Associations of Optic Nerve Head and Parapapillary Atrophy Changes With Retinal Nerve Fiber Layer and Ganglion Cell Complex Thinning in Healthy Eyes

Purpose: To determine whether retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning occurs in association with changes in the optic nerve head (ONH) and parapapillary atrophy (PPA) over five years’ follow-up. Methods: This longitudinal observational study recruited participants aged ≥50 years. Participants were classified into ONH/PPA changed and ONH/PPA unchanged groups based on changes in ONH shape, the position of retinal vessels, and PPA morphology. Changes in RNFL and GCC were compared between the two subgroups. Linear regression models were used to evaluate the associations between changes in RNFL and GCC thickness and both ocular and systemic factors. Results: A total of 149 healthy eyes were included. During the five-year follow-up period, both RNFL and GCC thickness exhibited significant thinning. Specifically, the RNFL thinned by 1.59 µm, and the GCC thinned by 1.11 µm. Significant differences were observed in the change of the inferior RNFL between the two subgroups (Padj = 0.044), whereas no statistically significant differences were found for other parameters. The change in inferior RNFL was independently associated with baseline axial length (AL) (P = 0.025), change in AL (P = 0.003), change in disc area (P < 0.001) and change in ONH/PPA (P = 0.045); whereas the change in average GCC was not significantly associated with any of the evaluated parameters. Conclusions: Significant longitudinal changes in RNFL and GCC thickness were observed in healthy eyes. GCC parameters appear to be unrelated to morphological changes of the ONH and PPA, which may facilitate the early detection of glaucoma and its progression in individuals with age-related ONH/PPA alterations. Translational Relevance: This study provides clinicians with a key insight: GCC parameters may offer greater clinical utility than RNFL parameters for detecting early glaucoma and monitoring disease progression in individuals with age-related structural alterations of the ONH and PPA region.