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Title: Assessment of retinal structure and function in Stargardt disease using in-depth advanced phenotyping in preparation for therapeutic intervention
Author: Tanna, Preena
ISNI:       0000 0004 7965 0419
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Stargardt disease (STGD1; MIM 248200) is the most common inherited macular dystrophy in both adults and children. STGD1 is the most prevalent single gene disorder causing blindness and one of the commonest causes of inherited childhood and adulthood visual impairment. This natural history study established a panel of 85 well-characterised molecularly confirmed patients with STGD1 including patients with childhood-onset and adult-onset STGD1. Retinal structure was investigated using spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and adaptive optics scanning light ophthalmoscopy (AOSLO). Retinal function was investigated using visual acuity, contrast sensitivity, full-field static perimetry, and microperimetry. Reliable and sensitive metrics were established for application in natural history studies, clinical practice, and therapeutic intervention. Using SD-OCT imaging to investigate the quantification of ellipsoid zone (EZ) loss, measuring the area of EZ loss was more sensitive compared with transverse EZ loss measurements in children. AOSLO imaging showed that split-detection (non-confocal) AOSLO significantly improved the reliability and repeatability of cone density measurements compared with confocal AOSLO. In addition, volumetric indices of retinal function provided a reliable measure of change in retinal sensitivity which is an alternative to mean sensitivity when summarizing static perimetry data to a single outcome measure. However, both best corrected visual acuity and contrast sensitivity testing were found to be insensitive to small changes; and that quantitative assessments are needed to determine a reliable metric for FAF imaging. Interocular structural and functional symmetry was consistently observed in the vast majority of patients and the rate of change for this cohort was reported which provided valuable information on the natural progression of the disease. This study included the largest cohort of children to date who showed a highly variable rate of change of the disease, with highly progressive disease from early childhood, suggesting the importance of analysing children and adults independently. Given that patients with earlier onset typically present with a severe and rapidly progressive phenotype, children may be ideal candidates for clinical trials both in 4 terms of rapid readouts and also potentially deriving the most benefit. The observations in this study will be valuable for both clinical practice as well as for the optimal design of human clinical trials.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available