Natural History of Geographic Atrophy
Ophthalmology Retina, September 2018
In geographic atrophy (GA) clinical trials, a change in a GA measure is usually selected as a primary outcome for evaluating treatment efficacy. However, estimates of GA progression rates in untreated eyes vary widely. Shen et al. evaluated the natural progression pattern of GA secondary to nonexudative age-related macular degeneration (AMD) in untreated eyes. They found that the radius of GA lesions increases linearly with time, with a high level of correlation across a wide range of studies.
For this review—believed to be the first meta-analysis on the topic—the authors included 25 studies with data from 2,942 eyes. They analyzed the data using the area linear model, the radius linear model (RLM), and the area exponential model. Of these 3 models, the RLM—in which GA radius grows linearly with time—proved to have the strongest predictive performance. A horizontal translation factor was added to account for the fact that participants entered into the individual studies at different time points in the history of their disease.
The results showed that GA radius continues to increase at a constant rate of 0.163 mm per year and that this growth rate is consistent across different age groups. The RLM also predicted the age of onset of GA as 67.4 ± 5.2 years.
Thus, the authors calculated, if a patient with GA presents at 67.4 years, the radius of the GA lesion would be 3.26 mm (20 × 0.163) 2 decades later. This is consistent with observations from clinical experience, as patients with GA often have lesions that occupy most of the area within the arcades at the latest stages of their disease.
The authors noted that this analysis only had data in GA sizes ranging from 2.46 to 20.3 mm2; thus, they said, they do not know if a similar fit is present for GA sizes outside of this range. Nonetheless, they suggested that the RLM be used in future clinical trials designed to evaluate the effect of a treatment on GA progression.
The original article can be found here.