Lambertus, Stanley and Lindner, Moritz and Bax, Nathalie M. and Mauschitz, Matthias M. and Nadal, Jennifer and Schmid, Matthias and Schmitz-Valckenberg, Steffen and den Hollander, Anneke I. and Weber, Bernhard H. F. and Holz, Frank G. and van der Wilt, Gert Jan and Fleckenstein, Monika and Hoyng, Carel B. (2016) Progression of Late-Onset Stargardt Disease. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57 (13). pp. 5186-5191. ISSN 0146-0404, 1552-5783
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VISUAL-ACUITY LOSS; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; FUNDUS AUTOFLUORESCENCE; FLAVIMACULATUS; QUANTIFICATION; PHENOTYPE; GENE; late-onset Stargardt; fundus autofluorescence; retinal pigment epithelium atrophy; biomarker; disease progression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2019 08:41 |
| Last Modified: | 08 Apr 2019 08:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4125 |
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