Square Root of Baseline Lesion Number is a Correction Factor for the Geographic Atrophy Growth Rate

Abstract

Purpose : The effective radius (square root of (total GA area/π)) of geographic atrophy (GA) has been proposed as a primary endpoint in treatment trials for GA secondary to age-related macular degeneration. Studies have shown that although the effective radius growth rate (ERGR) was independent of baseline GA size, the ERGR was much higher in multifocal (≥2 lesions) vs. unifocal (1 lesion) GA. We tested the hypothesis that using a correction of the square root of baseline lesion number could eliminate the apparent effect of lesion number on the ERGR.

Methods : We manually segmented GA in color photographs from 1539 visits of 346 eyes (follow-up = 5.1±2.9 years) in the AREDS database. We calculated the adjusted GA effective radius as square root of (total GA area/[π × baseline lesion number]). In an eye with multifocal GA, the adjusted effective radius represented the average radius of all lesions. To correct for different patients’ entry times into the study, we added a horizontal translation factor to shift each dataset 1 month at a time until r² was maximized for the cumulative trendline.

Results : After horizontally shifting datasets in Fig.1A, we realigned the datasets onto a straight line (r² =0.96; Fig.1B), suggesting a steady linear enlargement of the adjusted effective radius of GA over ~30 years. The ERGR of multifocal GA (0.186 mm/year) was 65% higher than that of unifocal GA (0.113 mm/year) (P<0.001; Fig. 2A); in contrast, after the introduction of square root of baseline lesion number, the adjusted ERGR of multifocal GA (0.106 mm/year) was similar to the growth rate of unifocal GA (P=0.40; Fig. 2B). This adjustment also eliminated the dependence of ERGR on baseline lesion number (P=0.72; compare Fig. 2C and D).

Conclusions : Using the square root of baseline lesion number eliminates the impact of number of lesions on GA growth rate. The data implies that unifocal and multifocal GA may share the same expansion mechanism. The use of the adjusted ERGR may reduce variations in GA growth rates among patients and improve the sensitivity detecting an effect in a treatment trial.

This is a 2020 ARVO Annual Meeting abstract.

 

Fig. 1 After the introduction of horizontal translation factors to raw datasets in (A), the datasets in (B) were realigned onto a straight line over ~30 years.

 

Fig. 2 (A) and (B) compare growth rates between unifocal and multifocal GA. (C) and (D) compare growth rates among eyes with different number of GA lesions.