Geographic Atrophy Growth Rate Strongly Associated With Lesion Perimeter

Researchers say the measurement unifies the effects of several morphological factors.

The growth rate of geographic atrophy (GA) area is strongly associated with mean GA perimeter, and GA perimeter-adjusted growth rate is not correlated with baseline GA area, lesion number and circularity index, researchers found in a retrospective analysis of participants in the Age-Related Eye Disease Study (AREDS). Instead, the investigators report, the GA perimeter unifies the effects of the 3 GA morphological factors. 

The research,  published in Ophthalmology Retina, sought to delineate GA lesions in eyes from the AREDS to test the hypothesis that GA perimeter unifies the apparent effects of baseline GA area, lesion number, and circularity index in patients with GA secondary to non-exudative age-related macular degeneration (AMD). The AREDS recruited 4757 participants aged 55 years to 80 years from 1992 to 1998 and annually took color fundus photographs (CFPs) of both eyes of the participants through December 2005. 

They included data from 318 eyes from 213 patients who participated in the AREDS via the database of Genotypes and Phenotypes (dbGaP) and manually delineated GA lesions on CFPs of all eyes that had GA without evidence of neovascular AMD based on the original AREDS gradings.

In 2 independent teams, which had a mean difference of -.01 mm2 and intraclass correlation coefficient of .997, the researchers assessed the reproducibility of GA area, perimeter and perimeter-adjusted growth rate and calculated 3 enlargement rates per eye: GA area growth rate, the growth rate of square root of GA area, and GA perimeter-adjusted growth rate.

They found that GA area growth rate was strongly associated with mean GA perimeter between the first and last visits (r2 =.66, P <.001), regardless of duration of follow-up between first and last visits (r2 ranges from 0.55 to 0.86). Geographic atrophy perimeter-adjusted growth rate remained consistent across different follow-up durations as well (r2 =.005, P =.11).

Through their multivariable linear mixed-effects model, they found that baseline geographic atrophy area, lesion number, and circularity index were independent prognostic factors for GA area growth rate (P <.001, P =.02, P <.001 respectively).

When they used the growth rate of square root of geographic atrophy area as the outcome measure, baseline number of lesions and circularity index were independently associated with growth rate of square root of GA area (P =.02 and P <.001 respectively) but geographic atrophy perimeter-adjusted growth rate was uncorrelated with all 3 (P =.47-.96).

With GA perimeter-adjusted growth rate as the outcome measure, geographic atrophy in the fellow eye at any visit was the only significant factor that remained associated with GA perimeter-adjusted growth rate (P =.002). That growth rate was 50% higher in eyes that had GA than those that did not have GA at any visit (0.102 mm/year ± 0.062 mm/year vs 0.068 mm/year ± 0.049 mm/year).

Limitations of the study included the researchers’ delineation of GA lesions based on CFP and most eyes in the analysis had a baseline GA area less than 30 mm2 and had less than 8 GAlesions.

Disclosure: One study author declared industry affiliations. Please see the original reference for a full list of authors’ disclosures.


Shen LL, Sun M, Ahluwalia A, et al. Geographic atrophy growth is strongly related to lesion perimeter: unifying effects of lesion area, number, and circularity on growth. Ophthalmology Retina. Published online December 9, 2020. doi:10.1016/j.oret.2020.12.002