Patients with neovascular age-related macular degeneration who have not had treatment before for their disease had measurable improvements in visual acuity and key anatomical markers after 6 months of treatment with high-dose aflibercept, the first global, real-world study of the drug showed.

“These month-6 results from SPECTRUM support the real-world effectiveness and safety of aflibercept 8 mg in patients with treatment-naive neovascular age-related macular degeneration,” Clare Bailey, MD, a retina specialist at the University Hospitals Bristol and Weston NHS Foundation Trust in Bristol, England, reported at the European Society of Retina Specialists (EURETINA) 2025, Congress in Paris, France.

Aflibercept 8 mg, a VEGF inhibitor approved by the FDA in 2023 for the treatment of retinal diseases, is a newer iteration of aflibercept 2 mg, which the agency first approved in 2011.

Bailey presented data on the first 150 treatment-naive patients enrolled in the SPECTRUM study. So far, the trial has enrolled 3463 patients with neovascular age-related macular degeneration, including more than 1100 who have had no previous treatment for their disease.

The 150 patients had an average improvement of 3.5 ETDRS letters after 6 months, along with a reduction of 190 μm in central retinal thickness, a key marker of retinal inflammation, Bailey said. A 3.5 ETDRS letter improvement can be the difference between 20/40 and 20/35 vision on the Snellen chart.

Worst Measures, Most Improvement

Patients with worse vision experienced more robust improvements in eyesight, Bailey said. Those with visual acuity of 20/200 Snellen, or 35 ETDRS letters, or worse — the definition of legal blindness — averaged an improvement of 14.3 letters at 6 months, improving close to 20/100 Snellen. Patients with visual acuity of 35-69 letters, ranging from 20/200 to 20/40 Snellen, gained 4.9 letters. In patients with 20/40 vision or better, the improvement was less robust, averaging 0.7 ETDRS letters, which is an incremental change in Snellen vision.

Patients with worse central retinal thickness also had more robust improvements after 6 months of treatment with aflibercept 8 mg, Bailey said. Those with central retinal thickness < 400 μm upon enrollment in the trial averaged a 64-μm reduction at 6 months; patients with central retinal thickness > 400 μm had an average reduction of 284 μm. The latter group had worse average overall central retinal thickness at 6 months: 536 vs 305 μm, she reported.

The study evaluated two anatomical markers of drug effectiveness: fluid underneath within the retina. In these 150 patients, 20.3% had no subretinal fluid upon enrollment, and 73.3% had achieved that outcome after 6 months of treatment; 44.7% had no intraretinal fluid upon study entry, with 68.4% meeting that measure at 6 months, Bailey said.

The real-world study raised no new concerns about drug safety, she said.

The patients averaged 4.7 injections of aflibercept over the 6-month trial, including an injection at their last visit and three initial monthly doses, Bailey said. After the first three monthly doses, the prescribing information recommends follow-up injections every 8-16 weeks. Bailey said the injection at the last visit would not have altered the 6-month results she presented.

“There were good anatomical improvements, and the visual acuity gains were very encouraging,” Bailey told Medscape Medical News. “We will await the 12-month data with interest as well as the further precise information about the mean number of injections prior to the last visit.”

The outcome of around 70% of eyes having no retinal fluid after 6 months of treatment “is expected,” Gabriel Katz, MD, a retina specialist at Tel Aviv University in Tel Aviv, Israel, said. However, he questioned the clinical practicality of using aflibercept 8 mg as a first-line treatment for neovascular age-related macular degeneration.

“First, some countries require the use of bevacizumab as the first line for treatment-naive patients,” he told Medscape Medical News. “Secondly, prior to the introduction of aflibercept 8 mg, the 2-mg version was the most widely preferred drug.”

Many physicians had concerns about intraocular inflammation in high-dose drugs, which was seen in previous studies with abicipar and brolucizumab, Katz said. “Therefore, aflibercept 8 mg was accepted by many physicians with some restraint,” he said. “It is nice to see real-life studies with aflibercept 8 mg do not show a significant signal of intraocular inflammation.”

The study was funded by Bayer. Bailey reported having financial relationships with Bayer, Apellis, and Roche. Katz reported having no relevant financial conflicts of interest.

Richard Mark Kirkner is a medical journalist based in Philadelphia.