Abstract
Adaptive optics scanning light ophthalmoscopy (AOSLO) allows non-invasive assessment of the cone photoreceptor mosaic. Confocal AOSLO imaging of patients with achromatopsia (ACHM) reveals an altered reflectivity of the remaining cone structure, making identification of the cells more challenging than in normal retinas. Recently, a "split-detector" AOSLO imaging method was shown to enable direct visualization of cone inner segments in patients with ACHM. Several studies have demonstrated gene replacement therapy effective in restoring cone function in animal models of ACHM and human trials have on the horizon, making the ability to reliably assess cone structure increasingly important. Here we sought to examine whether absolute estimates of cone density obtained from split-detector and confocal AOSLO images differed from one another and whether the inter- and intra-observer reliability is significantly different between these modes. These findings provide an important foundation for evaluating the role of these images as tools to assess the efficacy of future gene therapy trials.