Polypoidal Choroidal Vasculopathy: From Clinicopathological and Molecular Perspectives

Area of Science:

• Ophthalmology
• Vascular Biology
• Molecular Medicine

Background:

• Polypoidal choroidal vasculopathy (PCV) is a major cause of vision impairment in neovascular age-related macular degeneration (nAMD).
• Current treatments, including anti-VEGF therapies, show variable efficacy in regressing polypoidal lesions (PLs).
• A deeper understanding of PCV's underlying mechanisms is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To elucidate the complexities of PCV by integrating clinical, pathological, and molecular data.
• To differentiate polypoidal lesions (PLs) from the branching neovascular network (BNN) in PCV.
• To explore the molecular mechanisms, including angiopoietin-2 (Ang-2) signaling, contributing to PCV pathogenesis.

Main Methods:

• Analysis of clinical characteristics and pathological features of PCV.
• Utilizing optical coherence tomography angiography (OCTA) for three-dimensional reconstruction of neovascular lesions.
• Clinicopathological examination to assess mural cell coverage and molecular markers.

Main Results:

• PLs and BNN are distinct neovascular lesions beneath the retinal pigment epithelium (RPE) with differences in location, cellular composition, and maturity.
• Three-dimensional OCTA revealed anteroposterior separation between PLs and BNN, and internal vascular architecture within PLs.
• PCV lesions exhibit incomplete mural cell coverage, particularly a lack of pericytes in PLs, potentially linked to increased Ang-2 expression and integrin signaling.

Conclusions:

• Regressing PLs and promoting BNN maturity may offer an optimal treatment approach for PCV.
• Further investigation into the complex molecular mechanisms of PCV is essential for improved management of this challenging condition.