WHEN 6/6 IS MISLEADING

GA is the late atrophic form of AMD. On OCT and fundus autofluorescence, the anatomy can look very clear: retinal pigment epithelium, photoreceptors, and choriocapillaris lost in a sharply demarcated area that enlarges over time. The patient in front of you is rarely that tidy.

The Snellen chart can be actively misleading in GA. A patient can read 6/6 on your illuminated Snellen chart and still say, quite reasonably, “I can see the letters, but I can’t read the sentence”. Faces take longer to recognise, subtitles are exhausting, and dusk driving may quietly disappear from daily life.

A patient might still read the bottom line but still have had to stop reading the newspaper because the centre of words keeps breaking up. Their spouse may hear ‘6/6’ and think the appointment has gone well. The patient knows it has not. That is not contradictory; it is typical of parafoveal atrophy.

GA can spare foveal acuity while damaging the visual tasks patients actually care about: reading speed, low-luminance function, face recognition, contrast, and the small daily indignities of missing part of a word. If the optometric record only says ‘6/6, early GA’, the referral can look calm when the patient’s life is already narrowing.

GA also behaves unevenly. Lesion location, baseline size, multifocality, fellow-eye status, and reticular pseudodrusen all change the likely course. Some eyes creep. Some move faster than anyone would like. The honest answer to “how long have I got?” is often that we can describe risk, but we cannot give a timetable for the individual eye in front of us.

WHAT THE NEW DRUGS DO

Two intravitreal complement inhibitors are now registered by the Therapeutic Goods Administration (TGA) in Australia for GA secondary to AMD: pegcetacoplan (Syfovre), a C3 inhibitor, and avacincaptad pegol (Izervay), a C5 inhibitor.1,2 Both require repeated intravitreal injection, with the aim of slowing enlargement of the atrophic lesion. They are not a general treatment for dry AMD.3,4

In practice, I am looking for threatened foveal function, enough remaining central function for slowing progression to matter, and a patient who understands that the benefit may be seen more clearly on imaging than in daily life.

When I look at the trial data, I do not start by asking whether the percentages sound impressive. That is the wrong question for GA. I ask whether slowing lesion growth is likely to preserve enough central function, for long enough, to justify repeated injections in this particular patient.

The registration trials used GA lesion growth on fundus autofluorescence as the primary endpoint. In GATHER2, monthly avacincaptad pegol met its 12-month anatomical endpoint, with reported slowing of about 14% using the square-root-transformed endpoint, or 18% using observed non-transformed GA growth.5 Two-year GATHER2 results continued to show reduced lesion growth, with reported treatment differences in the mid-teens to high-teens, depending on dosing analysis.6 Pegcetacoplan reduced GA lesion growth in OAKS and DERBY; OAKS met the 12-month primary endpoint, while DERBY did not meet its 12-month primary endpoint but showed a significant reduction in GA growth by 24 months.

The scan may show slower lesion enlargement, even when the patient feels no different. So far, the functional endpoints have been less persuasive than the imaging. Anatomical slowing may be worthwhile, even when the patient cannot feel it; that is the uncomfortable part of the counselling.

Then come the risks. Both drugs need standard intravitreal injection counselling: endophthalmitis, retinal detachment, intraocular pressure rise, inflammation, post-injection discomfort, and doing it again. Both are also associated with increased nAMD or choroidal neovascularisation (CNV), so ongoing OCT monitoring is needed. In the pegcetacoplan trials, nAMD was reported by month 24 in approximately 12% of monthly-treated eyes and 7% of every-other-month-treated eyes, compared with 3% of control eyes.7 Avacincaptad pegol has the same direction of signal: in GATHER2, macular neovascularisation was reported in 7% of treated eyes and 4% of sham eyes at 12 months, and in GATHER1 it was reported in 11.9% of the 2 mg group compared with 2.7% of the corresponding sham group at 18 months.6

A separate safety issue is retinal vasculitis: inflammation of the retinal blood vessels, which is uncommon but can be vision-threatening. Retinal vasculitis was not reported in the pivotal avacincaptad pegol program (GATHER1 and GATHER2), and a recent Bascom Palmer real-world series similarly reported no cases of retinal vasculitis.8 With pegcetacoplan, retinal vasculitis was not reported in OAKS and DERBY, but rare post-marketing cases have been described.7 The American Society of Retina Specialists Research and Safety in Therapeutics Committee report described a small post-marketing series, all after the first injection; early estimates put the rate in the order of one in 10,000 injections.9 I would, therefore, describe it to patients as rare, but serious enough that pain, redness, new floaters or a sudden drop in vision after injection should be reported promptly.

Getting the consent paperwork right is the easy part; making sure the patient has not heard ‘new treatment’ as ‘my vision may improve’ is harder. If that misunderstanding survives the first consultation, we are already starting from the wrong place.

Access remains a moving target. As of July 2026, both agents are TGA-registered in Australia for adult patients with GA secondary to AMD where the fovea is intact and central vision is threatened by lesion growth. Neither agent is currently listed on the Pharmaceutical Benefits Scheme (PBS) for GA. Although pegcetacoplan received a positive Pharmaceutical Benefits Advisory Committee recommendation in November 2025, its pathway to PBS listing is now uncertain following Biogen’s acquisition of Apellis. TGA approval does not automatically mean PBS funding or immediate practical access. The indication wording also matters: these treatments are not for early dry AMD, and the rationale becomes harder once established foveal atrophy is already the main cause of visual loss.

WHICH PATIENTS SHOULD BE DISCUSSED EARLY?

Lesion size matters, but it is only part of the referral decision. The patient to discuss early is usually the one with extrafoveal or parafoveal GA, a still-intact foveal centre, and central vision that is threatened by lesion growth. That is especially true if the fellow eye is poor, the atrophy is multifocal, or the patient is already describing functional loss despite apparently good acuity. The 6/6 patient whose reading has collapsed should not be dismissed as ‘too early’.

The harder calls are at the other end of the spectrum. A patient whose foveal centre has already been extensively lost may still deserve an opinion, but current TGA-approved treatment is aimed at GA where the fovea remains intact and central vision is threatened, not once the foveal centre has gone. The treatment rationale is also harder when the main visual loss is from advanced glaucoma, dense cataract, corneal disease, or another retinal problem that will swamp any GA benefit. Severe frailty, transport difficulty, needle intolerance, cognitive impairment, and private cost do not automatically rule treatment out, but they change the decision.

Then there is the patient who simply wants a cure. This is not a character flaw; it is a human response to a frightening diagnosis. But if the patient cannot accept treatment that may not make vision feel better, repeated injections may simply compound disappointment. I would rather spend another visit getting the explanation right than start treatment on a misunderstanding.

WHAT HELPS IN THE REFERRAL?

The most useful referral does not need to be long, but it should connect the scan to the patient’s function.

Acuity still matters, but it should not be the only number. Functional details often change how the consultation is framed: reading speed, missing letters, low-light function, face recognition, glare, driving confidence, or loss of a previously routine task. A note that the patient is 6/6 but has stopped reading is often more useful than another adjective describing the macula.

The imaging history is also important. A single OCT confirms anatomy; serial imaging tells us behaviour. Fundus autofluorescence is particularly helpful when it is available, especially if it shows whether the atrophy is parafoveal, multifocal, or moving towards fixation. If previous scans are available, the rate and direction of change matter. A small extrafoveal lesion that has barely changed over a year is a different problem from bilateral parafoveal atrophy that is enlarging towards fixation in a patient who is already struggling to read.

Fellow-eye status changes the decision. A patient with good fellow-eye function may tolerate uncertainty differently from a patient who is functionally dependent on the affected eye. Cognition, transport, anxiety about injections, and the patient’s understanding of what treatment can and cannot do all matter as well. A patient who cannot reliably get to the clinic is not making the same decision as a patient who can.

It also helps to know whether the patient is asking about treatment, anxious about treatment, or expecting treatment to improve the blind spot. Those three patients arrive in a very different frame of mind.

A cautious way to frame the referral is: “There are now treatments that may be relevant in some patients with GA. They do not reverse the damage, and access and suitability need to be assessed by the retinal specialist.” That keeps hope in the room without promising more than the evidence or the funding arrangements can carry.

DO NOT BORROW THE nAMD SCRIPT

nAMD has trained patients to think of injections in a particular way. Fluid dries. Distortion improves. A neighbour has three injections and sees better. That story is powerful, and it leaks into the GA consultation if we let it.

GA injections are different. They are not being given to clear fluid or restore damaged retina. They are being given to slow enlargement at the edge of an atrophic lesion. A patient with nAMD in one eye and GA in the other can easily think the GA treatment is inferior because the wet eye looks clearer after injection and the GA eye does not. It may be the same clinic and the same needle, but the treatment goal is completely different. Treatment may be doing its job when the patient notices nothing dramatic at all. That distinction needs to be made before the first injection, not after the third.

I still discuss percentages, but not first. First, I explain the disease, then what treatment is trying to do, then what it will ask of the patient. My usual wording is:

“This treatment is designed to slow how quickly the damaged area grows. It will not make your vision better, and it will not bring back vision that has already been lost.”

Then I check the understanding. “How would you explain this to your family when you get home?” If the answer is, “The injections are going to clear the blurry bit”, I have failed and need to go back.

I use the bushfire analogy often because Australian patients understand it quickly. The damaged area is land that has already burned. Treatment cannot regrow that bush; it aims to slow how fast the fire spreads into the surrounding land. Some patients look back at the autofluorescence image and say, in effect, “So that dark bit is already gone?”. Once that distinction is understood, the decision becomes more realistic.

THE BURDEN IS PART OF THE DECISION

Monthly injections, or injections every other month depending on the agent and phase of treatment, are not just a ‘treatment’. They are parking, transport, anxiety, time off work for a son or daughter, cost if unsubsidised, post-injection irritation, and the disappointment of coming back and still not seeing better. In Australia, dosing language also needs to be product-specific: pegcetacoplan is recommended every other month, while avacincaptad pegol is monthly for the first 12 months and then monthly or every other month thereafter.

I do not think “Do you understand the risks?” is enough here. A better question is: “Given the size of the likely benefit and the size of the burden, does this make sense for the way you want to live the next five years?”

Some patients want to start as soon as the option is explained. Others need to see another scan or two before the decision feels real. For a frail patient with transport problems, injection anxiety, and private cost, the likely benefit may simply not justify the burden of regular injections. Choosing not to proceed can still be a careful, informed decision.

Monitoring still matters if they decline treatment. Declining injections is not declining care. We still need to document progression, watch for neovascular conversion, update refraction where helpful, and bring in low vision support early rather than as a last resort.

LOW VISION CARE SHOULD START EARLY

Pharmacological treatment sits on top of supportive care, not instead of it. Smoking cessation, general health optimisation, diet, AREDS2 supplementation where indicated, low-vision rehabilitation, lighting, magnification, and contrast strategies still belong in the plan.

Patients often hear low vision referral as “nothing more can be done”. That is partly our fault if we introduce it too late. I prefer to frame it early as practical adaptation: making the remaining vision work harder while medical treatment, if chosen, tries to slow tissue loss.

This is exactly where optometry carries much of the work. Refraction, contrast, lighting advice, low vision aids, occupational adjustments, driving discussions, and repeated reinforcement of the treatment goal are the part of care the patient lives with between injections.

WORKING TOGETHER BETWEEN VISITS

Much of the useful work in GA happens between specialist visits. Earlier recognition, especially of extrafoveal disease, allows the treatment discussion to happen while there is still central function worth preserving.

Functional documentation remains valuable after the first referral as well. “6/6 but missing letters when reading and avoiding night driving” captures something the chart does not. It also gives the patient language for symptoms that are otherwise difficult to explain.

Between specialist visits, patients often return to their optometrist with the question they did not ask in the retinal clinic. They may also soften what they heard because the original message was unpleasant. A useful sentence is: “The injections are trying to slow the damage, not clear the blind spot. If things still feel difficult, that does not necessarily mean treatment has failed.”

Monitoring for conversion to nAMD remains important. New distortion, a sudden drop in vision, a new dark patch over fixation, or new subretinal or intraretinal fluid needs urgent assessment. Complement inhibitor treatment increases the rate of nAMD, and untreated wet conversion is one of the avoidable ways a GA patient can lose vision quickly.

Low vision support should come forward, not wait at the end of the pathway. Lighting, contrast, magnification, reading strategies, occupational advice, and driving discussions are not the last resort. They are part of care from the beginning.

For years we had the uncomfortable luxury of saying there was no treatment. Now there is treatment, but its benefit is modest, anatomical, and often not felt by the patient in the short term. The first injection should not be the moment the patient discovers what treatment cannot do. Before that visit, the patient should understand both sides of the decision: the possibility of slowing atrophy, and the reality of repeated injections, no recovery of lost retina, and ongoing need for low vision support. That is the discussion that needs to happen before treatment begins.

This CPD article was supported by an educational grant from Astellas Pharma Australia. The clinical opinions and editorial content are the author’s own.

References available at mieducation.com.