Flavoprotein Fluorescence Imaging in Stargardt Disease: Linking Metabolic Stress to Structural Damage

Stargardt disease (SD) is an inherited retinal disorder that leads to progressive vision loss. Currently, no approved treatments exist. Identifying early metabolic changes in the retina could be critical for the development of new therapies. Flavoprotein fluorescence (FPF) imaging has the potential to serve as a non-invasive biomarker for detecting these early changes before structural damage is evident. Therefore, this study evaluated FPF patterns in patients with SD and correlated these findings with structural imaging modalities, specifically fundus autofluorescence (FAF) and optical coherence tomography (OCT). This cross-sectional study enrolled 36 subjects with genetically confirmed ABCA4-associated SD between June 1, 2023, and January 31, 2024, at the University Eye Clinic Tübingen, Germany. FPF patterns were qualitatively and quantitatively analyzed and correlated with FAF and OCT findings to identify distinct lesion types. Several distinct lesion types were identified based on FPF signal patterns and their correlation with FAF and OCT findings. Increased FPF signals were primarily associated with outer retinal damage. In some cases, increased FPF was observed in the absence of significant structural changes, indicating early metabolic stress. This study demonstrates that FPF imaging is a promising tool for detecting early metabolic changes in Stargardt disease, potentially serving as a non-invasive biomarker for monitoring disease progression and treatment response. However, current FPF imaging technology is insufficient to discern true FPF signals from lipofuscin-derived fluorescence, making location-specific and FAF comparative analyses imperative and highlighting the need for longitudinal studies.