Analysis of age-related changes in cone cell spacing and density at the fovea centralis in healthy adults and their influencing factors

Objective  To investigate the changes in the spacing and density of foveal cone cells in healthy adults with age, as well as their spatial distribution characteristics, and to investigate the influencing factors.

Methods  A cross-sectional study was conducted. A total of 106 healthy individuals (106 eyes) who underwent routine physical examinations at the Physical Examination Center of Beijing Tongren Hospital, Capital Medical University from August 2024 to March 2025 were recruited. They were divided into groups according to age: 26 eyes in the 18-30 years old group, 20 eyes in the 31-40 years old group, 23 eyes in the 41-50 years old group, 22 eyes in the 51-60 years old group, and 15 eyes in the >60 years old group. Subsequently, the age groups without significant changes of cone cell spacing and density were merged as 46 eyes in the 18-40 years old group, 45 eyes in the 41-60 years old group, and 15 eyes in the >60 years old group. All subjects underwent vision, refraction, intraocular pressure, and slit-lamp microscope examinations. Meanwhile, macular fundus images and cone cell images in the foveal area were obtained by confocal scanning laser ophthalmoscopy. The cone cell spacing (D1, D2, D3) and density (CD1, CD2, CD3) within the 1.7°×1.7°, 3.4°×3.4°, and 5.1°×5.1° macular visual fields were measured. The changes in foveal cone cell parameters among different age groups were compared. The correlations among cone cell density and spacing in different macular foveal visual fields and age were analyzed. The effects of age, sex, intraocular pressure, and spherical equivalent (SE) on cone cell parameters were evaluated by multiple linear regression analysis. This study followed the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No. TREC2025-KY024). Written informed consent was obtained from all subjects.

Results  For all subjects, D1, D2, and D3 were (9.56±1.20), (10.02±1.25), and (10.27±1.27) μm, respectively, and CD1, CD2, and CD3 were 17 421 (14 167, 20 555), 15 808 (13 159, 18 359), and 14 788 (12 587, 17 479) cells/mm ^2, respectively, showing statistically significant overall differences ( F=4.382, P=0.003; H=17.075, P=0.002). Among them, D2 and D3 were higher than D1, D3 was higher than D2, CD2 and CD3 were lower than CD1, and CD3 was lower than CD2, with statistically significant differences (all P<0.05). In the 41-50 years old group, 51-60 years old group, and >60 years old group, D1, D2, and D3 were higher, and CD1, CD2, and CD3 were lower than those in the 18-30 years old group, with statistically significant differences (all P<0.05). D1, D2, and D3 were higher, and CD1, CD2, and CD3 were lower in the >60 years old group than those in the 31-40 years old group and 41-50 years old group, with statistically significant differences (all P<0.05). After merging the age groups, D1, D2, and D3 in the 41-60 years old group and the >60 years old group were higher, and CD1, CD2, and CD3 were lower than those in the 18-40 years old group, with statistically significant differences (all P<0.05). The D3 was higher, and CD1, CD2, and CD3 were lower in the >60 years old group than in the 41-60 years old group, with statistically significant differences (all P<0.05). D1, D2, and D3 were highly negatively correlated with CD1, CD2, and CD3, respectively ( r _s=-0.997, -0.997, -0.997; all P<0.001). Age was moderately positively correlated with D1, D2, and D3 ( r=0.438, 0.421, 0.445; all P<0.001), and moderately negatively correlated with CD1, CD2, and CD3 ( r _s=-0.431, -0.420, -0.445; all P<0.001). Multiple linear regression analysis showed that age was the main influencing factor for cone cell spacing and cone cell density, SE was the secondary influencing factor, while sex and intraocular pressure were not influencing factors.

Conclusions  In healthy adults, from the center to the periphery of the fovea, the distribution of cone cells shows that the cone cell spacing gradually increases and the cone cell density gradually decreases. With the increase of age, the cone cell spacing gradually increases, and the cone cell density gradually decreases, and the changes become significant from the ages of 40 and 60. Besides age, cone cell parameters are also related to SE; that is, as SE drifts towards myopia, the cone cell spacing increases and the cone cell density decreases.