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Original Investigation
November 2017

Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9)

Author Affiliations
  • 1Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland
  • 2Moorfields Eye Hospital National Health Service Foundation Trust, London, England
  • 3University College London Institute of Ophthalmology, University College London, London, England
  • 4Department of Ophthalmology, Medical University Graz and Johannes Kepler University Linz, Linz, Austria
  • 5Department of Ophthalmology, University of Basel, Basel, Switzerland
  • 6Doheny Eye Institute, David Geffen School of Medicine at University of California–Los Angeles
  • 7Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 8Sorbonne Universités, University Pierre et Marie Curie Université de Paris 06, Paris, France
  • 9Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
  • 10Centre National de la Recherche Scientifique, Institut de la Vision, Paris, France
  • 11Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
  • 12Retina Foundation of the Southwest, Dallas, Texas
JAMA Ophthalmol. 2017;135(11):1232-1241. doi:10.1001/jamaophthalmol.2017.4152
Key Points

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

Findings  In this multicenter cohort study, mean progression of definitely decreased autofluorescence lesions was 0.51 mm2/y, and of total decreased fundus autofluorescence was 0.35 mm2/y. Rates of progression depended on initial lesion size.

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


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

Objective  To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study.

Design, Setting, and Participants  A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye.

Exposures  Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. 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 fundus autofluorescence.

Results  A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of progression depended on the initial size of the lesion.

Conclusions and Relevance  In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.