Functional imaging of mitochondria in genetically confirmed retinal dystrophies using flavoprotein fluorescence

Whether by indirect oxidative stress or direct genetic defect, various genetic retinal dystrophies involve mitochondrial stress. Mitochondrial flavoprotein fluorescence (FPF), reported as either average signal intensity or variability (heterogeneity), may serve as a direct, quantifiable marker of oxidative stress. This observational study enrolled patients with genetically confirmed retinal dystrophies between January and December 2021. Patients with concomitant maculopathy and ocular hypertension were excluded. Patients were FPF imaged with OcuMet Beacon® third generation device during routine outpatient visit. The final analysis cohort included 242 images from 157 patients. Mean FPF intensity was significantly increased between age matched controls and patients with confirmed rod-cone dystrophy, Stargardt disease, Bardet-Biedl syndrome (BBS), and Mitochondrial ATP synthase mutation (P ≤ 0.007). Mean FPF heterogeneity was significantly increased between age matched controls and patients with confirmed rod-cone dystrophy, Stargardt disease, and BBS (P ≤ 0.011). FPF lesions were noted to correlate with Fundus Autofluorescence (FAF) lesions in diseases examined. FPF intensity and heterogeneity significantly increased in patients with retinal dystrophies. The correlation of FPF lesions with FAF lesions implies FPF may be a clinically useful biomarker in patients with IRDs. This study found increases in flavoprotein fluorescence signal in patients with genetically confirmed inherited retinal dystrophies compared to age matched controls. Flavoprotein fluorescence signal correlated with fundus autofluorescence findings, suggesting clinical utility of novel signal. What is already known on the topic: Flavoprotein Fluorescence imaging has been examined to be increased in one patient with retinitis pigmentosa. However, characterization of this signal over large patient cohorts with inherited retinal dystrophies is unknown. What this study adds: This study shows increases in Flavoprotein Fluorescence across a broad range of patients with Inherited Retinal Dystrophies, and shows correlation of signal to clinically relevant imaging modalities. How this study might affect research, practice, or policy: This study highlights the potential of Flavoprotein Fluorescence imaging to be used in patients with Inherited Retinal Dystrophies. Further longitudinal studies will elucidate the value of this signal in this patient population.