Age-related macular degeneration (AMD) is the third leading cause of vision loss worldwide and the most common form of legal blindness in the elderly. 1 Millions of individuals who are older than 50 years in Europe and North America have AMD, and it is estimated that more than 300,000 new cases are diagnosed annually. 2, 3 During aging, focal deposits of debris can accumulate below the retinal pigment epithelium (RPE) that are recognized in an eye examination as drusen. Clinicians have long recognized that drusen in the macula are early stages in the AMD disease process. Drusen in the macula and the size and area covered by these deposits are considered risk indicators for later development of the blinding end-stage forms of AMD. 4–6 Geographic atrophy is the end-stage of the dry form, characterized by the slow, progressive loss of the RPE. 7 Photoreceptor function is lost in regions subtended by RPE atrophy. When geographic atrophy involves the RPE below the fovea, foveal photoreceptors lose function and degenerate, causing foveal blindness. Choroidal neovascularization characterizes the wet form of AMD. When new blood vessels growing from the choroid break through Bruch’s membrane and the RPE, they can hemorrhage, causing a pool of blood to accumulate between the RPE and foveal photoreceptors resulting in acute loss of vision. 4, 5

Initial studies on AMD by my colleagues and myself focused on understanding the composition and distribution of drusen proteins. 8–13 More than 120 different proteins were identified in isolated drusen. Several laboratories have made significant contributions to the understanding of drusen composition in recent years, and a consistent finding is that many complement pathway proteins are present in drusen, suggesting that inflammation is a part of the AMD disease process. 9, 14–18 Epidemiologic studies of elderly twins pointed to the likelihood that genetic factors have a role in AMD. 19–22 Recent reports indicate that mutations/polymorphisms in genes coding for the alternative complement pathway regulator (factor H and factor H-related proteins) and complement pathway proteins (complement component C2, C3, and factor B) are present in more than 50% of patients with AMD. Collectively, these studies strongly indicate that AMD has a genetic component and that inflammation plays an important role in the pathology of AMD. 23–32