{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:52:56Z","timestamp":1785919976575,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>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 \u00b5m in Control eyes, 86.3 \u00b5m in MSnoON eyes, and 69.5 \u00b5m in MS+ON eyes. After 15 years, the values were 88.5 \u00b5m, 80.8 \u00b5m, and 59.5 \u00b5m, respectively. Intragroup comparisons between 2010 and 2025 showed statistically significant reductions in pRNFL thickness across all three groups (Wilcoxon test, p &lt; 0.05). Intergroup comparisons revealed significant differences among the three groups at both time points (Mann\u2013Whitney test, p &lt; 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.<\/jats:p>","DOI":"10.3390\/jcm15156072","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:42:36Z","timestamp":1785850956000},"page":"6072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fifteen-Year Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-5474","authenticated-orcid":false,"given":"Francisco","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Service of Ophthalmology and IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"CIMUS and Department of Surgery and Medico-Surgical Specialties, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-5923","authenticated-orcid":false,"given":"Diego","family":"de Dios","sequence":"additional","affiliation":[{"name":"Service of Ophthalmology and IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Manuel","family":"Abalo-Lojo","sequence":"additional","affiliation":[{"name":"Service of Ophthalmology and IDIS, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"CIMUS and Department of Surgery and Medico-Surgical Specialties, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1212\/01.wnl.0000250267.85698.7a","article-title":"Gray matter involvement in multiple sclerosis","volume":"68","author":"Pirko","year":"2007","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100977","DOI":"10.1016\/j.lanepe.2024.100977","article-title":"Multiple sclerosis: Emerging epidemiological trends and redefining the clinical course","volume":"44","author":"Portaccio","year":"2024","journal-title":"Lancet Reg. 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