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

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Retinal dystrophy; flavoprotein fluorescence; genetics; novel imaging.