期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 57, 期 13, 页码 5186-5191出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.16-19833
关键词
late-onset Stargardt; fundus autofluorescence; retinal pigment epithelium atrophy; biomarker; disease progression
资金
- Stichting A.F. Deutman Researchfonds Oogheelkunde, Nijmegen, The Netherlands
- Nederlandse Oogonderzoek Stichting, Nijmegen, The Netherlands
- Deutsche Forschungsgemeinschaft, Bonn, Germany [FL 658/4-1, Ho1926/3-1]
- BONFOR GEROK Program, Faculty of Medicine, University of Bonn [O-137.0020]
- UitZicht: Stichting MD fonds
- Landelijke Stichting voor Blinden en Slechtzienden
- Oogfonds
PURPOSE. Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. METHODS. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset >= 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. RESULTS. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. CONCLUSIONS. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.
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