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William J. Feuer, Philip J. Rosenfeld, Giovanni Gregori, Zohar Yehoshua, Fernando M. Penha, Emily Y. Chew, Frederick L. Ferris, III, Traci E. Clemons, Anne S. Lindblad; Square Root Transformation Of Geographic Atrophy (GA) Measurements Removes Dependence Of 4 Year Growth On Initial GA Area : A Reanalysis Of Data From AREDS Report 26. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1657.
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Previously, the growth of GA over 4 years was shown to depend on baseline lesion size (AREDS Report 26). We reassessed this dependence by performing a square root transformation of the area measurements as reported by Yehoshua et al. (Ophthalmology, Epub date 2010/11/3). This transformation strategy was shown to remove the dependence of growth rates on the baseline size of GA.
GA area measurements, which were previously collected from 181 eyes of 181 AREDS study patients and followed longitudinally for up to four years, were analyzed using the square root transformation strategy. The correlation of lesion size change with baseline size was assessed on the original area scale and on the square root area scale with Pearson and Spearman correlation analyses. Baseline sizes were evaluated three ways: as an interval variable, with the published baseline disc area (DA) categories (<0.75DA, 0.75 - <4DA, ≥4DA), and by quintiles. The influences of the assigned treatments (zinc and antioxidants) were analyzed using the square root transformation strategy.
Four year growth rates were significantly correlated with baseline size on the original area scale (Pearson r=0.53, p<0.001; Spearman r=0.49, p<0.001), but not after square root transformation (Pearson r=0.10, p=0.30; Spearman r=0.17, p=0.08). Growth rates of areas per year were significantly different by baseline size category (p<0.001), but growth rates of square root areas were not different (p=0.34). Similar results were obtained with quintile baseline size categories. Neither zinc nor antioxidant treatment nor their interaction were associated with decreased lesion growth using either the original area or square root area measurements (all p>0.28)
The square root transformation strategy removed the dependence of GA growth rates on baseline GA area, confirming the recent report of Yehoshua et al. This will facilitate enrollment of patients with a wider range of baseline area into clinical trials for treatments designed to slow the enlargement rates of GA. Study designs should determine GA area exclusion criteria based on the treatment’s assumed mechanism of action, planned study duration, and clinically meaningful transformed changes. Reanalysis of the AREDS data did not alter the conclusions regarding a lack of treatment efficacy from the use of zinc and antioxidants.
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