Anti-VEGF Compounds in the Treatment of Neovascular Age Related Macular Degeneration

C.      Campa; S.      P. Harding

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly patients in developed countries. Although the pathogenesis of AMD is still largely unknown, it is now well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels (i.e. choroidal neovascularization, CNV) which characterizes the “wet form” of this ocular disease. Therefore, inhibiting VEGF has turned out to be a good way of more effectively controlling neovascular AMD. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Currently two anti-VEGF compounds have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD: pegaptanib and ranibizumab. Off-label usage of bevacizumab, an anti-VEGF agent similar to ranibizumab, has also become fairly common. The substantial improvement of visual acuity noticed in patients treated with ranibizumab has made this drug the gold standard for AMD therapy. However, as with many new therapies, there are unresolved issues, including safety, cost, and dosing frequency. This review describes in details the properties and efficacy of the three anti-VEGF agents in use in clinical practice. Promising emerging anti-VEGF strategies (VEGF-trap, small interfering RNA, tyrosine kinase inhibitors) which aim to improve outcomes, safety and treatment burden through novel mechanisms of action are also discussed.

Keywords: Vascular endothelial growth factor, age related macular degeneration, choroidal neovascularization, ranibizumab, bevacizumab, pegaptanib, VEGD-trap, small interfering RNA, tyrosine kinase inhibitors, heparin-binding glycoprotein, potent angiogenic, mitogenic, endothelial cells, proteoglycans, plasmin, matrix metalloproteinases (MMPs), monocytes, dummy/decoy receptor, tyrosine kinase, signal transduction, choriocapillaris, Pegaptanib Sodium, pegylated oligonucleotide aptamer, visual acuity (VA), Intravitreal Lucentis, Endophthalmitis, retinal haemorrhage, conjunctival haemorrhage, nasopharyngitis, hypertension, bronchitis, VEGF-Trap, Bevasiranib