Variability in fundus autofluorescence (FAF) intensity is locally and globally associated with rod-mediated dark adaptation (RMDA) delay in early age-related macular degeneration (AMD)

Abstract

Purpose : The retinal pigment epithelium (RPE) is the major signal source for blue FAF. Histology of human RPE in AMD reveals variable cell morphologies, layer thickening, and re-distribution and loss of autofluorescent granules. RMDA depends on RPE health, and RMDA delay is a risk factor for incident AMD. We examined the association between variability in FAF intensity and RMDA in eyes with and without AMD.

Methods : FAF images of persons ≥60 years old enrolled in the ALSTAR study underwent semi-automated masking of the vasculature and optic disk to reduce variability associated with non-AF structures. Coefficient of variation (CV) (standard deviation of intensity / mean intensity) was assessed within the ETDRS grid and its central (C1) and superior inner (S3) subfields. RMDA was assessed after an 83% photobleach with targets centered at 5° on superior vertical retinal meridian (in S3). Time (minutes) required for sensitivity recovery to 5.0 X 10^-3 scotopic cd/m² was defined as the rod-intercept (RI). Measurements were repeated 3 years later. Spearman correlation coefficients (SCC) adjusting for age were used to assess the cross-sectional association between CV of FAF and RI and the change in measurements over time.

Results : There were 544 eyes in the baseline cross-sectional analysis and 322 eyes in the follow-up analysis. At baseline age-adjusted SCC between FAF CV and RI in eyes in normal macular health in C1, S3, and the full ETDRS grid was 0.04 (p=0.39), 0.08 (p=0.10), and 0.08 (p=0.09) respectively. In eyes with early AMD, SCC was 0.07 (p=0.43), 0.19 (p=0.03), and 0.19 (p=0.03) in the same regions. The age-adjusted SCC between change in FAF CV and change in RI from baseline to 3-year follow-up in eyes in normal macular health in C1, S3 and the full ETDRS grid was 0.001 (p=0.98), -0.02 (p=0.71), and 0.03 (p=0.59), respectively. In eyes with AMD, the correlation was 0.29 (p=0.049), 0.32 (p=0.030), and 0.47 (p=0.0009) in the same regions.

Conclusions : Increased FAF variability in early AMD is associated with slowing in RMDA, a previously identified risk factor for early AMD. In eyes with early AMD, increasing FAF variability over three years is associated with further slowing of RMDA. Semi-automated analysis of FAF may offer a novel approach for evaluating how RPE health impacts RMDA in aging and AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.