STOCKHOLM — Current treatments for age-related macular degeneration (AMD) have proved effective and safe. However, these lifelong therapies involve frequent ocular injections. “It can be nerve-wracking for patients about to embark on this journey,” Lisa Olmos de Koo, MD, an ophthalmologist at the University of Washington Eye Institute at Harborview, Seattle, told this news organization.
At the American Society of Retina Specialists (ASRS) 2024 annual meeting, researchers from around the world presented results from clinical studies aiming at reducing the burden of AMD treatment by:
- Identifying patients at a higher risk for degeneration and vision loss who will be more likely to respond to treatment
- Developing gene therapies that promise to drastically reduce or eliminate the need for injections
- Testing novel drugs with mechanisms of action that use different pathways than currently available medications, offering patients more options and longer-lasting treatments
“It’s exciting to see the broad range of novel approaches in AMD treatments,” Dimitra Skondra, MD, PhD, a retina specialist at the University of Chicago, told this news organization.
Whom to Treat
Anti–vascular endothelial growth factor (anti-VEGF) therapies shook the AMD treatment scene when they were introduced in the early 2000s. “It was incredible,” Dr. Olmos de Koo said. Patients with wet AMD could finally see their vision improve with each injection. “It was a great motivator to begin therapy.”
However, patients with the advanced form of dry AMD involving geographic atrophy (GA) have had less luck. Pegcetacoplan and avacincaptad pegol, the only US Food and Drug Administration (FDA)–approved treatments for GA, slow the progression of the disease but do not restore vision. In fact, vision continues to decline. “Patients want to understand if their condition is worsening and whether treatment is necessary,” Dr. Olmos de Koo said.
Researchers are developing tools to help clinicians identify lesions that are more likely to grow and reach the fovea, causing vision loss.
For example, Cleveland Clinic’s Katherine Talcott, MD, presented an analysis of the GATHER1 and GATHER2 clinical trials that showed that spectral domain optical coherence tomography can be used to examine the integrity of the ellipsoid zone for predicting GA growth and treatment response. The retina’s ellipsoid zone contains densely packed mitochondria within the inner segments of the photoreceptor cells and plays a critical role in visual function.
Dr. Talcott and her team found that more severe baseline damage of the ellipsoid zone was associated with a faster growth rate of GA.
Another analysis of the same trials, presented by Dilraj Grewal, MD, associate professor of ophthalmology, vitreoretinal surgery, and uveitis at Duke Eye Center, Durham, North Carolina, showed that intravitreal administration of avacincaptad pegol efficiently reduced GA growth whether the treated eye developed macular neovascularization or not. Avacincaptad pegol is a complement factor inhibitor that aims to reduce complement-mediated inflammation and tissue damage in the retina.
Dr. Olmos de Koo explained that clinical trials have shown that more patients develop neovascularization when treated for dry GA than they would if left untreated. This has raised the question among clinicians whether the increased risk is a valid reason to avoid treatment. “This useful analysis tells us that there is still a rationale to continue treating GA, even while you’re concurrently treating the wet component with anti-VEGF therapies,” she said.
Another biomarker of GA growth is the position of the lesion at baseline. Daniel Muth, MD, an ophthalmology consultant at the Karolinska Institutet in Stockholm, Sweden, reported the results from a long-term, retrospective analysis of fundus autofluorescence in patients with GA. His semiautomated artificial intelligence–based analysis showed that patients affected bilaterally, but whose fovea was not yet affected, exhibited a faster GA growth rate than fovea-involving patients, with an approximate 15% risk for fovea involvement.
“Those patients whose atrophy has not yet affected the very center are the most likely to benefit from preventive therapy,” Dr. Olmos de Koo said. “Left untreated, a large proportion of them will develop atrophy that does affect their central vision — that’s their reading or facial recognition ability.”
“Potential predictors of rapid growth rates guide us clinically and allow patients to make more informed decisions about whether to pursue treatments that require frequent interventions,” Dr. Olmos de Koo said.
Forecasting the side to which the cost-benefit balance of treatment will tip for each patient is a complex decision-making process, she explained. “A patient is not a statistic, but these predictive studies are one important piece of the pie.”