High-Resolution Imaging in Stargardt Disease: Preliminary Observations In Preparation for Intervention

Abstract

Purpose: There is considerable well-documented inter-subject variability in Stargardt disease (STGD) in terms of age of onset, and both pattern and rate of degeneration. Because of this variability and the lack of robust natural history data, longitudinal deep phenotyping is needed to better characterise the disease process. Such studies will result in a better understanding of the cellular changes associated with each genotype, which is a prerequisite to planned therapies for STGD.

Methods: Eleven patients (ages 7 to 62) with molecularly confirmed STGD underwent examination and retinal imaging, including autofluorescence (AF) imaging, spectral domain optical coherence tomography (SDOCT), and confocal adaptive optics scanning light ophthalmoscopy (AOSLO). Serial imaging was undertaken over a period ranging between 3 months and 1 year. Retinal lamination was assessed using SDOCT, and AOSLO was used to probe integrity of the photoreceptor mosaic and assess qualitative changes in reflectance.

Results: Visual function (20/20 to 20/200) and structure were highly variable in the cohort, with no consistent age-dependence. At presentation, the oldest subject in the cohort with a foveal-sparing STGD phenotype had normal foveal architecture, both on SDOCT and AOSLO, with only subtle parafoveal inner segment ellipsoid layer mottling and minimal mosaic disruption. At one year, the parafoveal disruption had progressed, with the foveal region remaining intact. Four subjects had relatively intact foveal architecture, with a ring of parafoveal photoreceptor loss. The remaining subjects had a variable degree of foveal atrophy, and a variable residual degree of para-foveal photoreceptor structure on AOSLO. The youngest subject was followed at three-monthly intervals, with progressive loss of photoreceptors detected with AOSLO, and increased atrophy on SDOCT. Areas of increased AF correlated with atrophic zones on SDOCT and areas of photoreceptor loss on AOSLO.

Conclusions: High-quality serial photoreceptor mosaic imaging in STGD was able to detect progression in children as young as 7 years of age. Further longitudinal testing in larger cohorts of molecularly proven patients is necessary to identify patients who may be most suitable for intervention. This will also establish the natural history, rates of progression, and identify the most sensitive and accurate measures of treatment effect.

Keywords: 550 imaging/image analysis: clinical • 648 photoreceptors • 696 retinal degenerations: hereditary