Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence

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Purpose: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. Methods: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. Results: Three hundred fifty-six eyes (178 AMD eyes, 178 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity ( P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity ( P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity ( P = 0.018 and 0.024, respectively). Conclusions: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:24–31.]

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