Geographic atrophy in practice: Three cases that defined the textbook

Geographic atrophy (GA) can coexist with exudative disease, progress along atypical pathways, and, in rare cases, turn out not to be age-related macular degeneration (AMD) at all. Those possibilities anchored a recent Ophthalmology Times Clinical Forum, where Yasha S. Modi, MD, MHS, vice chair of ophthalmology at Manhattan Eye, Ear, and Throat Hospital, part of Northwell Health, in New York, New York, served as moderator and case presenter, guiding a discussion on GA detection and treatment timing across 3 patient cases.

Treating GA and exudative disease at the same time

The first case involved a patient with fundus autofluorescence–confirmed GA sparing the fovea in one eye, while the other eye showed a hemorrhage indicating progression to concurrent exudative AMD alongside GA. Modi said the case raised the question of whether to treat both the exudative and atrophic forms at once.

Most clinical trials excluded patients who had both exudative disease and GA at enrollment, Modi said. However, the phase 3 programs allowed continued GA treatment plus anti-VEGF therapy for patients who converted during the study.

“This case is outside the realm of what we get in clinical trials, but this is a patient who shows up in the real world,” he said, adding that treating both conditions is a reasonable approach. Further imaging showed the eye had type 1 neovascularization without fluid at baseline alongside GA, and the patient progressed rapidly to exudative disease after starting anticomplement therapy, an effect also seen in post hoc analyses of the phase 3 DERBY (NCT03525600) and OAKS (NCT03525613) trials. Modi noted that optical coherence tomography angiography can help confirm type 1 neovascularization at baseline, and cited work by K. Bailey Freund, MD, and Emily Chew, MD, showing that subfoveal type 1 neovascularization without fluid may have a protective effect against atrophy progression in that area.

Catching progression before atrophy sets in

The second case involved a patient with high-risk features of intermediate AMD, including a large drusen burden and pigmentary changes, whose AREDS (phase 3 trial; NCT00000145) calculator score put their 5-year risk of converting to exudative disease at approximately 50%. The patient did convert, developing a pigment epithelial detachment (PED) that flattened with treatment, but the underlying drusenoid PED collapsed over the following years into an area of atrophy.

Modi said that progression pattern, running from PED to pigment migration to choroidal hypertransmission to eventual collapse, does not match the classic picture of GA expanding around and into the fovea. He noted that pivotal trials required a minimum GA size for enrollment, but incomplete retinal pigment epithelial and outer retinal atrophy, a precursor stage, is a strong predictor of progression to the complete atrophy that defines GA. “Our treatment paradigm should be focused on trying to treat those patients at an earlier stage before they go into progression to collapse,” he said.

Modi noted he would like to see the field move toward earlier intervention in AMD generally, treating patients at the high-risk intermediate stage before a drusenoid PED has the chance to collapse into atrophy. “Once somebody has GA, we cannot stop that progression,” he said. “All we can do at best is slow that progression, and then hope that the progression toward the fovea is less with therapy relative to the natural history.”

When GA is not AMD

The third case featured a young patient with extensive GA and an absence of drusen, a presentation Modi said would be easy to attribute to advanced AMD in a busy clinic. The patient’s age relative to the extent of atrophy prompted a broader workup, which turned up hearing loss and diabetes consistent with maternally inherited diabetes and deafness, a mitochondrial disease.

“These are patients [who] should ideally have been excluded in the DERBY and OAKS studies,” Modi said, referring to patients whose GA stems from non-AMD causes, noting that little evidence exists to guide treatment in this population. The case, he added, is a reminder that not every instance of GA is attributable to AMD.

Managing injection volume and IOP

Discussion also turned to the larger injection volumes, 0.1 mL, used with some GA therapies, and how to manage the resulting IOP spike. Participants raised using IOP-lowering drops before injection or gently pressing on the eye to help egress fluid. Modi said he finds bilateral large-volume injections challenging for patients, though he noted that some participants at the forum perform them regularly, which he found notable.