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To compare changes in optical coherence tomography angiography in eyes with polypoidal choroidal vasculopathy after treatment with anti–vascular endothelial growth factor monotherapy or combined with photodynamic therapy.This is a longitudinal case-controlled study. The authors performed optical coherence tomography angiography at baseline and Month 3 in patients with treatment-naive polypoidal choroidal vasculopathy undergoing monotherapy (n = 10) or combination therapy (n = 13). We analyzed flow signal within the outer retina and choriocapillaris using automated segmentation. The authors analyzed the presence of pachyvessels using a 10.4-μm segment through Haller layer. The changes in each layer were compared between treatments.At Month 3, both groups showed similar improvement in best-corrected visual acuity and central retinal thickness. However, flow signal within the polypoidal choroidal vasculopathy complex was decreased in more eyes after combination therapy than after monotherapy (84.6% vs. 40.0%, P = 0.04). Patchy reduction in flow signal within the choriocapillaris layer was noted in 15.4% and 10.0% after combination therapy and monotherapy, respectively (P = 0.61). Significant reduction in pachyvessel caliber was seen only after combination therapy but not after monotherapy (75.0% vs. 0.0%, P = 0.01).Longitudinal optical coherence tomography angiography demonstrates more significant reduction in lesion flow and pachyvessels in the short term after combination therapy than after monotherapy, although visual and structural OCT showed similar improvement.