Challenges for young physicians treating patients with GA

A recent Modern Retina Case-Based Roundtable highlighted the management of geographic atrophy (GA) and how young physicians and fellows can shape patient care, according to Samuel A. Minaker, MD, who reviewed the roundtable. The discussion was aimed at clinicians in an academic setting caring for many patients with diabetes or glaucoma.

The gathering provided an opportunity for clinicians who were less experienced with GA associated with age-related macular degeneration (AMD) to learn about the use and challenges of GA medications in this patient population.

“These challenges will shape how they approach these patients. We discussed different factors that initiate treatment and when we stop treatment,” commented Minaker, an assistant professor in the Department of Ophthalmology at Rush University in Chicago, Illinois.

Two drugs, avacincaptad pegol intravitreal solution (Izervay; formerly Zimura; Astellas Pharma) and pegcetacoplan injection (Syfovre; Apellis Pharmaceuticals), are available for treating GA.

When to start and stop treatment

If patients with GA are symptomatic, treatment is warranted, Minaker noted. The most challenging patients are those unaware that there is a GA lesion growing closer to their central macula. Starting treatment can slow that growth.

Another topic of discussion was using GA medications in patients with wet AMD who have developed atrophy. When Minaker’s patients develop GA with AMD, he continues the anti-VEGF injections.

Both GA medications are associated with inflammation that develops after the first injection, making that the riskiest time point, Minaker said. He explained that he stops therapy when a patient sees a lack of benefit. The timing of medication dosing (ie, on the same or separate days) was another consideration, based on patient preference.

Treatment efficacy

The roundtable participants believed that pegcetacoplan generally was more efficacious for slowing GA, based on clinical trial data. Minaker also noted the importance of discussing the nuances of treatment regarding patient expectations. The important factor is that the drugs do not stop GA but only slow it over time, he said. They also discussed that, for both medications, the treatment effect increases over time.

A surprising finding in the phase 2/3 GATHER1 (NCT02686658) and phase 3 GATHER2 (NCT04435366) studies was that the every-month dosing regimen of avacincaptad pegol was slightly less efficacious than every-other-month dosing. Mentioning the potential for inflammation, ischemic ocular neuropathy, and conversion to wet AMD is also important when educating patients about the treatment, Minaker said.

Representative cases

Case 1.

A 78-year-old active pseudophakic patient had visual acuities of 20/40 and 20/25 in the right and left eyes, respectively. The patient had a history of AMD and hypertension. Imaging showed complete outer retinal atrophy that corresponded to patches of hypoautofluorescence and some areas on the border with hyperautofluorescence.

Factors that play into the scenario for patients with similar images and visual acuity levels include age, lifestyle, activity, and goals that may affect treatment decisions. For example, a 95-year-old patient with the same visual scenario may be apprehensive about treatment. That case raises questions about the frequency of monitoring the patient and the imaging used.

This patient chose monthly dosing to hopefully decrease the GA progression. After 18 months, the patient converted to wet AMD, and he opted for same-day dosing with the GA and anti-VEGF drugs to minimize appointments.

Case 2.

A 76-year-old man had wet AMD bilaterally. Fibrosis developed in the right eye in 2015, and atrophy developed bilaterally. In the left eye, the atrophy was threatening the fovea.

The patient had been on an every-8-week regimen of aflibercept (Eylea; Regeneron Pharmaceuticals) administered bilaterally. The patient chose to continue treatment, despite worsening vision to counting fingers in 20/20. The patient understood that he would continue to lose vision because of GA progression.

Following discussion, the patient opted for treatment with pegcetacoplan initially in the worse eye and later in the fellow eye. The patient chose to have both injections administered on the same day because of his travel schedule.

Key takeaways

The biggest takeaway was the discussion of the data from the clinical trials of the GA medications and patient selection. “All attendees thought that these medications, if used earlier, would save more vision and that there would be some patient benefit,” Minaker said.

Another important aspect was that every-other-month dosing led to greater treatment adherence. Reducing the treatment burden makes it easier for patients to be more adherent. When their patients converted to wet AMD and wanted same-day injections, participants learned how to tailor treatment to individual patients.

Regarding the second case of wet AMD with atrophy, the patient’s 10-year imaging history clearly demonstrated progression over time that ultimately affected almost the entire macula in the worse eye and the progression in the better eye over time.

The participants were able to see the benefit of the GA drug for this patient and a way to accommodate his travel schedule with every-8-week dosing.

Another observation was provided by a glaucoma fellow who, when treating a patient who would ultimately go blind, suggested that physicians should not give up and not treat the patient but instead suggest ownership of the disease and provide the highest level of vision possible for as long as possible. Minaker agreed that this approach would be more empowering for patients.