We have measured the spatial density of cones and rods in eight whole-mounted human retinas, obtained from seven individuals between 27 and 44 years of age, and constructed maps of photoreceptor density and between-individual variability. The average human retina contains 4.6 million cones (4.08-5.29 million). Peak foveal cone density averages 199,000 cones/mm2 and is highly variable between individuals (100,000-324,000 cones/mm2). The point of highest density may be found in an area as large as 0.032 deg2. Cone density falls steeply with increasing eccentricity and is an order of magnitude lower 1 mm away from the foveal center. Superimposed on this gradient is a streak of high cone density along the horizontal meridian. At equivalent eccentricities, cone density is 40-45% higher in nasal compared to temporal retina and slightly higher in midperipheral inferior compared to superior retina. Cone density also increases slightly in far nasal retina. The average human retina contains 92 million rods (77.9-107.3 million). In the fovea, the average horizontal diameter of the rod-free zone is 0.350 mm (1.25 degrees). Foveal rod density increases most rapidly superiorly and least rapidly nasally. The highest rod densities are located along an elliptical ring at the eccentricity of the optic disk and extending into nasal retina with the point of highest density typically in superior retina (5/6 eyes). Rod densities decrease by 15-25% where the ring crosses the horizontal meridian. Rod density declines slowly from the rod ring to the far periphery and is highest in nasal and superior retina. Individual variability in photoreceptor density differs with retinal region and is similar for both cones and rods. Variability is highest near the fovea, reaches a minimum in the midperiphery, and then increases with eccentricity to the ora serrata. The total number of foveal cones is similar for eyes with widely varying peak cone density, consistent with the idea that the variability reflects differences in the lateral migration of photoreceptors during development. Two fellow eyes had cone and rod numbers within 8% and similar but not identical photoreceptor topography.

Primate cones maximally sensitive to short wavelength light (blue cones) have been previously identified by using indirect methods. We stained 7 wholemounted human retinas obtained from 6 female donors, using an affinity purified antibody to a 19 amino acid peptide sequence at the N‐terminus of blue opsin (Lerea et al., '89: Neuron 3:367–376), standard PAP immunocytochemistry, and controls. Cones were counted where all outer segments could be traced to inner segments and were measured where cells were well aligned vertically.We find that: (1) 7% of cones within 4 mm of the foveal center are labeled by antiblue opsin; (2) compared to neighboring red/green cones, blue cone inner segments are 10% taller, have a larger cross‐sectional diameter near the junction with the outer segment, and a smaller diameter near the external limiting membrane, resulting in a more cylindrical shape, (3) foveal blue cones are sparse, irregularly spaced, and missing in a zone about 100 μm (0.35°) in diameter near the site of peak cone density, (4) the highest densities of blue cones (> 2,000 cells/mm2) are found in a ring at 0.1–0.3 mm eccentricity, and (5) the shortest distances between neighboring cones are between blue and red/green cones, and the blue and red/green mosaics are statistically independent.These findings are consistent with psychophysical reports of foveal tritanopia and maximum sensitivity to blue light at 1° eccentricity. Blue cone spacing may limit resolution of the blue channel out to 20–30° eccentricity. The blue and red/green mosaics appear to be formed by separate processes.

Purpose To characterize the morphology, prevalence, and topography of subretinal drusenoid deposits (SDD), a candidate histological correlate of reticular pseudodrusen, with reference to basal linear deposit (BlinD), a specific lesion of age-related macular degeneration (AMD); to propose a biogenesis model for both lesions. Methods Donor eyes with median death-to-preservation of 2:40 hr were post-fixed in osmium tannic acid paraphenylenediamine and prepared for macula-wide high-resolution digital sections. Annotated thicknesses of 21 chorioretinal layers were determined at standard locations in sections through the fovea and the superior perifovea. Results In 22 eyes of 20 Caucasian donors (83.1 ± 7.7 years), SDD appeared as isolated or confluent drusenoid dollops punctuated by tufts of RPE apical processes and associated with photoreceptor perturbation. SDD and BlinD were detected in 85.0% and 90.0% of non-neovascular AMD donors, respectively. SDD was thick (median, 9.4 µm) and more abundant in perifovea than fovea (p<0.0001). BlinD was thin (median, 2.1 µm) and more abundant in fovea than perifovea (p<0.0001). Conclusion SDD and BlinD prevalence in AMD eyes are both high. SDD's organized morphology, topography, and impact on surrounding photoreceptors imply specific processes of biogenesis. Contrasting topographies of SDD and BlinD suggest relationships with differentiable aspects of rod and cone physiology, respectively. A 2-lesion, 2-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented.

The distribution of photoreceptors is known for only one complete human retina and for the cardinal meridians only in the macaque monkey retina. Cones can be mapped in computer-reconstructed whole mounts of human and monkey retina. A 2.9-fold range in maximum cone density in the foveas of young adult human eyes may contribute to individual differences in acuity. Cone distribution is radially asymmetrical about the fovea in both species, as previously described for the distribution of retinal ganglion cells and for lines of visual isosensitivity. Cone density was greater in the nasal than in the temporal peripheral retina, and this nasotemporal asymmetry was more pronounced in monkey than in human retina.

Digital maps of quantitative AF, cell density, and packing geometry provide metrics for cellular-resolution clinical imaging and model systems. The uncoupling of RPE LF content, cell number, and photoreceptor topography in aging challenges LF's role in AMD.