for the ProgStar Study Group 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 PARTICIPANTSA 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 MEASURESYearly 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) mm 2 . The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm 2 . Mean progression of DDAF was 0.51 mm 2 /y (95% CI, 0.42-0.61 mm 2 /y), and of total decreased fundus autofluorescence was 0.35 mm 2 /y (95% CI, 0.28-0.43 mm 2 /y). Rates of progression depended on the initial size of the lesion. CONCLUSIONS AND RELEVANCEIn 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.

IMPORTANCESensitive 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 PARTICIPANTSThis 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 MEASURESYearly 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) mm 2 . The mean total area of decreased autofluorescence at baseline was 4.07 (4.04) mm 2 . The estimated progression of definitely decreased autofluorescence was 0.76 (95% CI, 0.54-0.97) mm 2 per year (P < .001), and the total area of both questionably and definitely decreased autofluorescence was 0.64 (95% CI, 0.50-0.78) mm 2 per year (P < .001). Both progression rates depended on initial lesion size. CONCLUSIONS AND RELEVANCEIn 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.

Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets.