Progression of Late-Onset Stargardt Disease
| Autor: | Lambertus, S, Lindner, M, Bax, NM, Mauschitz, MM, Nadal, J, Schmid, M, Schmitz-Valckenberg, S, den Hollander, AI, Weber, BH, Holz, FG, van der Wilt, GJ, Fleckenstein, M, Hoyng, CB, Foveal sparing Atrophy Study Team (FAST) |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology Visual acuity Time Factors DNA Mutational Analysis Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] Visual Acuity 610 Medizin ABCA4 Sensory disorders Radboud Institute for Health Sciences [Radboudumc 12] Retinal Pigment Epithelium Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Macular Degeneration 0302 clinical medicine Medicine Stargardt Disease Fluorescein Angiography Aged 80 and over ddc:610 biology Middle Aged Phenotype Disease Progression Female medicine.symptom Tomography Optical Coherence Cohort study medicine.medical_specialty Fundus Oculi Late onset 03 medical and health sciences Atrophy Ophthalmology Electroretinography Humans Aged Retrospective Studies business.industry Retrospective cohort study DNA medicine.disease Confidence interval eye diseases Stargardt disease 030104 developmental biology Mutation 030221 ophthalmology & optometry biology.protein 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 ATP-Binding Cassette Transporters business Follow-Up Studies |
| Zdroj: | Investigative Ophthalmology and Visual Science, 57, 5186-5191 Investigative Ophthalmology and Visual Science, 57, 13, pp. 5186-5191 |
| ISSN: | 0146-0404 |
| DOI: | 10.5283/epub.35112 |
| Popis: | Contains fulltext : 168075.pdf (Publisher’s version ) (Open Access) 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|