Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues

  • Eye (Lond). 2025 Jan;39(1):40-44. doi: 10.1038/s41433-024-03373-x.
Jonathan D Shirian  1  2 ,  Priya Shukla  1  2  3 ,  Rishi P Singh  4  5  6  7
Affiliations
  • 1. Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • 2. Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
  • 3. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
  • 4. Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA. [email protected].
  • 5. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. [email protected].
  • 6. Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. [email protected].
  • 7. Cleveland Clinic Martin Health, Cleveland Clinic Florida, Stuart, FL, USA. [email protected].
PMID: 39379521 DOI: 10.1038/s41433-024-03373-x
Abstract

Neovascular age-related macular degeneration (nAMD) can lead to significant vision impairment through the growth of abnormal neovascular membranes in the choroid. Despite advancements with current anti-vascular endothelial growth factor (VEGF) therapies, challenges such as frequent injections, inadequate response, and patient-related concerns persist. Emerging therapeutics aim to reduce vision-loss through a variety of mechanisms. Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and ANG-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951.

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