Detailed Analysis of Intraretinal Layers and Their Correlation to Brain Structures in Normal Healthy Aging

Purpose: The purpose of this study was to investigate the relationships between intraretinal layer volumes and visual cortical thickness in healthy individuals and determine the influence of age on these associations. Methods: Fifty-three subjects were recruited. One eye per subject was imaged using optical coherence tomography (OCT) to quantify volumes of total retinal thickness (TRT), retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer nuclear layer (ONL), outer plexiform layer (OPL), and photoreceptor (PR) layer. Brain magnetic resonance imaging (MRI) was performed, and cortical thickness was quantified in 13 visual cortex regions using the Schaefer 2018 atlas. Results: TRT, RNFL, and GCIPL volumes were significantly correlated with cortical thickness in multiple visual regions (r = 0.34-0.59, all P < 0.05). These associations were largely attenuated after adjusting for age. In contrast, selected RNFL and INL associations remained significant after age adjustment. OPL, ONL, and PR layer showed no significant correlations with cortical thickness. PR layer volume increased with age (r = 0.38, P < 0.01), unlike the age-related thinning observed in other layers. Conclusions: Distinct retinal layers exhibit differential relationships with the visual cortex, with some associations predominantly mediated by age and selected RNFL and INL associations persisting independently of age. Translational Relevance: Distinguishing age-mediated from age-independent retinal-cortical relationships may help identify OCT-derived retinal measures that differentiate normal aging from cerebral pathology and support their investigation as noninvasive biomarkers of central nervous system (CNS) integrity.