TOPLINE:

Aflibercept 8 mg administered every 12 or 16 weeks demonstrated comparable improvements in best-corrected visual acuity and central subfield retinal thickness as 2-mg dose every 8 weeks in patients with polypoidal choroidal vasculopathy (PCV).

METHODOLOGY:

• The PULSAR trial was a 96-week phase 3 randomized clinical trial evaluating aflibercept 8 mg vs 2 mg in treatment-naive patients aged 50 years or older with neovascular age-related macular degeneration.
• Researchers conducted a post hoc subgroup analysis of the PULSAR data, comparing outcomes of aflibercept 8 mg and 2 mg through week 48 in 139 participants with PCV confirmed by indocyanine green angiography.
• Participants were randomly assigned in a 1:1:1 ratio to receive aflibercept 8 mg every 12 weeks (n = 44; mean age, 72.2 years; 50% women), 8 mg every 16 weeks (n = 41; mean age, 73.2 years; 37% women), or 2 mg every 8 weeks (n = 54; mean age, 72.6 years; 31% women), following three initial monthly doses.
• The primary outcome was the change in best-corrected visual acuity from baseline at week 48, measured in Early Treatment Diabetic Retinopathy Study letters. Secondary outcomes included changes in central subfield retinal thickness and the presence of intraretinal or subretinal fluid.
• Polypoidal lesions were classified as present, absent, or questionable, with regression defined as the complete absence of lesions.

TAKEAWAY:

• Participants with PCV showed similar improvements in best-corrected visual acuity with aflibercept 8 mg every 12 weeks, 8 mg every 16 weeks, and 2 mg every 8 weeks, with least-squares mean changes of +9.5, +8.4, and +9.1 letters, respectively.
• Reductions in central subfield retinal thickness were similar across all treatment groups, with least-squares mean changes of -159, -152, and -161 μm for the 8 mg every 12 weeks, 8 mg every 16 weeks, and 2 mg every 8 weeks groups, respectively.
• At week 48, complete regression of polypoidal lesions was observed in 37% of participants receiving aflibercept 8 mg every 12 weeks, 47% of those receiving 8 mg every 16 weeks, and 38% of those receiving 2 mg every 8 weeks.
• Ocular adverse events related to treatment in the study eye were reported by 26%-39% of participants by week 48, with nonocular adverse events observed in 44%-56% of participants.

IN PRACTICE:

“[T]his PULSAR trial post hoc subgroup analysis in participants with PCV demonstrated similar visual and anatomic improvements with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting its use as an alternative monotherapy for PCV,” the researchers wrote.

“High-dose aflibercept represents a promising advancement for potentially reducing treatment burden in PCV while maintaining efficacy and safety,” an expert wrote in an invited commentary.

SOURCE:

This study was led by Won Ki Lee, MD, PhD, at the Nune Eye Hospital in Seoul, Republic of Korea, and was published online on December 18, 2025, in JAMA Ophthalmology.

LIMITATIONS:

The study’s limitations included its exploratory nature and the relatively small sample size of participants. The fixed dosing regimen for aflibercept 2 mg did not allow for comparison of extended dosing intervals.

DISCLOSURES:

The PULSAR study and the analysis were sponsored by Bayer AG and cofunded by Regeneron Pharmaceuticals Inc. Some authors reported receiving grants, personal fees, and having other ties with various companies including Bayer, Novartis, and Roche. Some authors reported being employees and/or stockholders of Bayer Consumer Care AG, Bayer AG, or Bayer Healthcare.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.