Getting to the root of geographic atrophy: Diagnosis and management

Geographic atrophy (GA), the end-stage of age-related macular degeneration (AMD), has recently become treatable with the advent of FDA-approved complement inhibitor therapies, presenting new opportunities—and challenges—for ophthalmologists. To explore these developments, Murtaza Adam, MD, director of clinical research at Colorado Retina in Denver, moderated an Ophthalmology Times Case-Based Roundtable® discussion at the EnVision Summit in Puerto Rico. During the session, the intricacies of 3 patients with GA were reviewed, highlighting clinical decision-making, treatment strategies, and emerging considerations in managing this progressive condition.

Case 1: Intermediate AMD and asymptomatic GA

A 70-year-old phakic woman had right and left eye visual acuities (VAs) of 20/30 and 20/25, respectively. The right eye had intermediate AMD, and the left eye had asymptomatic GA with a large nasal lesion that was 400 to 500 microns from the foveal center. The left eye was treated with pegcetacoplan (Syfovre; Apellis Pharmaceuticals) every 6 to 8 weeks.

Adam emphasized the importance of using multimodal imaging in this case because the GA was not obvious when relying only on fundus photographs or the examination for a diagnosis. Autofluorescence clearing showed the GA and optical coherence tomography highlighted the close proximity of the lesion to the central fovea, which underscored the potential need for treatment in this case.

“I think this case was a bit of a pivot from people who usually treat patients who have lost vision in one eye and are at risk of losing vision in their other eye. The clinical trial data for both medications that are available, i.e., pegcetacoplan and avacincaptad pegol [Izervay, Astellas Pharma], indicate early treatment is likely the best for patients with GA, and even in a patient that's asymptomatic with a high-risk GA lesion, starting treatment in these patients can be really, really beneficial,” he commented.

Case 2: Bilaterial dry AMD

This was a 79-year-old woman with bilateral dry AMD. The VAs were 20/60 and 20/50 in the right and left eyes, respectively. The left eye had GA. The patient lived in Europe for about 4 months of the year, which made treatment adherence difficult. This scenario provided a close look at the natural history of GA and how quickly the disease can progress and affect the central vision.

In this case, the nonfoveal lesion evolved over about a 16-month period when the left eye VA was 20/50 and ended at count fingers. The right eye that initially had no GA developed nonfoveal atrophy that progressed rapidly. Treatment with a complement inhibitor was started.

“This case underscored how quickly this disease can progress in certain patients, and even in the same patient, there can be heterogeneous presentations in which one eye progresses more slowly than the other. Obviously, in an ideal world, we would have treated the left eye before the central involvement occurred, but now we are staving off any progressive GA in the right eye,” Adam said.

Treatment adherence was difficult in this case because of the patient’s travel schedule, and many injections were skipped. Adam explained that the hope was that the lack of adherence to a consistent treatment schedule would not result in a worsened outcome and a quicker loss of vision.

“This case underscored both that before GA drugs became available, we did not know both how long it would take for a patient to progress from nonfoveal GA involvement to foveal involvement, and that the timeline in some patients can be rather quick. This case emphasizes another reason for us to have those conversations about GA treatment early and often,” he stated.

Case 3: Severe right-eye cataract and nonfoveal GA

This patient, a 79-year-old phakic woman, had a severe cataract in the right eye with count fingers vision (20/400) and nonfoveal GA in her better-seeing left eye (20/30). A large area of central GA was present in the right eye that was compounding the effect of the cataract, rendering her functionally monocular.

The initial consultation focused on the high risk of the left eye developing central involvement. Complement inhibitor therapy was started and scheduled on an every-6-to-8-week regimen to prevent more GA progression, Adam recounted.

The patient subsequently developed a choroidal neovascular membrane about 4 months after treatment onset and before symptoms developed.

Adam explained that complement inhibitors are associated with a higher risk of choroidal neovascularization (CNV) formation and offered some caveats.

“These are not typical neovascular AMD eyes, but eyes with usual lesions that are going to be nonfoveal and tend to be less active and less aggressive. I immediately start these patients on an anti-[VEGF] therapy, start a rapid treat-and-extend regimen, then ultimately restart the complement inhibitors,” he said.

Physicians attending the roundtable discussion reported that they generally follow an as-needed treatment paradigm: They treat the patients during 1 or 2 visits to quell the CNV and then resume complement inhibitor therapy shortly thereafter, treating the patient as needed with anti-VEGF if the CNV activity recurs. Others thought that it is relatively easy to treat the neovascular AMD; although this is a potentially scary risk factor for these patients, they are generally very treatable, and significant vision loss does not occur.

Roundtable revelations

An interesting talking point that emerged from the roundtable was how ophthalmologists start the conversation with patients about GA and how they initiate treatment. “Some doctors present the data and the option to start treatment at the first visit, while others tend to slow-play the conversation because there is a little bit of time. It was fascinating to hear how the perspective and uptake of treatment tend to be better when you give patients a bit more time and information, in contrast to just dumping all the information on them at once,” he said.

Regarding the initiation of treatment, with a novel class of drugs, intraocular inflammation is a concern. Adam explained that in his practice if a patient has an eye with central GA involvement and poor vision and the other eye is seeing well with nonfoveal GA, he typically starts a trial treatment in their worse-seeing eye to ascertain that they do not have antidrug antibodies or an autoimmune reaction to the medication and then reexamines the patient a few weeks later for retinal hemorrhage, vasculitis, and other inflammatory signs before starting in the better eye.

He described the roundtable discussion as a “spirited debate” in that some physicians started treatment immediately in the eye they wanted to treat.

“We learned from each other that the risk and the scariness of those complications are statistically low. However, we highlighted the importance of potentially using a worsening eye as a test eye before starting treatment in the intended eye. Obviously, in patients who have good bilateral vision and nonfoveal GA, there is the option to start bilateral treatment.”

He pointed out that the group agreed that starting treatment in one eye is probably safest, and then starting with bilateral treatment later is good practice. “It was really interesting to hear everybody's perspectives and how what was a straightforward thing in my mind actually can be done so many different ways,” he commented.

He continued, “I learned that many patients who develop secondary CNV from anticomplement treatment can be treated as needed after perhaps some loading doses of anti-VEGF. That actually changed my practice.”

Murtaza Adam, MD

E: madam@retinacolorado.com

Adam is director of clinical research, Colorado Retina, in Denver. He is a speaker and consultant to Apellis Pharmaceuticals and Astellas Pharma.