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

Rupert W Strauss; Xiangrong Kong; Alexander Ho; Anamika Jha; Sheila West; Michael Ip; Paul S Bernstein; David G Birch; Artur V Cideciyan; Michel Michaelides; José-Alain Sahel; Janet S Sunness; Elias I Traboulsi; Eberhart Zrenner; Sean Pitetta; Dennis Jenkins; Amir Hossein Hariri; SriniVas Sadda; Hendrik P N Scholl; ProgStar Study Group

doi:10.1001/jamaophthalmol.2019.2885

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

JAMA Ophthalmol. 2019 Oct 1;137(10):1134-1145. doi: 10.1001/jamaophthalmol.2019.2885.

Authors

Rupert W Strauss^{1

2

3

4}, Xiangrong Kong^{1

5}, Alexander Ho⁶, Anamika Jha⁶, Sheila West¹, Michael Ip⁶, Paul S Bernstein⁷, David G Birch⁸, Artur V Cideciyan⁹, Michel Michaelides², José-Alain Sahel¹⁰, Janet S Sunness¹¹, Elias I Traboulsi¹², Eberhart Zrenner¹³, Sean Pitetta⁶, Dennis Jenkins⁶, Amir Hossein Hariri⁶, SriniVas Sadda⁶, Hendrik P N Scholl^{1

14

15}; ProgStar Study Group

Affiliations

¹ Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.
² Moorfields Eye Hospital National Health Services Foundation Trust and UCL Institute of Ophthalmology, University College London, London, United Kingdom.
³ Department of Ophthalmology, Johannes Kepler University Clinic Linz, Linz, Austria.
⁴ Department of Ophthalmology, Medical University Graz, Graz, Austria.
⁵ Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst.
⁶ Doheny Eye Institute, David Geffen School of Medicine, University of California, Los Angeles.
⁷ Moran Eye Center, University of Utah School of Medicine, Salt Lake City.
⁸ Retina Foundation of the Southwest, Dallas, Texas.
⁹ Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
¹⁰ Sorbonne 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.
¹¹ Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, University of Maryland School of Medicine, Baltimore, Maryland.
¹² Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
¹³ Center for Ophthalmology, Eberhard-Karls University Hospital, Tübingen, Germany.
¹⁴ Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
¹⁵ Department of Ophthalmology, University of Basel, Basel, Switzerland.

Abstract

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.