Detailed clinical phenotyping in Age-related Macular Degeneration
Age-related Macular Degeneration (AMD) is a degenerative disorder that accounts for about 50% of blindness in England and Wales. At present there is no effective treatment. It occurs in genetically susceptible individuals exposed to environmental factors such as smoking but so far specific factors remain to be identified. For this descriptive study, 879 patients with Age-Related Maculopathy (ARM) and AMD and 44 spouses with normal maculae, to act as a comparison group, were recruited from a tertiary referral centre. The clinical phenotypes were analysed from fundus photographs, fluorescein angiography and autofluorescence (AF) images. Fundus features were characterised as they are thought to reflect the genes conferring risk in an individual and may allow greater understanding of disease mechanisms. These data demonstrated (1) A revised grading system shown to be reproducible for use with digital images (2) A moderate concordance rate for phenotype between eyes with end- stage AMD (kappa statistic=0.48 95% CI = 0.38-0.57, p0.001). (3) Distinct characteristics, including a larger area and higher counts of soft drusen with focal areas of increased AF, in fellow eyes of those with unilateral visual loss due to geographic atrophy (GA). (4) An increased susceptibility of the inferotemporal macula to GA. (5) Preserved integrity of the retinal pigment epithelium (RPE) in the initial stages of CNV development as identified from AF images. (6) Loss of scotopic rather than photopic function over areas of increased AF, as determined by fine matrix mapping, indicating the preferential vulnerability of rods. (7) No difference in smoking history between those with neovascular compared to non-neovascular AMD. Although AMD has been extensively investigated, this study extends our knowledge of retinal AF, the relative susceptibility of rods compared to cones at the macula and suggests both eyes of an individual are more discordant for late stages of AMD compared to drusen.