Researchers at the U.S. National Eye Institute (NEI) believe their adaptive optics indocyanine green (AO-ICG) imaging technique could be used to help diagnose and monitor the progression of eye diseases, and to preclinically detect cellular-level damage to the retinal pigment epithelium (RPE) by nondestructively charting changes in the fluorescent RPE mosaic over varying periods of time. Mosaic of retinal pigment epithelial cells, visualized with indocyanine green (ICG) and adaptive optics. Courtesy of Johnny Tam/U.S. National Eye Institute. The researchers are using in vivo fluorescence ophthalmoscopy and adaptive optics to capture mosaic patterns created by the RPE in human subjects. The RPE is a thin layer of cells below the photoreceptors (rods and cones) on the retina. It delivers nutrients to and removes cellular wastes from the photoreceptors; therefore, the health of the retina is very much linked to the health of the RPE. Unfortunately, the RPE is hard to image because the cells contain varying amounts of light-absorbing pigment and because optical aberrations created by the structure of the eye prevent resolution of the layer on a cellular level. To solve these problems, Johnny Tam and his NEI colleagues used a fluorescent dye (ICG) to make the highly pigmented RPE cells more visible to their imaging system, and employed AO technology to compensate for optical aberrations created by the eye. After validating their approach using mouse models, the researchers said that its AO-ICG system is capable of resolving individual RPE cells and capturing the fluorescent mosaic patterns they create. The next phase of the study involved testing the AO-ICG system on human eyes. The AO-ICG system consists of a custom-made multimodal AO retinal imager with a computer-controlled fixation system. Tam and his team said the system has a lateral resolution of 2 to 3 µm and a 0.23- to 0.60-mm field of view on the retina. In a proof-of-concept study, the team observed that RPE patterns remained constant in individuals with healthy eyes, but changed over time in people with vision diseases linked to damaged RPEs. The researchers concluded that changes in the normally static fluorescent RPE mosaics could someday be used to track retinal disease onset and progression. The researchers first looked at the RPE mosaic patterns of five human subjects with healthy eyes. Six minutes after ICG was injected intravenously, the fluorescence signal from the subjects’ RPE cells became stable and remained visible for hours. The total image-acquisition time for each eye ranged between 1 and 3 hours with built-in breaks for the patient.