Longitudinal Imaging of Foveal Cone Structure in Congenital Achromatopsia

Abstract

Purpose: Achromatopsia (ACHM) is a disorder associated with absent or severely limited function and variably-disrupted structure in cone photoreceptors. In order to monitor the efficacy of gene therapy efforts in this condition, it will be necessary to quantitatively monitor cone structure over time in individual retinas. Here we demonstrate the use of split-detection adaptive optics scanning light ophthalmoscopy (AOSLO) to longitudinally evaluate foveal cone structure in patients with ACHM.

Methods: Seven subjects with genetically confirmed ACHM were recruited. Confocal and split-detector AOSLO and SD-OCT imaging were performed at baseline and 9-10 months later. Peak foveal cone density was determined by manually outlining the rod-free zone as seen on confocal imaging - a variably sized area between image sets - and marking cells in that region, then measuring 27x27μm areas centered on each pixel.

Results: One subject had outer retinal atrophy in the fovea preventing foveal analysis. Another had a corneal abrasion at the first examination that prevented imaging, though this resolved by the second visit, and in a third subject the foveal center was not captured with the split-detector method at the first visit. The remaining 4 subjects showed little variability of residual foveal cone structure between the baseline and follow up visit. The peak densities at baseline for these subjects were 19,204, 16,460, 8,230, and 21,948 cones/mm² and 15,089, 19,204, 5,487, and 26,063 cones/mm² on follow-up respectively. The change in density between visits corresponded to an average difference of 2.5 cones in the search window. The OCT images showed no change in phenotype between visits based on previously published grading criteria (Sundaram V, et al. Ophthalmology 2014;121:234-245).

Conclusions: Due to nystagmus this is a particularly challenging patient population in which to obtain reliable longitudinal measures of cone structure. Despite this, we have demonstrated that we can re-image the exact same photoreceptors over a 9-month follow-up period and that there does not appear to be substantial change in foveal cone structure. The ability to obtain repeated measurements of structure will allow sensitive monitoring of the biological response to treatment in these patients.