The year 2023 will be an exciting one in retina. There might be not just one but two treatments for advanced late dry age-related macular degeneration (AMD), or geographic atrophy (GA). After years of failures, there are 2 drugs with positive phase 3 data. As such, we at Retinal Physician thought it was high time to devote an entire issue to the state of the art in GA. We invited Eleonora (Nora) M. Lad, MD, PhD, associate professor of ophthalmology and the director of clinical research at Duke Eye Center, to be the guest editor for this issue, and she has assembled an amazing lineup of articles and authors. We cover topics from diagnosis, pathology, definitions, and imaging to following patients, patient perspectives, and updates on the latest clinical trials, and we hope you find this to be truly a special issue. As we edited this issue, I couldn’t help but be excited about what our future holds in this disease for which currently we have no treatment.

With no animal models to help with target development, treatment of dry AMD has been a tough nut to crack. To prove whether a certain mechanism of action was beneficial, companies must take a very expensive roll of the dice to simply test their drug in the only animal that is acceptable: humans. Moreover, the disease progresses so slowly that a proof-of-concept study must be at least 6 months long and, in some cases, 12 or more months long. Deciding on the primary outcome to prove efficacy is also a monumental challenge. If you choose visual acuity, regulatory authorities will ask for a >15 letter visual gain on the ETRDS chart, which is simply impossible. Choose an imaging outcome, and the only one that is currently accepted is prevention of photoreceptor loss. This works for late dry AMD where prevention of the growth of geographic atrophy is acceptable, but what about early dry AMD, where photoreceptor death may take years to develop? Ideally, we want to target the disease early, but there is no currently acceptable outcome besides vision for this disease.

These hurdles have made development in early dry AMD very difficult, and only a handful of companies have been brave enough to target this stage. Far easier is a study in late dry AMD. Hopefully, FDA approvals in late dry AMD will spur more development in this space, especially in early dry AMD. There are several large natural history studies ongoing. One goal of these studies is to find biomarkers in early disease that can predict loss of photoreceptors in later stages. With this ammunition, we can have more reasonable outcome measures to use to develop drugs for the far larger population of patients before vision-threatening problems like GA and neovascularization occur. RP