Impact of the Convex Hull of Abnormal Fundus Autofluorescence on the Progression of Geographic Atrophy in Patients With AMD

Abstract

Abstract: : Purpose:We have previously shown that increased fundus autofluoresecence (FAF) in the junctional zone of geographic atrophy (GA) precedes development of new and enlargement of existing areas of GA in AMD (IOVS 1999) and causes functional impairment prior to the occurrence of cell death (IOVS 2004). Here we tested the hypothesis that the extent of the area with increased FAF outside atrophic patches is correlated with the degree of spread of GA over time in eyes with advanced atrophic AMD. Methods:41 eyes of 34 patients (age 73.37 ± 7.44 years) with GA were included from the longitudinal natural history arm of the multicenter FAM (Fundus Autofluorescence in Age–Related Macular Degeneration)–Study. In standardized digital FAF images (HRA, exc 488 nm, em >500 nm) obtained at baseline and 6–months intervals, total size and spread of GA was measured (mean follow–up 2.36 ± 1.75 years). The convex hull of increased FAF as the minimum polygon encompassing the entire area of abnormal FAF surrounding the central atrophic patches was quantified at baseline for each eye. Statistical analysis was performed using the Spearman’s rank correlation coefficient (rho). Results:At baseline, total size of atrophy ranged from 1.04 mm² to 20.09 mm² with a mean of 7.41 ± 4.53 mm². Mean size of the convex hull was 22.67 ± 10.12 mm². Average rate of GA progression was 2.05 ± 1.38 mm² per year. The difference between the convex hull and the total GA size at baseline showed a positive correlation with the degree of spread of GA over time (rho = 0.46; p=0.0035). Conclusions:Eyes with larger extent of areas of increased FAF outside atrophy at baseline show greater progression rates of GA compared to eyes with smaller extension of abnormal FAF. FAF findings not detectable by fundus photography or fluorescence angiography may therefore serve as prognostic determinants in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings underscore the potential pathophysiological relevance of LF as a common pathogenetic pathway in hereditary and complex retinal diseases.

Keywords: age-related macular degeneration • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • retinal pigment epithelium