I’ve been preparing a talk on practical tips for treating geographic atrophy. Ever since wet age-related macular degeneration therapies became available, many patients have been clamoring for a GA treatment. Now, we have two Food and Drug Administration-approved drugs, pegcetacoplan (Syfovre, Apellis) and avacincaptad pegol (Izervay, Astellas), both of which have shown modest but significant reductions in GA growth over the course of two years but without any prespecified visual benefits. 

So, a debate rages as to whether we should be treating these patients.1,2 

On the pro side are several important points: 1) less GA progression will save more overall vision; 2) we don’t have the proper tests to assess visual function or the studies didn’t look at the right endpoints, which is why no visual benefit has been seen; 3) we should be treating even sooner when the atrophy is small and farther from the foveal center; 4) with more time, we will eventually see a vision benefit since the effect of the drugs improves the longer a patient is on it; and 5) this is the best thing available now and will help bridge the gap until something better comes out. 

Arguments against include: 1) without a definite vision benefit, it doesn’t make sense to treat; 2) these drugs are slowing down atrophy growth marginally when you delve into the numbers and they may just be delaying clearance of cells that are already not functioning, which explains the disconnect with lack of visual benefit; 3) the potential side effects are serious, including endophthalmitis, increased macular neovascularization risk and inflammation, of which occlusive retinal vasculitis is most concerning; 4) we shouldn’t make assumptions about potential visual benefits with earlier or longer treatment courses without solid evidence; and 5) the treatment carries a significant burden for patients and providers with ongoing monthly or bimonthly injections and may have a serious impact on health-care spending with unclear benefits.

One of the difficulties is that we don’t really know who will benefit from these treatments. We are left looking at each individual and assessing current vision, location and size of GA, fellow eye status, etc. 

The second issue is that we currently have no good way to tell if the treatment is helping. Looking at the post-hoc vision loss analyses, it looks like these drugs may be slowing things down by a few months at best. 

There’s no question that we need better tools to guide our decision- making. Imagine an algorithm that can project GA growth into the
future and then being able to superimpose the effect of treatment on altering that course. 

However, we ultimately need high-quality studies, not just post-hoc analyses, to convince us whether there’s indeed a functional benefit and quell this debate. RS




 1. Spaide RF, Vavvas DG. Complement inhibition for geographic atrophy: Review of salient functional outcomes and perspective. Retina. 2023;43:1064-1069. 

2. Del Priore LV. To treat or not to treat geographic atrophy – that is the question. Ophthalmol Retina. 2024;8:207-209.