n Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of age-related macular degeneration (AMD). As increased flavoprotein fluorescence (FPF) is indicative of mitochondrial dysfunction, we assessed mitochondrial dysfunction in AMD eyes using FPF. AMD eyes with geographic atrophy (GA) showed significant qualitative and quantitative FPF heterogeneity in the retina (Figures 4-6), whereas age-matched control eyes showed no significant heterogeneity (Figures 1-3). FPF heterogeneity indicates that an increased variability in mitochondrial dysfunction seems to be present in eyes with advanced disease. Additionally, mean FPF average intensities of AMD eyes with (p=0.044) and without (p=0.00060) GA were significantly greater than that of control eyes.

This study indicates that FPF can be used to qualitatively and quantitatively detect AMD-induced mitochondrial dysfunction. Future studies will be conducted to further assess the utility of FPF in detecting and evaluating AMD-induced metabolic alterations of the macula, including longitudinal studies on larger patient sets to determine the ability of FPF to monitor AMD disease progression and mitigation with treatment.

We have also recently contracted with a pharmaceutical company to use our RMA technology that measures FPF to assess the impact of various drug candidates on improving the metabolic status of AMD patients.  

Figs 1-3. FPF of normal eyes. Color fundus photographs with the FPF analysis area highlighted in black (1A, 2A, 3A), corresponding FPF images (1B, 2B, 3B), and FPF images after anisotropic diffusion filtration (1C, 2C, 3C) of 73 (1A-C), 79 (2A-C), and 34 (4A-C) year old eyes.

Figs 4-6. FPF of advanced dry (nonexudative) AMD eyes with GA. Color fundus photographs with the selected FPF analysis area highlighted in black (4A, 5A, 6A), corresponding FPF images (4B, 5B, 6B), and FPF images after anisotropic diffusion filtration (4C, 5C, C) of 71 (4A-C), 79 (5A-C), and 83 (6A-C) year old eyes with advanced dry AMD and GA.