Imaging photoreceptor somas and their loss in disease in the living human eye

Adaptive optics (AO) ophthalmoscopes have been extensively used to study photoreceptors in the living human retina. However, imaging key components of these cells—specifically the soma and axon—remains challenging due to their extremely low reflectance. Imaging photoreceptor somas is of significant clinical interest because the soma houses the cell’s genetic material, which plays a key role in regulating cellular function and maintaining cell health. Here, we present a method based on AO-OCT imaging that, for the first time, reveals the three-dimensional (3D) mosaic of photoreceptor somas in healthy eyes and identifies alterations in these mosaics in eyes afflicted by retinitis pigmentosa, which is the most common inherited retinal degeneration causing irreversible vision loss. We achieve this by: (1) sequentially focusing the AO-OCT beam across the outer nuclear layer thickness, where photoreceptor somas locate; (2) computationally shaping the AO-OCT spectral interferogram to suppress sidelobes induced by the external limiting membrane signal; and (3) acquiring, registering and averaging thousands of volume images in 3D with subcellular accuracy. These steps dramatically improve image contrast-to-noise ratio and enable quantitative analysis of the 3D soma stacks. This advancement in imaging capability to assess individual photoreceptor somas should improve our understanding of disease pathophysiology, provide new biomarkers for early disease detection, and improve gene therapy outcomes by identifying patients and retinal regions with sufficient soma populations suitable for treatment.