Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 24-Month Period (ProgStar Report No. 17)

Rupert W Strauss; Alexander Ho; Anamika Jha; Kaoru Fujinami; Michel Michaelides; Artur V Cideciyan; Isabelle Audo; David G Birch; Srinivas Sadda; Michael Ip; Sheila West; Etienne M Schönbach; Xiangrong Kong; Hendrik P N Scholl; Progstar Study Group

doi:10.1016/j.ajo.2023.02.003

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 24-Month Period (ProgStar Report No. 17)

Am J Ophthalmol. 2023 Jun:250:157-170. doi: 10.1016/j.ajo.2023.02.003. Epub 2023 Feb 9.

Authors

Affiliations

¹ From the Department of Ophthalmology, Medical University Graz (R.W.S.), Graz, Austria; Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, University College London (R.W.S., K.F., M.M.), London, United Kingdom; Department of Ophthalmology, Kepler University Clinic (R.W.S.), Linz, Austria; Institute of Clinical and Molecular Ophthalmology Basel (IOB) (R.W.S., H.P.N.S.), Basel, Switzerland.
² Doheny Eye Institute, David Geffen School of Medicine at University of California Los Angeles (A.H., A.J., S.S., M.I.), California, USA.
³ Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, University College London (R.W.S., K.F., M.M.), London, United Kingdom; Laboratory of Visual Physiology, Division for Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center (K.F.), Tokyo, Japan.
⁴ Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, University College London (R.W.S., K.F., M.M.), London, United Kingdom.
⁵ Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania (A.V.C.), Philadelphia, Pennsylvania, USA.
⁶ Sorbonne Universités, University Pierre et Marie Curie (UPMC) Université de Paris 06, Institut national de la santé et de la recherche médicale (INSERM), Centre national de la recherche scientifique (CNRS), Institut de la Vision, Centre Hospitalier National d'Ophtalmologie (CHNO) des Quinze-Vingts (I.A.), Paris, France.
⁷ Retina Foundation of the Southwest, Dallas (D.G.B.), Texas, USA.
⁸ Wilmer Eye Institute, Johns Hopkins University (S.W., X.K.), Baltimore, USA.
⁹ Shiley Eye Institute and Jacobs Retina Center, University of California, San Diego (E.M.S.), La Jolla, California, USA.
¹⁰ Institute of Clinical and Molecular Ophthalmology Basel (IOB) (R.W.S., H.P.N.S.), Basel, Switzerland; Department of Ophthalmology, University of Basel (H.P.N.S.), Basel, Switzerland. Electronic address: Hendrik.Scholl@iob.ch.

PMID: 36764427
DOI: 10.1016/j.ajo.2023.02.003

Abstract

Purpose: To estimate the progression rate of atrophic lesions in Stargardt disease derived from fundus autofluorescence (FAF).

Design: International, multicenter, prospective cohort study.

Methods: A total of 259 participants aged ≥6 years with disease-causing variants in the ABCA4 gene were enrolled from 9 centers and followed over a 24-month period. FAF images were obtained every 6 months, and areas of definitely decreased autofluorescence (DDAF) and decreased autofluorescence (DAF) were quantified. Progression rates were estimated from linear mixed models with time as the independent variable.

Results: A total of 488 study eyes of 259 participants (88.8% with both eyes) were enrolled and images from 432 eyes were followed for 24 months. The overall estimated progression of DDAF was 0.74 mm²/y (95% CI 0.64-0.85, P < .0001) and that of DAF was 0.64 mm²/y (95% CI 0.57-0.71) over a 24-month period in univariate analysis. Growth rates were strongly dependent on baseline lesion area. After square root transformation, the DDAF growth rate was not dependent on baseline lesion radius (P = .11), whereas the DAF growth rate was dependent (P < .0001). Genotype was not found to significantly impact the growth rate of DDAF or DAF lesions.

Conclusions: FAF may serve as a convenient monitoring tool and suitable end point for interventional clinical trials that aim to slow disease progression. DDAF and DAF lesion sizes at baseline are strong predicting factors for lesion area growth and can be partially accounted for by square root transformation.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

ATP-Binding Cassette Transporters / genetics
Disease Progression
Fluorescein Angiography
Fundus Oculi
Humans
Macular Degeneration* / diagnosis
Macular Degeneration* / genetics
Prospective Studies
Stargardt Disease
Visual Acuity

Substances

ABCA4 protein, human
ATP-Binding Cassette Transporters

Grants and funding

R21 EY032955/EY/NEI NIH HHS/United States