It specifically recognises and blocks the activity of proteins known as angiopoietin-2 and vascular endothelial growth factor A, and joins an expanding list of approved anti-VEGF therapies for macular disease in Australia.
The other new VEGF inhibitor, high-dose Eylea, has recently been approved in the US and Europe. It has four times the dose (8mg instead of 2mg) of the original Eylea formulation that was released 10 years ago.
The FRB! Project – developed by Dr Gillies at the Save Sight Institute – has tracked real world outcomes of therapeutic outcomes. The project recently found that 40% of eyes with nAMD lesions that could not be inactivated by other VEGF inhibitors became inactive after introduced to Vabysmo when treatment intervals were lengthened by approximately three weeks. This occurred 12 months after switching to the new treatment.
Despite this effectiveness, Dr Gillies says that further research is required to determine whether the new treatments are associated with greater risks of intraocular inflammation than are found with existing agents. And even if they last longer – with some treatments administered every five or six months – it is believed that injections need to be continued indefinitely which is expensive for the government to fund.
Another significant development in this space, according to Dr Gillies, are projects focusing on macular telangiectasia type 2 (MacTel). The disease is sometimes mistaken for AMD due to similar symptoms and clinical signs, however, there is currently no available treatment.
Dr Gillies was the chief investigator of two major randomised Phase 3 clinical trials for NT-501, a treatment for MacTel. In study A the therapy, developed by Neurotech Pharmaceuticals, reduced the rate of expansion of atrophy by approximately 55%, and by around 30% in study B.
The drug is delivered through an implantable device which secretes ciliary neutrophic factor (CNTF) with controlled, long-term delivery. An implant that was removed from an eye after 15 years was found to still secrete the drug.
“It’s a real one and done procedure. MacTel currently doesn’t have any other treatment – so that’s a big breakthrough,” Dr Gillies says.
Furthermore, his research extends to defining the anatomy of the macula – what he describes as an ambiguous segment of the eye – to understand why it develops MacTel in particular, but also AMD and DMO.
As part of this, Dr Gillies says his team are among the first to grow and study human maculas from eyes donated for corneal transplantation ex vivo (in a culture chamber).
“Even though you get some disease in the peripheral retina, they’re much more focused in the central macula and that has a much greater effect on the patient as this is where the central vision is,” Dr Gillies says.
“There’s not a lot of research known about why the macula is so different. Everyone knows it’s anatomically different, but not of the biochemical and physiological differences which make it so susceptible to getting the diseases.”
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More than $700,000 funding awarded to six macular disease research projects
Port delivery system for neovascular AMD – A/Prof Anthony Kwan
