Polypoidal Choroidal Vasculopathy: From Clinicopathological and Molecular Perspectives

Abstract

<p>Background: Polypoidal choroidal vasculopathy (PCV) causes severe visual impairment in patients with neovascular age-related macular degeneration (nAMD). Currently, PCV is classified as a subtype or variant of type 1 macular neovascularization. Effective treatments for PCV remain limited, despite the variable efficacy of anti-vascular endothelial growth factor (VEGF) drugs in regressing polypoidal lesion(s) (PLs). A key contributing factor is the incomplete understanding of the disease mechanisms, which highlights the necessity for reliable animal models and a comprehensive understanding from multiple perspectives. Summary: This review elucidates the complexities of PCV through an integrated analysis of its clinical characteristics, pathological features, and molecular mechanisms. Both PLs and the branching neovascular network (BNN) are neovascular lesions located beneath the retinal pigment epithelium (RPE), as evidenced by optical coherence tomography angiography (OCTA) and clinicopathological studies. Key distinctions between PLs and BNN include lesion location, cellular component, and vascular maturity. Three-dimensional OCTA reconstruction demonstrated an anteroposterior separation between PLs and BNN, and revealed an internal microvascular architecture within PLs. Clinicopathological analysis demonstrated markedly incomplete coverage of mural cells - specifically, a lack of pericytes in PLs and relatively reduced coverage of vascular smooth muscle cells in BNN. This incomplete coverage might be attributed to increased expression of angiopoietin-2 (Ang-2), leading to mural cell loss via the integrin-mediated signaling pathway. Key Messages: Regressing PLs and promoting BNN maturity through various approaches might provide an optimal treatment strategy for PCV management. However, a comprehensive understanding of the complex mechanisms of PCV merits further investigation for better management of this refractory disease. </p>.

Keywords: Angiopoietin-2; Branching neovascular network; Mural cell; Pericyte; Polypoidal choroidal vasculopathy; Polypoidal lesion; Vascular endothelial growth factor; Vascular smooth muscle cell.