Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration

Many diseases of ageing characterised by complex inheritance patterns are progressive; the individual may be asymptomatic in the early stages. One of these diseases, age-related macular degeneration (AMD), is the most common cause of visual impairment and the leading cause of blindness in the elderly population in the developed world. The prevalence of AMD increases with advancing age in all populations studied. Thus, in developed nations such as the USA, UK, Canada and Australia, with increasingly aged populations, the condition affects a progressively larger segment of the population and has become a major public health issue. Early- or late-stage AMD is present in 15 per cent of individuals over the age of 60 years [1]. It is estimated that there are currently 9.1 million patients in the USA with AMD, of which 1.7 million suffer with the vision-threatening late-stage complications of choroidal neovascularisation (CNV) or geographic atrophy [1]. Moreover, it is predicted that the number of cases of early AMD will increase to 17.8 million by 2050 and, if untreated, cases of late-stage blinding AMD will increase to 3.8 million [1]. It has been determined that vision loss from AMD decreases quality of life by 60 per cent, similar to the experience of dealing with a stroke that requires intensive nursing care [2].The clinical presentation and natural course of AMD are highly variable. The disease may present as early as the fifth decade of life or as late as the ninth decade. The clinical symptoms of AMD range from no visual disturbances in early disease to profound loss of central vision in the advanced late stages of the disease. Some patients never progress beyond early AMD; however, in 10-15 per cent of Caucasian patients with early-stage disease, the condition progresses to an exudative neovascular (or 'wet' form) or geographic atrophic (or 'dry' form) AMD, which threatens vision. The phenotype is characterised by development of subretinal choroidal neovascular c