Subfoveal exudative age-related macular degeneration: evidence for preoccult disease

A careful analysis of randomized clinical trials on exudative age-related macular degeneration reveals apparent differences in behavior of untreated control eyes among these trials. A priori there are two possible explanations: each study contains a unique subpopulation of patients; or apparent differences arise from differences in time of entry of these eyes into clinical trials.

To correctly account for differences in time of entry into clinical trials, we introduced a horizontal translation factor, expressed in months, to shift each data subset horizontally to maximize r2 for the cumulative trend line; this increases the overall r2 to 0.95, demonstrating that most of the variation in visual acuity over time is explained by the initial visual acuity. This analysis also suggests that occult disease is an earlier stage than minimally classic and predominantly classic disease and that there is a subclinical stage of subfoveal exudation ('preoccult') for patients with age-related macular degeneration.

The pattern of vision loss experienced in age-related macular degeneration eyes with subfoveal choroidal neovascularization is uniform across a wide range of clinical trials, with apparent differences in initial and final visual acuity in untreated eyes arising from differences in the time of entry into clinical trials. Our data suggest that visual loss may occur during a preoccult phase of choroidal neovascularization, prior to the development of occult disease.