The Effect of Age on Optic Nerve Axon Counts, SDOCT Scan Quality, and Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in Rhesus Monkeys.

PURPOSE To evaluate the effect of age on optic nerve axon counts, spectral-domain optical coherence tomography (SDOCT) scan quality, and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in healthy monkey eyes. METHODS In total, 83 healthy rhesus monkeys were included in this study (age range: 1.2-26.7 years). Peripapillary RNFLT was measured by SDOCT. An automated algorithm was used to count 100% of the axons and measure their cross-sectional area in postmortem optic nerve tissue samples (N = 46). Simulation experiments were done to determine the effects of optical changes on measurements of RNFLT. An objective, fully-automated method was used to measure the diameter of the major blood vessel profiles within each SDOCT B-scan. RESULTS Peripapillary RNFLT was negatively correlated with age in cross-sectional analysis (P < 0.01). The best-fitting linear model was RNFLT(μm) = -0.40 × age(years) + 104.5 μm (R2 = 0.1, P < 0.01). Age had very little influence on optic nerve axon count; the result of the best-fit linear model was axon count = -1364 × Age(years) + 1,210,284 (R2 < 0.01, P = 0.74). Older eyes lost the smallest diameter axons and/or axons had an increased diameter in the optic nerve of older animals. There was an inverse correlation between age and SDOCT scan quality (R = -0.65, P < 0.0001). Simulation experiments revealed that approximately 17% of the apparent cross-sectional rate of RNFLT loss is due to reduced scan quality associated with optical changes of the aging eye. Another 12% was due to thinning of the major blood vessels. CONCLUSIONS RNFLT declines by 4 μm per decade in healthy rhesus monkey eyes. This rate is approximately three times faster than loss of optic nerve axons. Approximately one-half of this difference is explained by optical degradation of the aging eye reducing SDOCT scan quality and thinning of the major blood vessels. TRANSLATIONAL RELEVANCE Current models used to predict retinal ganglion cell losses should be reconsidered.