Age-related macular degeneration is a progressive degeneration disease of the macula, the region of the retina responsible for central vision, which is critical for fine vision. It is one of the most common forms of blindness in the elderly. Early signs occur in 30% of all individuals 75 or older; about one quarter of these individuals have severe disease with significant visual loss. AMD is rarely found in individuals younger than 55 years. Approximately 50% of the population-attributable genetic risk is due to a polymorphic variant, Tyr402His, in the complement factor H (CFH) gene. In contrast, polymorphic variants in two other genes in the alternative complement pathway, factor B (CFB) and complement component 2 (C2), confer a significantly reduced risk of AMD.

In addition to the polymorphisms in the three complement factor genes mutations on other loci have been implicated in a small percentage of patients with AMD. In 7 of 402 patients with AMD, different heterozygous missense mutations were identified in the FBLN5 gene encoding fibulin 5, a component of the extracellular matrix involved in the assembly of elastin fibers. All patients had small circular drusen and retinal detachments. AMD was also seen among relatives of patients with Stargardt disease, an early-onset recessive form of macular degeneration seen in individuals homozygous for mutations in the ABCA4 gene. The affected relatives were heterozygous for ABCA4 mutations. Mutations at each of these loci account for only a small proportion of the large number of individuals with AMD.

The pathobiology of AMD is characterized by inflammation. The current view is that inflammatory insults characteristic of age have a greater impact in the retina of individuals predisposed to AMD because of reduced activity of the alternative complement pathway in limiting the inflammatory repsonse. The inflammation damages the photoreceptors of the macula, causing retinal atrophy. AMD is further divided into “dry” and “wet” types. Early AMD is usually dry (atrophic). Dry AMD is characterized by large, soft drusen, the clinical and pathological hallmark of AMD. Drusen are localized deposits of extracellular material behind the retina in the region of the macula