New molecular targets for the treatment of neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive chronic disease that currently represents the leading cause of irreversible vision loss in the western world. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor A (VEGF-A) plays an important role in promoting the choroidal neovascularization that characterizes the wet form of AMD. Intravitreal injection of anti- VEGF-A agents is the current treatment of choice for neovascular AMD (nAMD). These agents have brought about dramatic changes in the treatment of nAMD, but most patients require frequently repeated injections and regular long-term follow-up, with a significant percentage of them showing resistance to anti-VEGF-A drugs. Thus, the identification of additional therapies that could improve the treatment protocols is needed. There are numerous areas of investigation into new treatments, with increasing efforts being made to study drugs that address various targets along the angiogenic signaling cascade, or other pathways related to the onset of nAMD. The aim of the present review is to summarize and discuss promising new therapies and targets that have the potential to improve outcomes and to lengthen treatment durability, especially in patients with recalcitrant or recurrent forms of nAMD.