Treatment options for patients with geographic atrophy

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Reviewed by Carl Regillo, MD, FACS

Carl Regillo, MD, FACS, director of the Retina Service at Wills Eye Hospital, Philadelphia, Pennsylvania, discussed the importance of a timely diagnosis and treatment to preserve vision in patients with geographic atrophy (GA) and the opinions of discussants during a recent Modern Retina Case-Based Roundtable.

“As our patient population grows larger and older, GA is going to become an increasing problem. We look forward to better treatments in the future that can help us manage this growing, major public health issue,” he said.

Over time some GA emerges from intermediate age-related macular degeneration (AMD), but it is more likely to develop earlier in eyes with high soft drusen load. Even many patients with wet AMD that is well managed with anti-VEGF agents often develop some GA as years on therapy go by. The good news is that anti-VEGF therapy does not appear to affect or exacerbate GA development. That being said, it is a potentially involved management process to address both problems simultaneously in a given eye.

Diagnosing and treating GA

Increasing numbers of patients are being referred to retinal practices by eye care clinicians; however, while optical coherence tomography (OCT) is ubiquitous in practice, referring doctors do not always recognize GA, especially in its early stages. “We really want to diagnose GA before there is a significant visual deterioration because we can only slow progression with newly available treatments. We can’t stop or reverse the damage associated with GA,” Regillo said.

GA progression varies markedly among patients. The characteristics predictive of more rapid progression are the presence of larger, multifocal, nonsubfoveal lesions; those associated with hyperautofluorescence along the border of the lesion with fundus autofluorescence imaging; and eye with reticular pseudodrusen, Regillo explained. This knowledge is important for counseling patients about the prognosis for future vision problems.

New therapies

In 2023, the field of ophthalmology saw the introduction of 2 intravitreal drugs that potentially can slow GA growth: pegcetacoplan (Syfovre; Apellis Pharmaceuticals) and avacincaptad pegol (Izervay; Iveric Bio), both of which are intravitreally injected complement inhibitors. Pegcetacoplan specifically blocks C3 and avacincaptad blocks C5, both of which are downstream complement components that effectively shut down or block all complement pathways. “The result is less macular tissue damage, less death of retinal pigment epithelial [RPE] cells with decreased RPE cell dropout over time,” Regillo said.

The pivotal phase 3 studies that included patients who were on the verge of or had started experiencing vision loss showed that both drugs seemed to reduced GA growth by up to 20% or so over 12 to 24 months.

The studies also showed that the benefits of treatment of nonsubfoveal lesions were greater because of the faster growth rate, and drugs that slow the growth rate have the potential to work better in that setting. While patients with nonsubfoveal lesions did better, all patients benefited to some degree with a decrease in growth of GA.

Regarding the efficacy of these drugs that were either injected monthly or every other month in clinical trials, the study results indicated that the every other month regimen worked almost as well as monthly injection treatment. While GA growth is not stopped, the progression of GA and associated visual dysfunction is slowed to some degree.

The potential adverse effects include increased rates of choroidal neovascularization, with patients treated bimonthly having much lower rates. There is also a small risk of endophthalmitis and intraocular inflammation, the rates of both of which would be expected to be lower with bimonthly treatment compared to monthly treatment.

Rarely intraocular inflammation after treatment with pegcetacoplan has been associated with retinal vasculitis and vascular occlusion, and some cases patients had permanent vision loss, none of which occurred during the clinical trials.

Case discussion

A 78-year-old man with bilateral GA–reported symptoms of difficulty reading in the right eye (OD) for about 6 to 12 months. He had poor vision in his left eye for over 3 years. The visual acuity OD was 20/50. His visual acuity in his left eye (OS) was counting fingers. OCT imaging showed a small multifocal GA lesion OD and a larger, foveal GA lesion OS.

The roundtable participants agreed both that this patient was a good treatment candidate and that treatment should be started in the eye with better vision. Regillo recounted that he began every-other-month treatment with pegcetacoplan in the right eye to slow vision loss; the left eye vision had too much atrophy to benefit from treatment. There was a discussion of injecting the worse eye first as a test of drug tolerance, considering the possible rare adverse effects of retinal vasculitis with occlusion, which to date has only occurred after the first injection of pegcetacoplan.

In 2 other cases, 1 or both eyes had wet AMD and were doing well with exudative control on anti-VEGF injections. Over several years, these patients began to develop GA with significant progression and symptoms of visual decline.

One case had very rapid progression over 12 months. The fundus autofluorescence image showed considerable enlargement of a moderately large multifocal GA lesion, and the patient was being treated with ranibizumab injections (Lucentis; Genentech) every 8 weeks. Regillo discussed with the patient concomitant treatment of GA with anti-VEGF injections to minimize the office visit burden.
He advised that the injections be administered at least 30 minutes apart and injection of the smaller volume (0.05 mL) anti-VEGF injection be first, followed by the larger volume (0.1 mL) complement inhibitor.

When presented with the option of undergoing the 2 injections on the same day, the patient opted to be treated on 2 separate days and returned a week or 2 later for a second injection. Treatment was maintained on an every-8-week regimen of anticomplement therapy in addition to the anti-VEGF therapy.

Another patient had bilateral wet AMD and bilateral GA that was growing and starting to impact vision with acuities of 20/100 OD and 20/80 OS and moderately large GA involving the foveal center in both eyes (OU). This patient was receiving anti-VEGF therapy OU every 12 weeks. When presented with the option of also treating the GA also, the patient opted for GA treatments in 1 eye (OS) every 6 weeks to preserve vision as long as possible.

A consideration when treating an eye with 2 intravitreal drugs on the same day is the effect on the intraocular pressure in patients with glaucoma. “We should proceed cautiously in these cases. If the intraocular pressure remains elevated in patients with glaucoma, a paracentesis might need to be performed. For those patients, it may be best to perform the injections on separate days,” Regillo said.

The group discussed the development of secondary choroidal neovascularization in patients receiving GA treatments who are doing well with injections every 6 or 8 weeks. If signs of exudation are seen, anti-VEGF therapy should be started. This raises the question about the patient remaining on GA treatment. This is an individual patient consideration, Regillo explained. For example, if the GA is very advanced, maybe not, but if it is early, the patient may still experience a visual benefit from GA treatment.

Regillo concluded that it makes most sense to treat patients with GA earlier before they have severe vision loss and to be mindful of the potential adverse effects of both GA drugs.

“Patients need a lot of counseling about these drugs. Because the decision is not an urgent one, patients can take time to weigh the benefits and risks of these therapies. These are going to be ongoing, potentially indefinite injections anywhere from every
4 to 8 weeks [apart],” he said.

Almost all roundtable participants agreed that it made the most sense from a risk-benefit standpoint to treat every 6 to 8 weeks, rather than every 4 weeks. However, the schedule must be tailored to the patient’s needs, their ability to get to the office, and whether 1 or both eyes also need treatment for wet AMD.

“This is a complex dialogue to have with patients that involves education not just at the start of treatment but thereafter to keep them engaged and derive the best benefits out of these therapies,” Regillo concluded.