Ocular Therapeutics and Molecular Delivery Strategies for Neovascular Age-Related Macular Degeneration (nAMD)

Int J Mol Sci. 2021 Sep 30;22(19):10594. doi: 10.3390/ijms221910594.

Abstract

Age-related macular degeneration (AMD) is the leading cause of vision loss in geriatric population. Intravitreal (IVT) injections are popular clinical option. Biologics and small molecules offer efficacy but relatively shorter half-life after intravitreal injections. To address these challenges, numerous technologies and therapies are under development. Most of these strategies aim to reduce the frequency of injections, thereby increasing patient compliance and reducing patient-associated burden. Unlike IVT frequent injections, molecular therapies such as cell therapy and gene therapy offer restoration ability hence gained a lot of traction. The recent approval of ocular gene therapy for inherited disease offers new hope in this direction. However, until such breakthrough therapies are available to the majority of patients, antibody therapeutics will be on the shelf, continuing to provide therapeutic benefits. The present review aims to highlight the status of pre-clinical and clinical studies of neovascular AMD treatment modalities including Anti-VEGF therapy, upcoming bispecific antibodies, small molecules, port delivery systems, photodynamic therapy, radiation therapy, gene therapy, cell therapy, and combination therapies.

Keywords: age-related macular degeneration; bispecific antibodies; cell therapy; gene therapy; ocular therapeutics; port delivery system.

Publication types

  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Cell- and Tissue-Based Therapy / methods*
  • Choroidal Neovascularization / drug therapy
  • Choroidal Neovascularization / radiotherapy
  • Drug Delivery Systems / methods*
  • Genetic Therapy / methods*
  • Geographic Atrophy / drug therapy*
  • Geographic Atrophy / metabolism
  • Geographic Atrophy / pathology
  • Geographic Atrophy / radiotherapy*
  • Humans
  • Intravitreal Injections
  • Photochemotherapy / methods*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / metabolism
  • Wet Macular Degeneration / pathology
  • Wet Macular Degeneration / radiotherapy*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A