Clinical Outcomes of High-Dose Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: A Systematic Review and...

Polypoidal choroidal vasculopathy (PCV) is a distinct subtype of neovascular macular disease with variable responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. This systematic review and meta-analysis evaluated the visual, anatomical, and lesion-regression outcomes of intravitreal aflibercept 8 mg, a formulation developed to extend dosing intervals while maintaining efficacy, in patients with PCV. PubMed, Embase, Scopus, Web of Science, and Google Scholar were searched from inception to March 12, 2026 (PROSPERO: CRD420261339679). Eligible studies enrolled adults with indocyanine green angiography (ICGA)-confirmed PCV treated with aflibercept 8 mg and reported at least one co-primary outcome: change in best-corrected visual acuity (BCVA), central retinal or subfield thickness (CRT/CST), or complete polyp regression. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2), Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and Joanna Briggs Institute (JBI) appraisal tools. Complete polyp regression was analyzed using a generalized linear mixed model with a logit link; continuous outcomes were pooled using restricted maximum likelihood estimation with the Hartung-Knapp-Sidik-Jonkman correction. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Five studies encompassing 362 eyes (245 treated with aflibercept 8 mg) were included. The pooled complete polyp regression rate was 57% (95% confidence interval (CI), 39%-73%; I²=55.9%; k=3). The pooled mean CRT/CST change was -157.8 µm (95% CI, -176.9 to -138.7 µm; I²=0%; k=2), though the estimate was predominantly driven by a single study contributing 95.5% of the inverse-variance weight. BCVA outcomes were not pooled due to metric incompatibility and clinical heterogeneity; however, individual study results were directionally favorable, with Early Treatment Diabetic Retinopathy Study (ETDRS) gains of +8.4 to +9.5 letters at 48 weeks in the largest contributing study. Extended dosing intervals were maintained in 80.5% (q12) and 86.5% (q16) of treated eyes at 48 weeks. One study reported intraocular inflammation in 10.8% of the overall neovascular age-related macular degeneration (AMD) cohort in that study, a safety signal not observed in the remaining studies. The certainty of evidence was low for CRT/CST change and very low for polyp regression and BCVA. Available evidence suggests that aflibercept 8 mg may produce clinically relevant polyp regression and substantial anatomical improvement in PCV, with a potential reduction in injection frequency. However, given the low to very low certainty of the current evidence base across all co-primary outcomes, definitive efficacy and safety conclusions cannot yet be drawn. Prospective, PCV-specific trials with standardized outcome reporting are needed.