Imaging human retinal pigment epithelium cells using adaptive optics optical coherence tomography

Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, but are often compromised in ageing and major ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, and while biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. We present a novel method based on optical coherence tomography (OCT) equipped with adaptive optics (AO) that overcomes the associated technical obstacles. The method takes advantage of the 3D resolution of AO-OCT, but more critically sub-cellular segmentation and registration that permit organelle motility to be used as a novel contrast mechanism. With this method, we successfully visualized RPE cells and characterized their 3D reflectance profile in every subject and retinal location (3 degrees and 7 degrees temporal to the fovea) imaged to date. We have quantified RPE packing geometry in terms of cell density, cone-to-RPE ratio, and number of nearest neighbors using Voronoi and power spectra analyses. RPE cell density (cells/mm(2)) showed no significant difference between 3 degrees (4,892 +/- 691) and 7 degrees (4,780 +/- 354). In contrast, cone-toRPE ratio was significantly higher at 3 degrees (3.88 +/- 0.52:1) than 7 degrees (2.31 +/- 0.23:1). Voronoi analysis also showed most RPE cells have six nearest neighbors, which was significantly larger than the next two most prevalent associations: five and seven. Averaged across the five subjects, prevalence of cells with six neighbors was 51.4 +/- 3.58% at 3 degrees, and 54.58 +/- 3.01% at 7 degrees. These results are consistent with histology and in vivo studies using other imaging modalities.