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Original Investigation
August 1, 2019

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 12-Month Period: ProgStar Report No. 11

Author Affiliations
  • 1Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland
  • 2Moorfields Eye Hospital National Health Services Foundation Trust and UCL Institute of Ophthalmology, University College London, London, United Kingdom
  • 3Department of Ophthalmology, Johannes Kepler University Clinic Linz, Linz, Austria
  • 4Department of Ophthalmology, Medical University Graz, Graz, Austria
  • 5Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst
  • 6Doheny Eye Institute, David Geffen School of Medicine, University of California, Los Angeles
  • 7Moran Eye Center, University of Utah School of Medicine, Salt Lake City
  • 8Retina Foundation of the Southwest, Dallas, Texas
  • 9Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 10Sorbonne Universités, University Pierre et Marie Curie Université de Paris 06, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut de la Vision, Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
  • 11Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, University of Maryland School of Medicine, Baltimore, Maryland
  • 12Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
  • 13Center for Ophthalmology, Eberhard-Karls University Hospital, Tübingen, Germany
  • 14Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland
  • 15Department of Ophthalmology, University of Basel, Basel, Switzerland
JAMA Ophthalmol. 2019;137(10):1134-1145. doi:10.1001/jamaophthalmol.2019.2885
Key Points

Question  What is the growth rate of atrophic lesions in patients with Stargardt disease?

Findings  In this cohort study, the mean progression of definitely decreased autofluorescence lesions was 0.76 mm2 per year, and the mean progression of the area of total decreased fundus autofluorescence was 0.64 mm2 per year. Rates of progression depended on initial lesion size.

Meaning  The growth rate of atrophic lesions as determined by fundus autofluorescence may be a suitable outcome measure of treatment trials for patients with Stargardt disease.


Importance  Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease.

Objective  To estimate the progression rate of atrophic lesions in the prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study over a 12-month period.

Design, Setting, and Participants  This multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. Patients who were affected by Stargardt disease, aged 6 years and older at baseline, and harboring disease-causing variants of the ABCA4 gene were enrolled at 9 centers in the United States, United Kingdom, and continental Europe. Data analysis occurred from November 2016 to January 2017.

Exposures  Autofluorescence images obtained with a standard protocol were sent to a central reading center, and areas of definitely decreased autofluorescence, questionably decreased autofluorescence, and the total combined area of decreased autofluorescence were outlined and quantified. Progression rates were estimated from linear mixed models with time as the independent variable.

Main Outcomes and Measures  Yearly rate of progression, using the growth of atrophic lesions measured by autofluorescence imaging.

Results  A total of 259 study participants (488 eyes; 230 individuals [88.8%] were examined in both eyes) were enrolled (mean [SD] age at first visit, 33.3 [15.1] years; 118 [54.4%] female). Gradable images were available for evaluation for 480 eyes at baseline and 454 eyes after 12 months. At baseline, definitely decreased autofluorescence was present in 306 eyes, and the mean (SD) lesion size was 3.93 (4.37) mm2. The mean total area of decreased autofluorescence at baseline was 4.07 (4.04) mm2. The estimated progression of definitely decreased autofluorescence was 0.76 (95% CI, 0.54-0.97) mm2 per year (P < .001), and the total area of both questionably and definitely decreased autofluorescence was 0.64 (95% CI, 0.50-0.78) mm2 per year (P < .001). Both progression rates depended on initial lesion size.

Conclusions and Relevance  In Stargardt disease, autofluorescence imaging may serve as a monitoring tool and definitely decreased autofluorescence and total area as outcome measures for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.