Adaptive optics scanning light ophthalmoscopy (AOSLO) allows noninvasive
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, makingthe 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.