Progression of stargardt disease as determined by fundus autofluorescence in the retrospective progression of stargardt disease study (ProgStar report no. 9)

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.