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. 2007 Feb;114(2):271-7.
doi: 10.1016/j.ophtha.2006.09.016.

The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials

Janet S Sunness  1 , Eyal Margalit, Divya Srikumaran, Carol A Applegate, Yan Tian, Daniel Perry, Barbara S Hawkins, Neil M Bressler
Affiliations

The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials

Janet S Sunness et al. Ophthalmology. 2007 Feb.

Abstract

Purpose: To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA.

Design: Prospective natural history study of GA resulting from age-related macular degeneration.

Participants: Two hundred twelve eyes of 131 patients were included in the analysis.

Methods: Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined.

Main outcome measure: Rate of enlargement of the atrophy.

Results: The median overall enlargement rate was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (alpha, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye.

Conclusions: Treatment trials for GA with an outcome variable of change in enlargement rate are feasible.

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Conflict of interest statement

No conflicting relationship exists for any of the authors.

Figures

Figure 1
Figure 1
Fundus photographs of 3 eyes showing the variation between patients in enlargement rate and the consistency of enlargement rate over time. The areas of atrophy are outlined. Top, Low enlargement rate. Left, Baseline atrophic area was 11.2 mm2 (4.4 Macular Photocoagulation Study [MPS] disc areas). Center, Appearance at 2.0 years. The enlargement rate was 0.3 mm2/year for the first 2 years. Right, Appearance at 4.0 years. The enlargement rate was 0.5 mm2/year for the second 2 years. Middle, Enlargement rate near the mean. Left, Baseline atrophic area was 10.9 mm2 (4.3 MPS disc areas). Center, Appearance at 2.3 years. The enlargement rate was 2.8 mm2/year for the first 2 years. Right, Appearance at 4.0 years. The enlargement rate was 3.3 mm2/year for the second 2 years. Bottom, High enlargement rate. Left, Baseline atrophic area was 8.9 mm2 (3.5 MPS disc areas). Center, Appearance at 2.2 years. The enlargement rate was 6.1 mm2/year for the first 2 years. Right, Appearance at 4.3 years. The enlargement rate was 4.6 mm2/year for the second 2 years.
Figure 2
Figure 2
Scatterplot showing the 2-year enlargement rate as a function of baseline area of atrophy.
Figure 3
Figure 3
Scatterplot showing the subsequent 2-year enlargement rate versus the first 2-year enlargement rate. There is strong correlation between these measures (correlation coefficient, 0.58).
Figure 4
Figure 4
Scatterplot showing the concordance in enlargement rate between eyes in patients with bilateral geographic atrophy (GA). The correlation coefficient was 0.76. The strong concordance between eyes will allow for a small sample size when conducting future uniocular studies that treat 1 eye and use the fellow eye as a control.
See this image and copyright information in PMC

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