High-Dose Aflibercept Effective With Extended Dosing in Polypoidal Choroidal Vasculopathy: PULSAR Analysis
South Korea: In a post hoc analysis of the randomized PULSAR trial, aflibercept 8 mg demonstrated noninferior visual outcomes compared with the standard 2-mg dose in patients with polypoidal choroidal vasculopathy (PCV), a subtype of neovascular (“wet”) age-related macular degeneration.
The higher dose allowed for longer treatment intervals while maintaining similar vision gains. Polypoidal choroidal vasculopathy, which is more prevalent in Asian populations and associated with greater retinal fluid and hemorrhage, carries a higher risk of vision loss, highlighting the potential benefit of less frequent high-dose therapy.
PCV is a distinct form of neovascular age-related macular degeneration characterized by abnormal branching vascular networks and polyp-like lesions beneath the retina. These features often lead to recurrent bleeding and fluid accumulation, resulting in poorer visual prognosis compared with typical neovascular AMD. Although anti–vascular endothelial growth factor (VEGF) agents are widely used, treatment burden remains a challenge, particularly in patients requiring frequent injections to maintain disease control.
The findings, published in JAMA Ophthalmology, are based on a post hoc subgroup analysis of the phase 3 PULSAR randomized clinical trial conducted across hospitals and clinics in 12 countries. Investigators evaluated adults with neovascular AMD who had indocyanine green angiography–confirmed PCV. The analysis included 139 participants whose data were collected between August 2020 and July 2022.
Participants were randomly assigned in a 1:1:1 ratio to receive aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or aflibercept 2 mg every 8 weeks, following three initial monthly loading doses. For patients in the high-dose arms, dosing intervals could be shortened from week 16 onward if predefined disease activity criteria were met at scheduled visits. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to week 48.
The study led to the following findings:
- Among 139 participants, 44 received aflibercept 8 mg every 12 weeks, 41 received 8 mg every 16 weeks, and 54 received aflibercept 2 mg every 8 weeks.
- The mean age across treatment groups was approximately 72–73 years, with broadly comparable baseline visual acuity.
- At week 48, improvements in best-corrected visual acuity were similar across all groups, with gains of 9.5 letters in the 8-mg every-12-week group, 8.4 letters in the 8-mg every-16-week group, and 9.1 letters in the 2-mg every-8-week group.
- Visual outcomes met noninferiority criteria for aflibercept 8 mg compared with the standard 2-mg regimen.
- Nearly 90% of patients treated with aflibercept 8 mg maintained extended dosing intervals of 12 weeks or longer.
- Anatomic outcomes were comparable, with polypoidal lesions absent at week 48 in approximately one-third to nearly half of participants across treatment arms.
- The safety profile of aflibercept 8 mg was similar to that of the 2-mg dose, with no new safety signals identified.
The authors noted that the exploratory post hoc design and small sample size were key limitations, and the fixed 8-week regimen in the 2-mg group precluded evaluation of longer dosing intervals. Despite this, aflibercept 8 mg monotherapy appeared to be an effective PCV option, enabling fewer injections while maintaining visual and anatomic outcomes.
"Overall, the findings support the potential role of high-dose aflibercept in addressing the unmet need for durable, practical treatment strategies in PCV, particularly in populations at higher risk of vision loss," the authors concluded.
Reference:
Lee WK, Wong TY, Chen S, et al. Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: Post Hoc Analysis of the PULSAR Randomized Clinical Trial. JAMA Ophthalmol. Published online December 18, 2025. doi:10.1001/jamaophthalmol.2025.5098
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