Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The identification of the central role of vascular endothelial growth factor (VEGF) in the pathogenesis of neovascular AMD and the introduction of anti-VEGF agents as gold-standard treatment, have drastically changed its prognosis-something yet to be seen in dry AMD. Several therapeutic avenues with a wide variability of targets are currently being investigated in dry AMD. The approaches being investigated to reduce the rate of disease progression include, (1) drugs with antioxidative properties, (2) inhibitors of the complement cascade, (3) neuroprotective agents, (4) visual cycle inhibitors, (5) gene therapy and (6) cell-based therapies. A number of early phase clinical trials have provided promising results, with many more ongoing and anticipated in the near future. In this review, we aim to provide an update of the interventional trials to date and future prospects for the treatment of dry AMD.

Keywords: angiogenesis; degeneration; genetics; macula; retina.

Figure 1

Graphical representation of the complement cascade. The location where different therapeutics act is highlighted. The therapies are shown, with them all have a downregulating effect on the particular step, negatively impacting on the downstream pathway. This figure has been created by the authors. C, complement; IgG, immunoglobulin G; MAC, membrane attack complex.