In pivotal clinical trials, complement inhibition therapy has been shown to slow the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) by about 25% to 34% after ~2 years.1,2 Subsequently, longer-term follow-up demonstrated that patients derive more pronounced slowing of progression the longer they are on therapy, highlighting the need for long-term compliance.3,4 Importantly, certain subpopulations in the pivotal clinical trials experienced markedly slower lesion growth on treatment, suggesting a need for careful patient selection as the use of complement inhibition therapy grows in real-world practice.
Considerations for Patient Selection
In my thinking, the ideal candidate to have a conversation about therapy is someone with earlier GA—specifically if there are small lesions outside the fovea—that is starting to cause symptoms, but still maintains good vision. It is particularly helpful if I have been following the patient over time to identify the lesion’s growth rate. If not, I look for hallmark characteristics associated with faster growth. While patient selection is ultimately individualized, the phenotype I am describing here (early, extrafoveal GA, at risk for rapid progression, and experiencing some visual symptoms) is most likely to benefit from therapy and most likely to want to stay on treatment over the long haul.
Thinking About
Long-Term Compliance
Initiating GA treatment is not urgent in the same way it is for exudative AMD. Once I identify a candidate, I prefer to introduce the topic of treatment and establish the goal (to slow progression rather than to reverse the disease course). But then, I give them time to think about whether they want to move forward. In situations where I deem it too early to start treatment, I may opt to follow the patient for 6 to 12 months to gauge their rate of progression before revisiting the notion of treatment.
There are factors beyond the clinical to consider before starting treatment. We must also candidly discuss with patients their ability to attend regular clinical visits, the treatment’s affordability, and potential quality-of-life disruptions if the patient is infirm or has concomitant medical conditions.
Establishing a Plan
that Builds Long-Term Compliance
Once the decision is made to initiate complement inhibition therapy, I try to make compliance as easy as possible for the patient, which largely means balancing the treatment’s frequency, burden, side effects, and efficacy. The clinical trials for both pegcetacoplan (Syfovre; Apellis) and avacincaptad pegol (Izervay; Astellas) established that patients derive benefit when dosed every 6 to 8 weeks. Some patients with more aggressive disease may be willing to accept more frequent retreatment, whereas those who live far from the clinic may be better suited for 8-week intervals.
There is no literature yet on patients lost to follow-up while on GA therapy, nor what effect poor compliance may have on slowing progression. My sense is that compliance in the short-term has not been a significant problem, but it does require a constant dialogue with patients to remind them of the goals of therapy to keep them on board. n
1. Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402:1434–1448
2. Khanani AM, Patel SS, Staurenghi G, et al; GATHER2 trial investigators. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet. 2023;402(10411):1449-1458.
3. Wykoff CC, Holz FG, Chiang A, et al; OAKS, DERBY, and GALE Investigators. Pegcetacoplan treatment for geographic atrophy in age-related macular degeneration over 36 months: data from OAKS, DERBY, and GALE. Am J Ophthalmol. 2025;276:350-364.
4. Gahn G, Kaiser PK, Khanani AM, et al. The 18-Month efficacy of avacincaptad pegol in geographic atrophy: pooled results from GATHER1 and GATHER2. Invest Ophthalmol Vis Sci. 2024;65(7):4400.
