Fifteen-Year Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis.

Background/Objectives: To evaluate changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with multiple sclerosis (MS) and healthy controls over a 15-year period. Methods: This is a retrospective, observational, longitudinal, case-control study. The study included 53 patients with relapsing-remitting MS and 44 age-matched healthy controls. pRNFL thickness was measured using optical coherence tomography (OCT) at baseline (2010) and 15 years later (2025) across 12 peripapillary sectors. Eyes were categorized into three groups: healthy control eyes (Control), eyes from MS patients without a history of optic neuritis (MSnoON), and eyes from MS patients with a history of optic neuritis (MS+ON). Median and interquartile range (IQR) were used for descriptive statistics. Non-parametric tests were applied for statistical analysis. Results: At baseline, the median pRNFL thickness was 94.8 µm in Control eyes, 86.3 µm in MSnoON eyes, and 69.5 µm in MS+ON eyes. After 15 years, the values were 88.5 µm, 80.8 µm, and 59.5 µm, respectively. Intragroup comparisons between 2010 and 2025 showed statistically significant reductions in pRNFL thickness across all three groups (Wilcoxon test, p < 0.05). Intergroup comparisons revealed significant differences among the three groups at both time points (Mann-Whitney test, p < 0.05). In all cases, Control eyes exhibited the greatest pRNFL thickness, followed by MSnoON eyes, and then MS+ON eyes. pRNFL thinning was not uniform across all peripapillary sectors. In MSnoON eyes, the temporo-superior and infero-nasal sectors appeared more resistant to fiber loss, whereas in MS+ON eyes, all sectors demonstrated significant thinning. Conclusions: Significant pRNFL thinning occurs over time in both MS and healthy eyes. Eyes from MS patients, regardless of a history of optic neuritis, exhibited greater loss than healthy controls. Sectoral analysis suggests differential vulnerability among peripapillary regions. The relative differences between Control, MSnoON, and MS+ON eyes were maintained over a 15-year period.