Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5

IMPORTANCE: Outcome measures that are sensitive to disease progression are needed as clinical end points for future treatment trials in Stargardt disease. OBJECTIVE: To examine the incidence of atrophic lesions of the retinal pigment epithelium in patients with Stargardt disease as determined by fundus autofluorescence imaging. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective multicenter cohort study, 217 patients 6 years and older at baseline at tertiary referral centers in Europe, the United States, and the United Kingdom who were harboring disease-causing variants in the adenosine triphosphate (ATP)-binding cassette subfamily A member 4 (ABCA4) gene and who met the following criteria were enrolled: (1) at least 1 well-demarcated area of atrophy with a minimum diameter of 300 μm, with the total area of all atrophic lesions being less than or equal to 12 mm² in at least 1 eye at the most recent visit, and (2) fundus autofluorescence images for at least 2 visits with a minimum of 6 months between at least 2 visits. Data were collected between August 22, 2013, and December 12, 2014. Data analysis was performed from March 15, 2015, through January 31, 2017. EXPOSURES: Images were evaluated by staff at a central reading center. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) were outlined and quantified. Lesion-free survival rates were estimated using Kaplan-Meier survival curves. MAIN OUTCOMES AND MEASURES: Incidence of atrophic lesions as determined by fundus autofluorescence. RESULTS: The 217 patients (mean [SD] age, 21.8 [13.3] years; 127 female [57.5%]; 148 white [68.2%]) contributed 390 eyes for which the mean (SD) follow-up time was 3.9 (1.6) years (range, 0.7-12.1 years). Among eyes without DDAF at first visit, the median time to develop a DDAF lesion was 4.9 years (95%CI, 4.3-5.6 years). Among eyes without QDAF, the median time to develop a QDAF lesion was 6.3 years (95%CI, 5.6-9.7 years). Eyes with a lesion of DDAF at the first visit were less likely to develop a QDAF lesion compared with eyes without a lesion of DDAF (hazard ratio, 0.19; 95%CI, 0.05-0.70; P = .01). CONCLUSIONS AND RELEVANCE: An estimated 50% of the eyes without DDAF at first visit will develop the lesion in less than 5 years, suggesting that incidence of DDAF could serve as an outcome measure for treatment trials.