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Prospective Cohort Study of Childhood-Onset Stargardt Disease: Fundus Autofluorescence Imaging, Progression, Comparison with Adulthood-Onset Disease, and Disease Symmetry

Georgiou, M; Kane, T; Tanna, P; Bouzia, Z; Singh, N; Kalitzeos, A; Strauss, RW; ... Michaelides, M; + view all (2019) Prospective Cohort Study of Childhood-Onset Stargardt Disease: Fundus Autofluorescence Imaging, Progression, Comparison with Adulthood-Onset Disease, and Disease Symmetry. American Journal of Ophthalmology 10.1016/j.ajo.2019.11.008. (In press). Green open access

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Abstract

Purpose To determine the reliability and repeatability of quantitative evaluation of areas of decreased autofluorescence (DAF) from fundus autofluorescence (FAF) images and track disease progression in children with Stargardt disease (STGD1), and investigate clinical and genotype correlations, disease symmetry and intra-familial variability. Design Prospective Cohort Study. Methods Children and adults with molecularly confirmed STGD1 (n=90) underwent longitudinal FAF imaging with subsequent semi-automated measurement of the area of DAF and calculation of the annual rate of progression. The age of disease onset was recorded for all subjects, as well as the electroretinography (ERG) group at baseline (n=86). Patients were grouped for analysis based on the age at baseline and age of onset, into children (n=56), adults with childhood-onset STGD1 (n=15), and adults with adulthood-onset (n=19). Fifty FAF images were selected randomly and analysed by two observers to evaluate repeatability and reproducibility. Differences between groups, interocular symmetry, genotype-phenotype correlations and intrafamilial variability were also investigated both for baseline measurements as well as progression rates. Results Visual acuity, molecular genetics, ERG group, FAF metrics and their correlations. Results Mean age of onset ± SD was 9.6 ± 3.4 years for childhood-onset (n=71) and 28.3 ± 7.8 years for adulthood-onset STGD1 (n=19). The intra-observer and inter-observer reliability of DAF quantification was excellent (ICC; 0.995 and 0.987). DAF area was symmetric between eyes and the mean rate of progression (SD) was 0.69 (0.72), 0.78 (0.48) and 0.40 (0.36) mm2/year for children, adults with childhood-onset, and adults with adulthood-onset disease respectively. Patients belonging to a group 3 ERG phenotype (generalised cone and rod dysfunction) had a significantly greater progression rate. Limited intrafamilial variability was observed. Conclusions This is the first large prospective study of FAF in a cohort of molecularly confirmed children with STGD1. DAF area quantification was highly reliable and may thereby serve as a robust structural end-point. A high rate of progression was observed in childhood-onset disease, making this subtype of STGD1 ideally suited to be considered for prioritisation in clinical trials.

Type: Article
Title: Prospective Cohort Study of Childhood-Onset Stargardt Disease: Fundus Autofluorescence Imaging, Progression, Comparison with Adulthood-Onset Disease, and Disease Symmetry
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ajo.2019.11.008
Publisher version: https://doi.org/10.1016/j.ajo.2019.11.008
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Fundus autofluorescence, FAF, retina, Stargardt disease, ABCA4, STGD1, clinical trials, endpoints, early-onset, childhood-onset
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10087690
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