• Atrophic Lesions and Progression in Patients With Stargardt Disease

    Written By: Lynda Seminara and selected by Neil M. Bressler, MD, and Deputy Editors

    Journal Highlights

    JAMA Ophthalmology, July 2017

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    Strauss et al. set out to determine the incidence of atrophic lesions of the reti­nal pigment epithelium among patients with Stargardt disease. They found that approximately 50% of eyes without areas of definitely decreased autofluo­rescence at the initial visit developed an atrophic lesion within 5 years.

    For this retrospective multicenter study—known as the Natural History of the Progression of Atrophy Second­ary to Stargardt Disease (ProgStar) Study—the researchers assessed 217 patients (390 eyes). All of the patients had disease-causing variants in the adenosine triphosphate (ATP)–bind­ing cassette subfamily A member 4 (ABCA4) gene. To be enrolled in the study, they had to meet the following 2 criteria: 1) They had to have at least 1 well-demarcated area of atrophy ≥ 300 μm in diameter, with the total area of atrophic lesions ≤ 12 mm2 in at least 1 eye at the most recent visit, and 2) they had to have fundus autofluorescence images for at least 2 visits, with a mini­mum of 6 months between at least 2 of these visits.

    All patients were ≥ 6 years old at baseline (mean, 22 years), and the mean follow-up time was 3.9 years (range, 0.7-12.1 years). The primary outcome measure was the incidence of atrophic lesions determined by fundus autofluorescence imaging; areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) were out­lined and quantified.

    At the 3-year mark, 24% of eyes that did not show DDAF on initial evaluation had developed a DDAF lesion. How­ever, by 5 years of follow-up, approx­imately 50% displayed the lesion. For eyes without DDAF initially, the medi­an time to develop a DDAF lesion was 4.9 years. Among eyes without QDAF on initial evaluation, the median time to QDAF occurrence was 6.3 years. Eyes with DDAF at the first visit were less likely than were those without DDAF to develop a QDAF lesion. The latter finding may imply that DDAF lesions grow over time but do not increase in number. In a forthcoming ProgStar study, incidence rates will be evaluated further, and structural and functional consequences will be identified.

    In conclusion, the authors said, the results augment knowledge about the natural course of Stargardt disease, and they added that the fact that many eyes developed DDAF in less than 5 years suggests that the incidence of DDAF may be an appropriate outcome measure for treatment trials. (Also see related commentary by Catherine Cukras, MD, PhD, and Brett G. Jeffrey, PhD, in the same issue.)

    The original article can be found here.