Dual Therapy for Advanced AMD Found Safe in Real-World Study | ASRS 2025

Patients with advanced age-related macular degeneration can safely be treated with a combination of anti-VEGF and anti-complement therapies, according to the results from a real-world study, which was presented at the American Society of Retina Specialists (ASRS) annual meeting being held in Long Beach, California.

Edward H. Wood, M.D.

Researchers in this study, which was presented by Edward H. Wood, M.D., with the Austin Retina Associates, wanted to understand the real-world safety of combined treatment for geographic atrophy (GA) and neovascular or wet age-related macular degeneration (nAMD), administered either simultaneously or sequentially.

Geographic atrophy is an advanced form of dry age-related macular degeneration. It involves the death of cells in the macula, the central part of the retina, leading to progressive and permanent vision loss. Wet AMD happens when abnormal blood vessels grow and damage the macula. It is a less common type of AMD but causes faster vision loss.

Intravitreal anti-vascular endothelial growth factor (VEGF) and anti-complement therapies are used to treat age-related macular degeneration. Anti-VEGF drugs, such as Susvimo (ranibizumab) implant, Eylea (aflibercept), Beiu (brolucizumab) and Vabysmo (faricimab), which reduce blood vessel leakage and growth. They’ve been used primarily as monotherapy.

Anti-complement drugs, such as Syfovre (pegcetacoplan) and Izerway (avacincaptad pegol), inhibit the complement process and address the inflammation that can damage retinal cells.

The two types of therapies target different but interconnected pathways involved in AMD. In some cases, patients may require both types of therapies. Patients with both wet AMD and geographic atrophy in the same eye or progression of geographic atrophy after treatment with anti-VEGF drugs may qualify for dual treatment.

In one study published earlier this year of patients in a Medicare Advantage plan, the prevalence of geographic atrophy was found to be 0.48% to 0.56%. The prevalence of wet AMD was found to be 1.2% to 1.3%. Approximately 25% of patients with geographic atrophy also had wet AMD.

In the study presented at ASRS, researchers conducted a retrospective, non-randomized, consecutive case series of all eyes receiving dual anti-VEGF and anti-complement intravitreal injections throughout the Austin Retina Associates network. They reviewed electronic medical records (EMR) for patients with at least two injections of intravitreal anti-VEGF and anti-complement therapy with at least 30 days of follow-up.

Patients receiving dual therapy were classified into the following groups: dual therapy (DT) included patients first treated for nAMD and subsequently treated for GA (anti-VEGF/complement DT) and patients first treated for GA and subsequently treated for nAMD (anti-complement/anti-VEGF DT).

Researchers found that a total of 1.2 million intravitreal injections were administered to 47,659 patients, accounting for more than 54,000 eyes. They found that a total of 67,767 dual therapy intravitreal injections were administered, and 1.1 million monotherapy injections were given. Wood said during his presentation that Eylea was the common anti-VEGF therapy used and Empaveli was the common anti-complement therapy used.

The overall incidence of adverse inflammatory reactions was low. In both the dual therapy and monotherapy groups, there was a low rate of adverse events that were studied, including endophthalmitis (eye infection), panuveitis (widespread inflammation), retinitis (inflammation of the retina), anterior uveitis (inflammation of the iris), intermediate uveitis, posterior uveitis (inflammation at the back of the eye), unspecified uveitis, vitritis (inflammation of the vitreous), retinal detachment, and retinal vasculitis (inflammation of the blood vessels of the retina).

“In this data set, there was no significant difference in any measured safety event or change in IOP [intraocular pressure] with anti-VEGF and anti-complement dual therapy compared with monotherapy with either agent, and no significant difference between simultaneous, same-day, and subsequent separate-day dual therapy for anti-complement monotherapy,” Wood said.