Management of Neovascular AMD

Key Points

•VEGF is the most important regulator of angiogenesis and a potent promoter of vascular permeability in different ocular diseases, including AMD. For this reason, VEGF is a key target in treating ocular neovascularization.

•Two anti-VEGF agents have achieved regulatory approval, with others in clinical trials.

•Clinical trials have shown that intravitreal ranibizumab is safe drug and effective, being the first agent to promote visual acuity improvement in patients with wet AMD.

•Bevacizumab, a monoclonal antibody against VEGF, was approved for intravenous, systemic therapy for different types of cancer. It has been used off-label as an intravitreal injection in wet AMD since 2005 with clinical results similar to ranibizumab.

•CATT head-to-head trial comparing bevacizumab versus ranibizumab demonstrated that they have similar outcomes when the same treatment regimen is applied.

F.M. Penha(*)

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, 900 NW 17 St., Miami, FL 33136, USA

e-mail: fpenha@med.miami.eduf; penha@me.com

•New promising anti-VEGF drugs (VEGFTrap, KH902, and Pazopanib) are in ongoing clinical trials.

Introduction

Exudative eye diseases, including neovascular age-related macular degeneration (AMD), diabetic retinopathy with macular edema (DME), and retinal vein occlusion (RVO), are the primary causes of clinically significant vision loss in the developed world, particularly among the working and elderly populations [1–3]. In the United States, neovascular AMD is the leading cause of irreversible blindness among those over the age of 65, affecting at least 1.75 million individuals [4]. The neovascular form of AMD is responsible for most of the severe vision loss associated with the diseases. Neovascular AMD arises from the nonexudative form of AMD and is characterized by the growth of abnormal blood vessels in the macula, which arise either from the choroidal circulation and penetrate through Bruch’s membrane (known as choroidal neovascularization (CNV)) or arise primarily from the retinal circulation (known as retinal angiomatous proliferation (RAP)). Both forms of neovascularization cause disruption of the normal outer retinal and inner choroidal anatomy resulting from fibrovascular proliferation and the accumulation of fluid in the subretinal pigmented epithelium (sub-RPE) space, the subretinal space, and within the retina [5, 6].