Quantitative Flavoprotein Fluorescence Parameters in Retinal and Optic Nerve Diseases: A Scoping Review

Background: Retinal and optic nerve disorders remain major causes of visual morbidity worldwide. Ocular fundus flavoprotein fluorescence (FPF) imaging has emerged as a potential noninvasive biomarker of mitochondrial dysfunction for earlier detection and evaluation of disease severity. Methods: We conducted a Systematic Scoping Review of the diagnostic and correlational utility of quantitative FPF parameters in retinal and optic nerve diseases compared with healthy controls. Following PRISMA-ScR guidelines, we searched MEDLINE, Web of Science, Scopus, and CENTRAL for peer-reviewed human studies available online before 31 December 2025. Results: Seventeen studies were included, encompassing 1914 eyes and 1339 participants, and were predominantly cross-sectional. In healthy eyes, mean macular and optic nerve head FPF intensity were reported as 24.1 ± 12.2 gsu and 30.6 ± 14.6 gsu, respectively. Higher signals were reported in several disorders, including diabetes mellitus (76.0 [67.0-92.0] gsu), neovascular age-related macular degeneration (67.47 ± 17.77 gsu), and retinitis pigmentosa (50.5 ± 12.2 gsu). However, lower, unchanged, or stage-dependent signals were also observed within the same disease categories. Interpretation across studies was limited by substantial heterogeneity in patient selection, disease definitions, imaging protocols, control groups, and FPF outcome metrics. The precise cellular and sublayer origin of the detected signal also remains challenging to determine. Conclusions: Ocular fundus FPF imaging provides promising metabolic insight into retinal and optic nerve diseases. However, current evidence remains heterogeneous and largely cross-sectional, limiting clinical interpretability and generalizability. Longitudinal studies, technical standardization, and multimodal integration are needed to define reproducible disease-specific FPF profiles and improve translational applicability.