The Clinical Significance of Polypoidal Lesion Regression in Polypoidal Choroidal Vasculopathy – A Review

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is a distinct pachychoroid disease in which persistent polypoidal lesions represent an important structural substrate for recurrence and hemorrhage. While standard anti-vascular endothelial growth factor (anti-VEGF) monotherapy effectively manages exudation, it often fails to achieve complete anatomical closure - a phenomenon termed the "PCV paradox." This review evaluates the prognostic significance of complete polypoidal lesion regression and synthesizes evidence on the efficacy of various therapeutic strategies in achieving durable anatomical clearance. OBSERVATIONS: Multimodal imaging, led by indocyanine green angiography (ICGA) as the reference standard, has refined PCV diagnostic criteria and nomenclature. Evidence from landmark trials demonstrates that combination therapy (anti-VEGF plus photodynamic therapy) achieves significantly higher complete polypoidal lesion regression rates (up to 77.8%) and lower injection burdens compared to monotherapy. Although newer agents such as faricimab and high-dose aflibercept show improved anatomical outcomes, complete regression can now be meaningful even with monotherapy, though it remains one of several key treatment endpoints. Persistent lesions may nonetheless act as a structural reservoir associated with recurrence and severe hemorrhagic complications. CONCLUSIONS AND RELEVANCE: Achieving complete polypoidal lesion regression is a critical clinical endpoint for ensuring long-term disease stability and reducing the risk of catastrophic recurrence. It should nonetheless be regarded as one of several important endpoints - alongside visual acuity, exudative control, safety, and treatment accessibility. Rather than being universally superior, PDT-based combination therapy is best applied selectively in centers with access to ICGA and PDT, whereas optimized treat-and-extend anti-VEGF regimens and newer agents can also achieve meaningful regression and durable functional outcomes.