Normative adaptive optics retinal imaging reveals age and sex dependent differences in cone photoreceptor diameter

Abstract

Purpose : Adaptive Optics (AO) retinal imaging enables in vivo high-resolution images of cells such as cone photoreceptors. Although cone density and spacing have been widely reported as metrics for evaluating cones, currently, quantitative assessment of cone diameters in larger datasets is limited. In this study, we present a normative database of in vivo human cone diameter evaluated across eccentricity, age, and sex.

Methods : Non-confocal split detection AO imaging was performed in 24 eyes of 24 healthy subjects (13 females and 11 males; mean±SD 42±18 years, ranging from 12-73 years). Subjects were classified into seven age brackets: 12-19 years (n=3, 13%), 20-29 (n=4, 17%), 30-39 (n=4, 17%), 40-49 (n=4, 17%), 50-59 (n=4, 17%), 60-69 (n=3, 13%), and 70-79 (n=2, 8%). Regions of interest (ROI, n=217) from the AO images were obtained from near the fovea (based on visibility of cones on non-confocal split detection) to 6 mm eccentricity. Cone photoreceptors were segmented for diameter measurements by expert graders assisted by a custom artificial intelligence algorithm (PMID 33507868).

Results : Cone diameter increased with increasing eccentricity across both age and sex (n=15739 segmented cones), from an average of 4.94 µm (eccentricity: 1 mm) to 7.77 µm (6 mm). There was a significant difference between the seven age groups across eccentricity (P<0.05). In general, cone diameters in younger subjects were larger than those from older subjects near the fovea, with smaller age-related differences observed at increasing eccentricities. In addition, cone diameter in females was slightly greater (by an average of 5%) than cone diameter in males across the range of eccentricities measured (P<0.05). The differences in cone diameter between females and males could not be accounted for by differences in axial length (P=0.28) or age (P=0.18).

Conclusions : Normative in-vivo human cone diameter data is an important first step towards future comparisons with diseased eyes. As expected, cone diameter increases as a function of retinal eccentricity. However, both age and sex dependent changes were observed, which may have implications for future studies.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.