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Review
. 2023 Feb 21;21(1):133.
doi: 10.1186/s12967-023-03937-7.

Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration

Levon M Khachigian  1 , Gerald Liew  2 , Kelvin Y C Teo  3   4 , Tien Y Wong  3   4   5 , Paul Mitchell  2
Affiliations
Review

Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration

Levon M Khachigian et al. J Transl Med. .

Abstract

Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.

Keywords: Aflibercept; Anti-VEGF therapy; Bevacizumab; Brolucizumab; Faricimab; Neovascular age-related macular degeneration; Ranibizumab; VEGF receptors; Vascular endothelial growth factor.

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Conflict of interest statement

LMK has IP interests in BT2. GL has consulted for Bayer and Novartis and has received travel grants and research funding from Bayer. KYCT reports consultancy fees, honorarium, travel support and speaker fees from Topcon, Roche, Bayer and Novartis outside the submitted work. TYW is a consultant for Bayer, Boehringer-Ingelheim, Eden Ophthalmic, Genentech, Iveric Bio, Merck, Novartis, Oxurion, Roche, Samsung, Shanghai Henlius and Zhaoke Pharmaceutical. He is an inventor, holds patents and is a co-founder of start-up companies (Plano and EyRiS), which have interests in, and develop digital solutions for eye diseases. All potential conflicts of interests for consultancy, advisory boards and positions in the start-up companies, and financial renumeration, if any, are managed by institutional policies under SingHealth and Duke-NUS Medical School. PM has consulted for Bayer, Novartis, and Allergan.

Figures

Fig. 1
Fig. 1
VEGF ligands and receptors. The VEGF ligand family (comprising VEGF-A, VEGF-B, VEGF-C, VEGF-D, virally encoded VEGF-E and placental growth factor (PlGF)) interacts selectively with 3 cell surface receptors (VEGFR1, VEGFR2, VEGFR3). Currently approved therapies are indicated in black font. Examples of emerging or experimental therapies are shown in blue font. Refer to text for detail
See this image and copyright information in PMC

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