Precursors and Development of Geographic Atrophy with Autofluorescence Imaging: Age-Related Eye Disease Study 2 Report No. 18

Abstract Purpose To describe the sequence of events leading to development of geographic atrophy (GA) in age-related macular degeneration (AMD) with fundus autofluorescence (FAF) imaging. Design Post hoc analysis of FAF images from the Age-Related Eye Disease Study 2. Participant FAF images of 120 eyes (109 patients) with incident GA and at least 2 years of preceding FAF images. Methods Images of incident GA were stacked and aligned over FAF images of preceding annual visits. The regions of retina that developed into incident GA were assessed on prior years FAF images. These regions, defined as precursor lesions were classified into Minimal ChangeAF, Predominant HypoAF (decreased AF), Predominant HyperAF (increased AF), and MixedAF. The natural progression in precursor lesions leading to GA formation and their associations with incident GA size and GA enlargement rate was evaluated. Results Incident GA had a mean area of 1.00 mm 2 (range 0.15 - 8.22 mm 2 ) and an enlargement rate of 0.97 mm 2 /year (SD 1.66). Predominant HypoAF was the most common precursor lesion, increasing from 42% to 81% over 3 years prior to onset of GA. Almost 30% of eyes had Minimal ChangeAF 3 years prior to GA. Among the other precursors, 70% progressed to Predominant HypoAF before developing GA. The type of precursor lesions was not associated with incident GA area. GA evolving from Minimal ChangeAF precursor lesions was associated with faster GA enlargement rates compared to other precursor lesion classes. Conclusion Using image registration we identified changes in AF mages prior to onset of GA. Decreased autofluorescence was the most common change although minimal changes were also seen in a third of the images. Incident GA that arises from predominantly normal AF is associated with faster enlargement rates compared to GA arising from abnormal AF. Faster GA enlargement rates were also associated with incident GA size, area of surround abnormal autofluorescence, and presence of reticular pseudodrusen.