Comparative efficacy of photodynamic therapy (PDT), ranibizumab, aflibercept monotherapy, and combination therapies for polypoidal choroidal vasculopathy: a network meta-analysis of randomized controlled trials

Polypoidal choroidal vasculopathy (PCV) is recognized as a distinct clinical condition characterized by persistent serous leakage, bleeding, and the presence of polypoidal lesions beneath the retinal pigment epithelium (RPE). This systematic review and meta-analysis aimed to evaluate the effectiveness of combination treatments that include antivascular endothelial growth factor (anti-VEGF) agents, such as ranibizumab and aflibercept, along with photodynamic therapy (PDT), in comparison to monotherapy options for managing PCV. A comprehensive literature search was performed in PubMed, Web of Science, and the Cochrane Library, following the PRISMA guidelines. Eligible studies consisted of treatment-naïve patients with PCV receiving anti-VEGF monotherapy, PDT monotherapy, or combination therapies. The key outcomes analyzed included changes in best-corrected visual acuity (BCVA), reduction in central subfield thickness (CSFT), rate of polyp regression, incidence of adverse events, and treatment burden. Statistical analyses were conducted via a random-effects model, and heterogeneity was assessed via the I² statistic. Fourteen randomized controlled trials (RCTs) involving 1,426 eyes were included. Compared with monotherapies, combination therapies, especially anti-VEGF in conjunction with PDT, showed superior efficacy in improving the BCVA (mean difference [MD] = 0.07, 95% CI: 0.06-0.08) and reducing the CSFT (MD = -42.09 μm, 95% CI: -59.93 -24.24). The regression rates of polyps were highest in the combination groups, with up to 77.8% achieving complete regression, and fewer anti-VEGF injections were required than monotherapies. Adverse event rates, such as subretinal hemorrhage, remained low across all treatment groups. Compared with monotherapy, combination therapies using anti-VEGF agents and PDT provide significant visual and anatomical advantages in managing PCV. These treatments are associated with improved efficacy and a reduced treatment burden while maintaining favorable safety profiles. However, further standardization of protocols and evaluation of long-term cost-effectiveness are crucial for improving clinical practice applications. Retrospectively registered.