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AMD Overview
Age-related Macular Degeneration (AMD) is a disease characterized by progressive degenerative abnormalities in the macula of the eye, a small area in the central portion of the retina. AMD is characteristically a disease occurring in patients older than 50 years of age and has long been recognized as the leading cause of severe and irreversible loss of central vision in adults over the age of 50 in the U.S. and other developed countries around the world [1 ,2 ]. AMD is exceptionally common, currently affecting about 8 million Americans and an additional 8 million Europeans. [3 ]. It is estimated that approximately 6% of individuals 65-74 years of age, and 20% of those older than 75 years of age are affected with AMD in the U.S. [4 ]. Because of the increasing life expectancy in developed and developing countries, the elderly sector of the general population is expected to increase at the greatest rate in the coming decades. Using U.S. Census Bureau projections, the number of Americans over 65 years of age will more than double to 80 million by the middle of this century [5 ]. In the absence of adequate prevention or treatment measures, the number of cases of AMD with visual loss is expected to grow accordingly. In addition to advanced age, there are environmental and genetic risk factors for AMD including ocular pigmentation, dietary factors, a positive family history for AMD, high blood pressure, and smoking [6 ]. Recent work has also identified inflammatory and more specific genetic contributions to the disease [7 ]. Age-related macular degeneration is classified into one of two general subgroups: the non-neovascular (non-exudative) form of the disease or ‘dry’ AMD and the neovascular (exudative) form of the disease or ‘wet’ AMD.
Current TherapyFDA-approved therapies for neovascular AMD consist of thermal laser photocoagulation, photodynamic therapy with Visudyne (PDT), and anti-vascular endothelial growth factor (anti-VEGF) therapy (Lucentis® and Macugen® intravitreous injections). Thermal laser, in which the blood vessels under the sub-retinal space are destroyed, is employed most often for extrafoveal lesions (lesions outside of the fovea), but not subfoveal lesions (lesions under the fovea, the center most part of the macula which provides for our central, sharpest vision), and thus is considered for only 10% to 15% of all cases of neovascular AMD. Moreover, laser treatment of neovascular AMD is associated with a one-year recurrence rate that exceeds 50%. PDT is approved for the treatment of patients with only one type of wet AMD (the predominantly classic subtype of lesion [10 ]), which make up only 25% of the total patient population with wet AMD; PDT is a moderately effective treatment at best. Lucentis® (ranibizumab, an antibody) and Macugen® (pegaptanib sodium, an aptamer) are anti-VEGF agents which are used to treat neovascular AMD. These anti-VEGF agents can prevent the continuous deterioration of visual acuity that is associated with this disease by halting new vessel formation and decreasing vascular leakage. Thus Lucentis® and Macugen®, which address the underlying cause of AMD, are considered as first-line therapies for neovascular AMD. Lucentis® is the most commonly used FDA-approved therapy for wet AMD, and can provide significant visual gain in approximately one-third of patients. Avastin® (bevacizumab) is a recombinant humanized monoclonal IgG1 antibody (of which Lucentis® is an antibody fragment), and is approved for intravenous use in colorectal and lung cancer. In off-label use, Avastin administered in the eye by intravitreal injection has been frequently used by clinicians to treat wet AMD. AMD remains an area of significant medical need and is a major public health issue in a fast-growing elderly population. There are substantial opportunities for the development and commercialization of novel therapies to improve the treatment of AMD.
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