Classification and Epidemiology
Early AMD is characterised by drusen ≥63 μm diameter and hyper- or hypo-pigmentation. A proportion of eyes with early AMD progress to late AMD, that is, exudative AMD or geographic atrophy (GA). In exudative AMD, also termed neovascular AMD (nvAMD), new blood vessels develop which in the vast majority of cases have their origin in the choroid, which subsequently invade the retina (choroidal neovascularisation, CNV). In some cases, the vessels may arise in the retina, retinal angiomatous proliferation (RAP), before anastomosing with choroidal vessels. In other cases, the vascular abnormality may be contained within the choroid: idiopathic polypoidal choroidopathy (IPC). Regardless of the origin and/or the location of the neovascular complex, the vessels are abnormal and allow blood constituents to leak out, causing anatomical disruption, cell loss and eventually fibrosis. GA is a sharply demarcated area of partial or complete depigmentation reflecting atrophy of the retinal pigment epithelium.
A number of classification systems exist but often these have limited applicability in clinical settings. The pragmatic 4-stage grading system validated in the Age-Related Eye Disease Study (AREDS) is therefore advocated. Three ocular factors predict the progression of AMD: the presence of large drusen (>125 μm, which approximates the size of a normal retinal vein at the disc margin), retinal pigment epithelial abnormalities, and the presence of late AMD in one eye.
In the United Kingdom, the prevalence of late AMD has been estimated as 4.8% (95% CI 3.4–6.6%) in those over 65 years and 12.2% (95% CI 8.8–16.3%) in those aged 80 years or more. In the United Kingdom, an estimated quarter of a million adults suffer blindness due to this condition.
The natural history of advanced AMD is one of unremitting central visual loss. A longitudinal study of GA found that 31% suffered a three-line loss in acuity within 2 years of diagnosis and that this had increased to 53% at 4 years. A meta-analysis of high-quality trials on nvAMD for which data were available on natural history found that the proportion of patients who developed severe vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% at 3 years. Vision-related quality of life has been shown to decline significantly as early AMD progresses to late AMD over a 15-year follow-up.