With new treatments for geographic atrophy in the pipeline, Royal Australian and New Zealand College of Ophthalmologists (RANZCO) has updated the AMD referral guidelines that optometrists use to direct patient management.

Geographic atrophy (GA) is one of two late forms of age-related macular degeneration (AMD), which until now has remained untreatable. With two treatments being recently approved in the United States, and several more in advanced stages of clinical trials, this is all about to change. Both currently approved drugs work to block the complement pathways in the eye by way of regular intravitreal injection. Apellis’s pegcetacoplan (Syfovre), inhibits complement factor 3 (C3) while Astellas’s avacincaptad pegol (Izervay), targets the complement factor C5.1,2

With regard to Australia gaining access to these treatments, Apellis has stated that the regulatory evaluation is in process with the Therapeutic Goods Administration (TGA), while Astellas Pharma is planning to submit to the TGA in the near future.

With the era of treatment for GA upon us, it is imperative that we review our current management of GA and update it accordingly so that it is fit for purpose. Many people with AMD are first alerted to the onset of GA by their optometrist on routine visits, often before any specific symptoms arise. Therefore, it is often community-based optometrists who will be first to identify people with GA and to start a conversation about management.

CURRENT MANAGEMENT

Current management of GA, in line with R ANZCO AMD referral guidelines, and Optometry Australia’s Chairside Reference for AMD, is for optometrists to explain their disease, identify and improve risk factors, recommend use of an Amsler grid, optimise spectacles, refer to low vision support services as appropriate, and review in six to 12 months, depending on individual need.3

Currently in ophthalmology practise, many patients with purely the GA form of late AMD, may only be seen once, or irregularly, until they start to experience vision loss, and as such, are referred back to their optometrist for ongoing review. Atrophy can also occur in the setting of neovascular AMD and these patients may also benefit from the same GA interventions, but are usually under the ongoing care of an ophthalmologist.

COUNSELLING FOCUS IN NEW GUIDANCE

The R ANZCO AMD guideline working group, which together with stakeholders devised the initial referral guidelines over five years ago, reconvened to specifically work on an update of the guideline with regard to GA. Together with stakeholders, a new guideline has been developed, approved by the College (Table 1), and is available on the College website: ranzco.edu/ home/policies-andguidelines/referral-pathway.

Specifically, the guidelines for AMD are now centred on the appropriate counselling of a patient with GA, with respect to potential treatment. Not everyone with GA will be interested to learn about these new advances, but everyone should be given the opportunity to consider them. To this end, if a patient with GA is interested in a potential treatment or even to learn more about the treatments to enable them to make an informed decision on treatment, the guidelines ask that these people be non-urgently referred to an ophthalmologist.

This referral will allow baseline imaging to be performed to help confirm that the atrophy is as a result of the late stages of AMD and not due to another cause, such as inherited retinal disease (IRD). It is often very hard, and sometimes impossible clinically, to be certain of the underlying cause of atrophy. High quality, multimodal imaging (MMI), including optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging, will in many cases, help to determine the cause. This is important now as the treatments will differ, as currently there is no evidence that the complement inhibitors are beneficial in IRD, and IRD may soon have its own specific treatments.

Another benefit of MMI is that there are characteristics that will allow the determination of the risk of fast progression, a metric which will be critical when considering treatment. Features such as the background FAF, the presence of reticular pseudo-drusen (RPD) and the number, size and location of the lesions, all contribute to an overall risk picture for each individual patient.

Another reason to obtain baseline imaging at the site where treatment is likely to be decided

upon, is to enable longitudinal evaluation of the progression rate, which is only really pragmatically possible if the images are taken on the same device in the same location. This way, growth rate over time can be accurately determined, and this will be an important factor when considering whether or not to recommend treatment.

For all these reasons, referral to an ophthalmologist, who is able to perform the imaging and determine these characteristics, will ensure the patient has the maximum information about their own GA to make a well-informed decision regarding treatment. Starting to record the baseline characteristics now, even before treatments are approved in Australia, will ensure that there is time for follow-up images before treatment starts, to determine the growth rate. Armed with this imaging information, together with consideration of the fellow eye, as well as other ocular diseases and personal circumstances, the ophthalmologists will be able to outline a management plan.

We acknowledge in the guidelines that currently it may not be possible for public patients to be referred to see an ophthalmologist, as outpatient clinics in public hospitals have limited ability to see GA patients. However, when treatments become available on the Pharmaceutical Benefits Scheme (PBS), this is likely to change with more access to treatment becoming available.

We also acknowledge that there will be additional challenges to overcome in regional and remote locations if we are to be able to offer equitable access to these new treatments.

The guidelines also highlight the need to become familiar with the early signs of atrophy in AMD as the messaging to patients with these changes will differ from messages to those without these early signs. Recognising the early OCT signs of nascent GA should prompt a discussion about their presence and the likelihood that there will be interventions that will become available and may be beneficial in the future. This is especially true if interventions for GA become very low risk and easy to deliver, as then the hope will be to start earlier, before there is considerable loss of retinal cells.

We are all privileged to be working in eye care at the dawn of a new era for people with AMD. Working together will ensure the best management and outcome for these patients with GA.

Professor Robyn H. Guymer AM MBBS FRANZCO PhD is an ophthalmologist with medical retinal subspeciality training. She is Professor of Ophthalmology at the University of Melbourne, Deputy Director of the Centre for Eye Research Australia and Chair of the RANZCO AMD referral guideline working group. Prof Guymer sits on advisory boards of Apellis, Genentech, Roche, Novartis, Bayer, Belite Bio Inc, AbbVie, and Janssen.

References
1. FDA approves Syfovre (pegcetacoplan injection) as the first and only treatment for geographic atrophy, a leading cause of blindness (media release, 17 February 2023) available at: investors.apellis.com/news-releases/news-release-details/fda-approves-syfovretmpegcetacoplaninjection-first-and-only. [Accessed 17
February 2023].
2. Astellas Pharma Inc., Iveric Bio receives US FDA approval for Izervay (avacincaptad pegol intravitreal solution), a new treatment for geographic atrophy (media release, 4 August 2023) available at: prnewswire.com/newsreleases/iveric-bio-receives-us-fda-approval-for-izervayavacincaptadpegol-intravitreal-solution-a-new-treatmentfor-geographicatrophy-301894042.html[accessed 8 August 2023].
3. Hart, K. M., Abbott, C., Ly, A., et al., Optometry Australia’s chairside reference for the diagnosis and management of age-related macular degeneration (2020). Clinical and Experimental Optometry, 103(3), 254–264. DOI: 10.1111/cxo.12964.