Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Flavoprotein Fluorescence in Stargardt's Disease: a prospective multimodal imaging study
Author Affiliations & Notes
  • David Adrian Merle
    Ophthalmology, University Clinic Tübingen, Tübingen, Baden-Württemberg, Germany
    Ophthalmology, Medizinische Universitat Graz, Graz, Steiermark, Austria
  • Veronica Cuevas-Villanueva
    Ophthalmology, University Clinic Tübingen, Tübingen, Baden-Württemberg, Germany
  • Ronja Jung
    Ophthalmology, University Clinic Tübingen, Tübingen, Baden-Württemberg, Germany
  • Melanie Kempf
    Ophthalmology, University Clinic Tübingen, Tübingen, Baden-Württemberg, Germany
  • Krunoslav Stingl
    Ophthalmology, University Clinic Tübingen, Tübingen, Baden-Württemberg, Germany
  • Katarina Stingl
    Ophthalmology, University Clinic Tübingen, Tübingen, Baden-Württemberg, Germany
  • Footnotes
    Commercial Relationships   David Merle None; Veronica Cuevas-Villanueva None; Ronja Jung None; Melanie Kempf None; Krunoslav Stingl None; Katarina Stingl Novartis, ProQR, ViGeneron, Santen, Janssen, Code C (Consultant/Contractor)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 5877. doi:
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      David Adrian Merle, Veronica Cuevas-Villanueva, Ronja Jung, Melanie Kempf, Krunoslav Stingl, Katarina Stingl; Flavoprotein Fluorescence in Stargardt's Disease: a prospective multimodal imaging study. Invest. Ophthalmol. Vis. Sci. 2024;65(7):5877.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Flavoprotein Fluorescence (FPF) imaging offers deeper insights into the metabolic health of the retina by detecting the natural fluorescence of flavoproteins, crucial components in mitochondrial energy production. Given that only oxidized flavoproteins are fluorescent, an increase in FPF intensity indicates a redox imbalance caused by heightened oxidative stress or disruptions in the mitochondrial electron transport chain.
Despite being a promising new technique, only a few studies on FPF in common retinal diseases have been published and correlation to other imaging modalities is lacking. In Stargardt’s disease type 1 (STGD1), impaired ABCA4 function leads to profound metabolic disturbance in the outer retina and toxic accumulations of vitamin A derivatives. Therefore, STGD1 is a promising target for FPF-based studies.

Methods : 34 subjects with genetically confirmed ABCA4-associated STGD1 were recruited at the University Eye Hospital Tübingen from June till Nov. 2024. Subjects underwent wide-field fundus photography, wide-field fundus autofluorescence (FAF) and optical coherence tomography (OCT). FPF images were taken using OcuMet Beacon (OcuSciences, USA). FPF images were manually correlated with OCT and FAF to identify structural alterations corresponding to increased or decreased FPF signals. Additionally, OCT scans were manually segmented and correlated to FPF intensity maps to provide 2-dimensional correlation maps using a custom MATLAB script.

Results : FPF signal correlated with distinct OCT features. Manual correlation enabled definition of a set of characteristic OCT features that correspond to altered FPF signals. In general, FPF intensity correlated with the extent of retinal damage in OCT scans: FPF values were normal in unaffected retinal regions, elevated in transitional zones and diminished in regions of outer retinal atrophy. FAF alterations did not consistently correlate with FPF signals and in some instances FPF alterations appeared in regions devoid of FAF lesions.

Conclusions : The ability to provide metabolic readouts in vivo makes FPF imaging a promising technique to detect early signs of metabolic stress in STGD1 and potentially in many other retinal diseases. FPF imaging may significantly contribute to our understanding of disease pathophysiology and may provide novel biomarkers for clinical trials, especially in the context of Stargardt’s disease.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

FPF correlation with FAF and OCT

FPF correlation with FAF and OCT

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