Estimated Rates of Retinal Ganglion Cell Loss with Aging

Purpose: To evaluate the effect of aging on estimated retinal ganglion cell (RGC) counts over time in healthy eyes, obtained from a combination of structural and functional information. Design: Longitudinal observational cohort study. Participants: One hundred healthy eyes of 50 subjects. Methods: Estimated RGC counts were obtained by a previously described method using standard automated perimetry sensitivity thresholds and OCT retinal nerve fiber layer thickness measurements. Linear mixed- effects models were applied to investigate the effect of aging, as well as other covariates, on rates of change in estimated RGC counts over time. Main Outcome Measures: Rates of change in estimated RGC counts in healthy eyes. Results: Subjects had a mean age of 49.6 +/- 15.7 years at baseline (range 22.8-89.9 years) and were followed up for 3.5 +/- 2.5 years. Thirty-three (66%) patients were female and 11(22%) self-identified as Black. At baseline, the eyes had an average estimated RGC count of 1 144 010 +/- 222 084 cells. After adjusting for confounding factors, the mean rate of change in estimated RGC counts was-6769 RGC/year (95% confidence interval:-10 994 to-2544 RGC/year; P = 0.002), or 0.6%/year. Older age and longer axial length were significantly associated with lower RGC counts at baseline. Conclusions: A significant age-related decline in estimated RGC counts was found in healthy subjects with a combined metric integrating imaging and functional testing. The estimated mean age-related decline was remarkably similar to estimates from previous histologic studies in cadaver eyes, reinforcing the validity of the proposed combined metric and highlighting the importance of considering age when evaluating RGC count changes over time for monitoring glaucoma progression. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2025;5:100616 (c) 2024 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).