What is the growth rate of atrophic lesions in patients with Stargardt disease?
In this multicenter cohort study, mean progression of definitely decreased autofluorescence lesions was 0.51 mm2/y, and of total decreased fundus autofluorescence was 0.35 mm2/y. Rates of progression depended on initial lesion size.
The growth rate of atrophic lesions as determined by fundus autofluorescence in patients with Stargardt disease may be a suitable outcome measure for treatment trials.
Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease.
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.
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.
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.
Rupert W. Strauss, Beatriz Muñoz, Alexander Ho, Anamika Jha, Michel Michaelides, Artur V. Cideciyan, Isabelle Audo, David G. Birch, Amir H. Hariri, Muneeswar G. Nittala, SriniVas Sadda, Sheila West, Hendrik P. N. Scholl, . Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9). JAMA Ophthalmol. 2017;135(11):1232–1241. doi:10.1001/jamaophthalmol.2017.4152