{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T08:14:11Z","timestamp":1783498451545,"version":"3.55.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Austrian MS Research Society"},{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Retinal layer thinning is associated with disability progression and treatment failure in relapsing multiple sclerosis (RMS). However, the systematic integration of optical coherence tomography (OCT)-derived metrics into a composite measure of treatment response has not yet been evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed two observational cohorts of patients with RMS who newly initiated DMT, received an MRI and OCT at baseline and 12\u00a0months, and had\u2009\u2265\u200924\u00a0months of clinical follow-up. No evidence of disease activity (NEDA-3\/NEDA-3\u2009+\u2009OCT) status was assigned at 12\u00a0months after DMT. Retinal thinning was defined as a reduction of\u2009\u2265\u20091.0\u00a0\u00b5m\/year peripapillary retinal nerve fiber layer or\u2009\u2265\u20090.5\u00a0\u00b5m\/year ganglion-cell\/inner plexiform layer. The primary endpoint was confirmed disability progression occurring after the 12\u00a0month NEDA assessment. Both low-efficacy DMT and high-efficacy were included and analyzed jointly, with treatment class entered as a covariate in all models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 124 individuals (72% female, mean age 33.1 [SD\u2009\u00b1\u20097.7]\u00a0years, median EDSS of 2.0 [IQR 0.0\u20132.5]) were included. Over a median follow-up period of 3.4\u00a0years, disability progression was observed in 28 (23%) individuals.<\/jats:p>\n                    <jats:p>Time to and risk of disability progression did not significantly differ between EDA-3 and NEDA-3 (restricted mean survival time [RMST]: 43.4 [SE\u2009\u00b1\u20092.8] vs. 48.1 [SE\u2009\u00b1\u20091.3] months, p\u2009=\u20090.067; adjusted hazard ratio [aHR] 1.52, 95% LL-CI 0.64, p\u2009=\u20090.173). When retinal layer thinning was incorporated, EDA-3\u2009+\u2009OCT was associated with a higher risk of future progression (aHR 6.59, 95% LL-CI 2.38, p\u2009=\u20090.005) and shorter time to progression (RMST: 41.9 [SE\u2009\u00b1\u20092.1] vs. 51.9 [SE\u2009\u00b1\u20090.9] months, p\u2009&lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Incorporating retinal layer thinning into the NEDA-3 framework substantially improves prediction of subsequent disability progression compared with conventional NEDA-3 alone, identifying a subgroup of patients in whom ongoing neurodegeneration appears to drive disability accumulation despite suppressed inflammatory activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13909-8","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:03:36Z","timestamp":1780977816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integration of retinal layer thinning into NEDA-3 predicts disability progression in multiple sclerosis"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7970-5349","authenticated-orcid":false,"given":"Fabian","family":"F\u00f6ttinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nik","family":"Krajnc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Berek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Philipp","family":"Nolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Heinrich","family":"Schmidauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Di Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kornek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Leutmezer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Macher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Monschein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Ponleitner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulus","family":"Rommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Schmied","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Zebenholzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Zulehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Zrzavy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Deisenhammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"Pemp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Hegen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-0851","authenticated-orcid":false,"given":"Gabriel","family":"Bsteh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"issue":"10422","key":"13909_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/s0140-6736(23)01473-3","volume":"403","author":"D Jakimovski","year":"2024","unstructured":"Jakimovski D, Bittner S, Zivadinov R et al (2024) Multiple sclerosis. 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Nik Krajnc: has participated in meetings sponsored by, received speaker honoraria or travel funding from Alexion, BMS\/Celgene, Janssen-Cilag, Merck, Novartis, Roche and Sanofi and held a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Klaus Berek: has participated in meetings sponsored by and received travel funding or speaker honoraria from Roche, Teva, Merck, Biogen, Sanofi and Novartis. He is associate editor of Frontiers in Immunology \/ Neurology, Section Multiple Sclerosis and Neuroimmunology and member of the editorial board of Neurology International. Jan Philipp Nolte: has participated in meetings sponsored by, received speaker honoraria or travel funding from Novartis and Biogen. Martin Heinrich Schmidauer: has participated in meetings sponsored by or received travel grants from Novartis, Sanofi-Genzyme, and Amgen. Franziska Di Pauli: has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Biogen, Celgene BMS, Horizon, Janssen-Cilag, Merck, Neuraxpharm, Novartis, Sandoz, Sanofi, Teva, and Roche. Her institution has received research grants from Roche. Barbara Kornek: has received honoraria for speaking and for consulting from Biogen, BMS, Johnson&Johnson, Merck, Novartis, Roche, Teva and Sanofi outside of the submitted work. No conflict of interest with respect to the present study. Fritz Leutmezer: has participated in meetings sponsored by, received speaker honoraria or travel funding from Actelion, Almirall, Biogen, Celgene, Johnson&Johnson, MedDay, Merck, Novartis, Roche, Sanofi and Teva, and received honoraria for consulting Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva. Stefan Macher: declares no conflict of interest relevant to this study. Tobias Monschein: has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, BMS\/Celgene, Merck, Novartis, Roche, Sanofi and Teva. Markus Ponleitner: Has received speaker or consulting honoraria from Amicus, Sanofi-Aventis, and Novartis and participated in meetings sponsored by and received travel funding from Amicus, Merck, Novartis, and Sanofi-Genzyme, as well as grants for clinical, research, and exchange fellowships awarded by the European Academy of Neurology (EAN) and the Austrian Society of Neurology. Paulus Rommer: has received honoraria for consultancy\/speaking from Alexion\/Astra Zeneca, Allmiral, Amgen\/Horizon, Amicus, Biogen, Merck, Novartis, Roche, Sandoz, and Sanofi. He has received research grants from Amicus, Biogen, Merck, Roche, and Austria Science Funds (FWF). Christiane Schmied: declares no conflict of interest relevant to this study. Karin Zebenholzer: received speaking honoraria or travel grants from Biogen, Celgene\/BMS, Novartis and Sanofi. Gudrun Zulehner: has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi and Teva. Tobias Zrzavy: has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi and Teva. Florian Deisenhammer: has participated in meetings sponsored by or received honoraria for acting as an advisor\/speaker for Alexion, Almirall, Biogen, BMS, Sanofi, Amgen, Janssen, Laurea Group, Medwhizz, Merck, Novartis Pharma, Neuraxpharm, Roche, Sandoz, and Teva. His institution has received research grants from Biogen, Novartis Pharma, and Sanofi. He is review editor of Frontiers Neurology. Thomas Berger: has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, BMS, Eisai, Genesis, GSK, Jazz Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Neuraxpharm, Newbridge, Novartis, Octapharma, Roche, Sandoz, Sanofi, Teva, TG Therapeutics and UCB. His institution has received financial support in the past 12\u00a0months by unrestricted research grants (Biogen, Bayer, BMS, Merck, Novartis, Roche, Sanofi, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi, Teva. Berthold Pemp: has received honoraria for consulting from Novartis, has received honoraria for advisory boards\/consulting from Chiesi and GenSight, and has received speaker honoraria from Novartis, Chiesi and Santen. Harald Hegen: has participated in meetings sponsored by, received speaker honoraria or travel funding from Alexion, Amgen, Bayer, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Bristol Myers Squibb, Novartis, Roche, Sanofi-Genzyme, and Teva. His institution received research grants from Amgen and Novartis. Gabriel Bsteh: has received travel funding from Biogen, Merck, Novartis, Roche, Sanofi, and Teva; has received speaker honoraria from Biogen, BMS, Heidelberg Engineering, Janssen, Lilly, Medwhizz, Merck, Neuraxpharm, Novartis, Roche, Sanofi, Teva and Zeiss; has received honoraria for consulting Adivo Associates, Biogen, BMS, Janssen, Merck, Novartis, Roche, Sanofi and Teva. He has received unrestricted research grants from BMS, Merck and Novartis. He serves as the President\/CEO of the Austria Multiple Sclerosis Innovation Alliance (AMSIA) and the Head of the Austrian Multiple Sclerosis Cohort (AMSC) Steering Committee. He serves on the Executive Committee of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Board of Directors of the International Multiple Sclerosis VisualSystem Consortium (IMSVISUAL).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was approved by the ethics committees of the MedicalUniversity Vienna (ethical approval number: 1378\/2020) and the Medical University of Innsbruck (ethical approvalnumber: AM3743-281\/4.3).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"382"}}