New grading criteria allow for earlier detection of geographic atrophy in clinical trials

Abstract

Purpose: To evaluate new grading criteria for geographic atrophy (GA), as detected by annual stereoscopic color fundus photographs and fluorescein angiograms, and to assess whether application of the revised criteria provides earlier identification of GA than previous criteria involving only color fundus photography.

Methods: Annual fundus image sets from 114 CAPT patients who developed GA in the untreated eye during 5 to 6 years of follow-up were reassessed for the presence of GA, using revised grading criteria, in which GA was defined by (1) the presence of hyperfluorescence on fluorescein angiography; and (2) at least one other characteristic indicative of involution of the retinal pigment epithelium (i.e., sharp edges, excavation of the retina, or visible choroidal vessels on either color images or fluorescein angiograms). Reliability and time of initial detection of GA using the revised criteria were assessed.

Results: The revised criteria are reliable (97.8% intragrader, 93.3% intergrader agreement) and accurate (false-positive rate, 0.8%) for detecting individual early GA lesions. Using this revised method, individual GA lesions were identified 1-year earlier on average than was possible with criteria used in previous CFP studies. The use of two imaging modalities was more sensitive in detecting GA and its features than either imaging modality alone (P ≤ 0.0001).

Conclusions: Early GA areas can be reliably identified when defining criteria are based on both color photographs and fluorescein angiograms. These methods can be used to investigate the natural history of GA earlier in the course of disease than previously possible and to facilitate the design of future clinical trials of treatments for GA. (ClinicalTrials.gov number, NCT00000167).

Figures

Figure 1.

Comparison of the cumulative probability of GA detection by year since enrollment in the original CAPT study using the revised criteria versus the standard criteria (CAPT definition).

Figure 2.

Comparison of CFP and FA for detecting and measuring GA. (A) Color photograph of an eye with GA, in which the fundus is lightly colored, allowing the choroidal vessels to be seen under areas of GA as well as intact RPE. In this case, it is difficult to delineate GA from color photography alone. (B) The areas of atrophy and depigmentation are more clearly distinguished on the corresponding fluorescein angiogram. (C) Color photograph from an eye with several areas of GA with multiple drusen and areas of depigmentation and hyperpigmentation obscuring the borders of atrophy. It is difficult to determine the exact margins of GA from color photography alone. (D) The borders of GA and the spared areas of the fovea in between the lesions are more apparent on the corresponding fluorescein angiogram.