Navigating geographic atrophy from biomarkers to bilateral therapy

A recent Modern Retina Case-Based Roundtable® examined the critical role of early detection of geographic atrophy (GA) to ensure timely intervention and reduce irreversible vision loss. Hasenin Al-khersan, MD, from Retina Consultants of Texas, in Bellaire, summarized the current treatment options for GA and their potential benefits and risks to guide management decisions.

Imaging is critical to early diagnosis. Autofluorescence is invaluable for diagnosing GA and following disease progression.

With a better understanding of various biomarkers, different autofluorescence patterns may help differentiate cases more likely to progress from those that are less likely to progress, he explained.

Optical coherence tomography angiography (OCTA), which is noninvasive and easily accessed and provides high-resolution images, is a mainstay for patient monitoring.

“Clinicians can track atrophic areas and ‘sick’ retina, where photoreceptor loss may be starting,” Al-khersan said.

GA management

Currently, no treatment algorithm exits to manage patients: Some participants treat only when vision starts to be affected, and others use atrophic lesions as biomarkers to start therapy, according to Al-khersan.

The 2 available therapies, pegcetacoplan (Syfovre; Apellis Pharmaceuticals) and avacincaptad (Izervay; Astellas Pharma US Inc), are steps forward in slowing GA progression, but they do not reverse existing vision loss, he noted.

Case discussions

Case 1. A 90-year-old woman presented with blurry vision (right eye, 20/70; left eye, 20/25) and increased difficulty reading.

OCT showed a hypertransmission defect in the right eye indicating non–foveal-involving atrophy, drusen, retinal pigment epithelial (RPE) changes, and loss of overlying photoreceptors. The left eye had atrophic changes farther from the central fovea. Autofluorescence findings indicated sick RPE and photoreceptors.

Treatment considerations were patient age, independence, and treatment frequency. Every-other-month pegcetacoplan injections were chosen. This patient wanted bilateral treatments to lessen the treatment burden.

The takeaway, Al-khersan explained, is when initiating therapy and deciding on bilateral injections, consider doing the worse eye first to rule out an inflammatory response. However, also consider the overall functional status of the patient and have that conversation with them.

Case 2. An 81-year-old man referred for an age-related macular degeneration (AMD) evaluation had no vision changes (right eye, 20/20; left eye, 20/25 [monovision]).

In 2022, superotemporal atrophic areas in the macula appeared bilaterally on fundus images and autofluorescence. OCT showed noninvolved foveas at that time when no GA treatments were approved. The patient then was lost to follow-up. He returned in 2024 with no vision changes. Comparison of the OCT changes at both time points showed enlarged lesions and new lesion formation below the fovea in the newer images, more in the left eye, necessitating treatment.

The patient opted for monthly bilateral treatments with pegcetacoplan and avacincaptad. Ten months later, the lesion growth continued and some coalesced below the fovea bilaterally.

The key point is emphasizing that GA worsening will occur and that if patients stop treatment, the progression may be more rapid. In this case, the progression was documented.

Case 3. A 90-year-old man with decreased vision bilaterally had a history of a choroidal neovascular membrane in the left eye.

OCT showed atrophy in the right eye near the fovea. The left eye had subretinal fibrosis with areas of hypertransmission at the edges of the fibrosis more centrally. The vision was 20/25 in the right eye and 20/200 in the left eye, likely due to the membrane. No fluid was present.

In this complex case, the difficulty in the left eye was determining how much atrophy resulted from wet AMD and from GA. “This matters because the effect of these drugs on that type of atrophy is unknown. An underlying GA process should be identified before starting treatment with anticomplement therapy,” Al-khersan said.

Fluorescein angiography or OCTA is useful in patients without a choroidal neovascular membrane to detect underlying/indolent neovascular membranes, thus informing clinicians of the risk of activating/converting to wet AMD during treatment.

This patient opted for bilateral treatments following a discussion of the case complexities. The left eye was treated first. The treatment was well tolerated with no inflammatory response. Treatment in the right eye began 1 month later.

Two months later, the right eye was stable; new intraretinal fluid in the left eye was considered reactivation of the membrane treated with complement therapy.

Al-khersan noted that he often administers complement inhibitors and anti-VEGF drugs on the same day, and patients tolerate this approach well.

This patient was treated with aflibercept (Eylea; Regeneron Pharmaceuticals) and pegcetacoplan concurrently in the left eye. The patient was treated at 8-week intervals with pegcetacoplan with concurrent aflibercept in the left eye, and the wet AMD was well controlled by that regimen.

One month later, after the initial anti-VEGF treatment, the fluid resolved.

Al-khersan concluded, “We’re excited to offer our patients new treatments that were not previously available, and these discussions are a great way to advance our field and achieve better patient outcomes.”