Natural History of Predominantly Classic, Minimally Classic, and Occult Subgroups in Exudative Age-related Macular Degeneration

Abstract

We previously showed that the pattern of vision loss in eyes with subfoveal neovascularization in age-related macular degeneration (AMD) is uniform across a wide range of clinical trials, with apparent differences arising from differences in the time of entry of patients into clinical trials. In the current study, we used a similar analysis to compare the visual loss of untreated control eyes classified as predominantly classic (PC), minimally classic (MC), and occult with no classic (occult) based on fluorescein angiography. Meta-analysis of prior clinical trials. Data from patients enrolled in the Macular Photocoagulation Study (MPS), Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study, Verteporfin in Photodynamic Therapy (VIP) Study, Anecortave Acetate (AA) Trial, VEGF Inhibition Study in Ocular Neovascularization (VISION), and Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA) Trials. Visual acuity (VA) data of untreated control eyes for each study from appropriate subgroups were plotted on a double reciprocal (Lineweaver-Burke) plot of 1/[letters lost] versus 1/[months]. To correct for differences in time of entry into clinical trials, we introduced a horizontal translation factor to shift each data subset. We determined the coefficient of determination before and after adjustments for visual acuity at the time of enrollment. On a Lineweaver-Burke plot, the cumulative subgroups had an overall coefficient of determination of only r(2)<0.01 for the raw data but improved to a remarkably high r(2) = 0.90 when data were corrected for time of entry into clinical trials. For each subgroup there was excellent correlation between 1/[letters lost] versus 1/[months of exudative disease] for PC (r(2) = 0.91), MC (r(2) = 0.95), and occult (r(2) = 0.98) choroidal neovascularization. We were able to demonstrate a strong correlation for visual acuity as a function of time that is independent of the fluorescein angiography classification of a lesion, suggesting that initial protocol visual acuity, rather than angiographic classification, is the major determinant of the behavior of visual acuity as a function of time in exudative AMD.