In-vivo classification of human cone photoreceptors reveals crystalline S-cone sub-mosaics in the central retina.

The topography of S-cones in the macula sets the neural constraints for coding the short-wavelength spectrum of color vision. We find that S-cones tile the central human retina with a non-random crystalline arrangement. This finding departs from previous studies, likely due to limited sampling. In 2 subjects we classified cones using Adaptive Optics Line-scan OCT and a bleaching stimulus of 660±10 nm. 8 ROIs per subject were classified at 1.5° and ~4° eccentricity across the 4 meridians. Numbers of total and S- cones per ROI spanned 541-3545 (mean: 1823) and 38-171 (mean: 99), respectively. We measured S-cone spacing in each ROI using the established method of Density Recovery Profile (DRP). To compare with random arrangement, we generated 1000 Monte Carlo (MC) simulations of each ROI such that its cone locations were maintained but locations of S-cones within it were randomized. We then measured the radius in units of inter-cone distance for which S-cone density was significantly lower than MC distributions, finding low density in a 1-cone radius in 13/16 ROIs (8/8 at 1.5°, p ≤ .037. 5/8 at 3.5°-4.5°, p ≤ .002), and up to a 2-cone radius in 12/16 ROIs (7/8 at 1.5°, p ≤ .002. 5/8 at 3.5°-4.5° p ≤ .003). Further experiments will include additional human subjects, ROIs at higher eccentricities, and classification using a short-wavelength bleach. Together, these findings have important implications for retinal development and color coding retinal circuits.