Photoreceptor-Based Biomarkers in AOSLO Retinal Imaging

Improved understanding of the mechanisms underlying inherited retinal degenerations has created the possibility of developing much needed treatments for these relentless, blinding diseases. However, standard clinical indicators of retinal health (such as visual acuity and visual field sensitivity) are insensitive measures of photoreceptor survival. In many retinal degenerations, significant photoreceptor loss must occur before measurable differences in visual function are observed. Thus, there is a recognized need for more sensitive outcome measures to assess therapeutic efficacy as numerous clinical trials are getting underway. Adaptive optics (AO) retinal imaging techniques correct for the monochromatic aberrations of the eye and can be used to provide nearly diffraction-limited images of the retina. Many groups routinely are using AO imaging tools to obtain in vivo images of the rod and cone photoreceptor mosaic, and it now is possible to monitor photoreceptor structure over time with single cell resolution. Highlighting recent work using AO scanning light ophthalmoscopy (AOSLO) across a range of patient populations, we review the development of photoreceptor-based metrics (e.g., density/geometry, reflectivity, and size) as candidate biomarkers. Going forward, there is a need for further development of automated tools and normative databases, with the latter facilitating the comparison of data sets across research groups and devices. Ongoing and future clinical trials for inherited retinal diseases will benefit from the improved resolution and sensitivity that multimodal AO retinal imaging affords to evaluate safety and efficacy of emerging therapies.