Progression of Late-Onset Stargardt Disease
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 progre...
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
Association for Research in Vision and Ophthalmology
2016
|
| _version_ | 1826300902112231424 |
|---|---|
| author | Lambertus, S Lindner, M Bax, N Mauschitz, M Nadal, J Schmid, M Schmitz-Valckenberg, S Hollander, A Weber, B Holz, F van der Wilt, G Fleckenstein, M Hoyng, C Foveal sparing Atrophy Study Team (FAST) |
| author_facet | Lambertus, S Lindner, M Bax, N Mauschitz, M Nadal, J Schmid, M Schmitz-Valckenberg, S Hollander, A Weber, B Holz, F van der Wilt, G Fleckenstein, M Hoyng, C Foveal sparing Atrophy Study Team (FAST) |
| author_sort | Lambertus, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:24:12Z |
| format | Journal article |
| id | oxford-uuid:dffdb8f1-3cb6-49ce-8762-30393c2ecea6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:24:12Z |
| publishDate | 2016 |
| publisher | Association for Research in Vision and Ophthalmology |
| record_format | dspace |
| spelling | oxford-uuid:dffdb8f1-3cb6-49ce-8762-30393c2ecea62022-03-27T09:43:29ZProgression of Late-Onset Stargardt DiseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dffdb8f1-3cb6-49ce-8762-30393c2ecea6EnglishSymplectic Elements at OxfordAssociation for Research in Vision and Ophthalmology2016Lambertus, SLindner, MBax, NMauschitz, MNadal, JSchmid, MSchmitz-Valckenberg, SHollander, AWeber, BHolz, Fvan der Wilt, GFleckenstein, MHoyng, CFoveal sparing Atrophy Study Team (FAST)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. |
| spellingShingle | Lambertus, S Lindner, M Bax, N Mauschitz, M Nadal, J Schmid, M Schmitz-Valckenberg, S Hollander, A Weber, B Holz, F van der Wilt, G Fleckenstein, M Hoyng, C Foveal sparing Atrophy Study Team (FAST) Progression of Late-Onset Stargardt Disease |
| title | Progression of Late-Onset Stargardt Disease |
| title_full | Progression of Late-Onset Stargardt Disease |
| title_fullStr | Progression of Late-Onset Stargardt Disease |
| title_full_unstemmed | Progression of Late-Onset Stargardt Disease |
| title_short | Progression of Late-Onset Stargardt Disease |
| title_sort | progression of late onset stargardt disease |
| work_keys_str_mv | AT lambertuss progressionoflateonsetstargardtdisease AT lindnerm progressionoflateonsetstargardtdisease AT baxn progressionoflateonsetstargardtdisease AT mauschitzm progressionoflateonsetstargardtdisease AT nadalj progressionoflateonsetstargardtdisease AT schmidm progressionoflateonsetstargardtdisease AT schmitzvalckenbergs progressionoflateonsetstargardtdisease AT hollandera progressionoflateonsetstargardtdisease AT weberb progressionoflateonsetstargardtdisease AT holzf progressionoflateonsetstargardtdisease AT vanderwiltg progressionoflateonsetstargardtdisease AT fleckensteinm progressionoflateonsetstargardtdisease AT hoyngc progressionoflateonsetstargardtdisease AT fovealsparingatrophystudyteamfast progressionoflateonsetstargardtdisease |