[The effect of angiogenesis inhibitor therapy on the risk of fibrosis formation in neovascular age-related macular degeneration and potential strategies for its prevention].

Authors

A Zh Fursova, M A Vasilyeva, A S Derbeneva, I M Amir, M S Tarasov, I F Nikulich, Yu A Karlash, E R Agamian

Published in

Vestnik oftalmologii. Volume 142. Issue 4. Pages 120-126.

Abstract

Numerous randomized clinical trials and real-world clinical practice have demonstrated the effect of angiogenesis inhibitors (anti-VEGF agents) on the activity and growth of neovascular complexes in neovascular age-related macular degeneration (nAMD), with a proven reduction in the risk of macular fibrosis, the incidence of which decreased from 39-100% in the "pre-antiangiogenic era" to 20.4-61.4% after introduction of anti-VEGF therapy. The main factors determining the risk of subretinal fibrosis are disease activity, time of therapy initiation, treatment regimen, its regularity, and the type of drug. Variations in retinal thickness and the volatility of specific fluid compartments lead to an increase in the volume of subretinal hyperreflective material (SHRM) and prevent full restoration of the integrity of the ellipsoid zone. Extensive research into the role of angiopoietin-2 (Ang-2) in the development of fibrosis has shown that it acts not only as a cofactor of angiogenesis but also as an independent regulator of fibrogenesis through vascular destabilization with increased VEGF-mediated permeability and exudation, activation of macrophages and microglia with the production of TGF-β and CTGF, and cross-talk with classical fibrotic pathways. The synergism between Ang-2 and VEGF-A stimulates subretinal scarring and highlights the high potential of bispecific therapy for improving clinical outcomes in patients with nAMD. Compensatory activation of Ang-2 during anti-VEGF monotherapy may support tissue remodeling, contributing to the development of treatment resistance. Preclinical studies in models of choroidal neovascularization and clinical data on the effectiveness of faricimab 6 mg through dual Ang-2/VEGF-A inhibition have demonstrated not only superiority in controlling exudation and resolving retinal edema but also a targeted effect on preventing proliferation and the development of subretinal fibrosis, as confirmed by a significant reduction in the volume of SHRM - a key precursor to fibrotic changes.

PMID:
42608931
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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