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However, no data exist on the relationship between OCT metrics and cognitive progression independent of relapse activity (cognitive PIRA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess if OCT can prognosticate cognitive PIRA events in pwMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective study with baseline OCT (peripapillary retinal nerve fiber- (pRNFL), macular ganglion cell-inner plexiform- (mGCIPL) and inner nuclear layers (mINL)) and brief international cognitive assessment for MS (BICAMS) at yearly visits. Cognitive PIRA in each test was defined as more than 10% decrease compared to previous visit (reference) and confirmed 12\u00a0months later (confirmation visit), without relapses 90\u00a0days before or 30\u00a0days after the event and confirmation visits. We employed Cox regression models adjusting for age, baseline cognitive test, education, and treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      98 pwMS followed for a median of 5\u00a0years (63% female, 81% relapsing\u2013remitting, age: 50.5\u2009\u00b1\u200911.6\u00a0years, median EDSS: 3.0). Each 1\u00a0\u00b5m increase in pRNFL thickness was associated with a 6% lower risk of Symbol Digit Modalities Test (SDMT) PIRA events (Hazard ratio (HR)\u2009=\u20090.94,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.027). Each 1\u00a0\u00b5m increase in mGCIPL thickness was associated with a 6% lower risk of Verbal Learning and Memory Test (VLMT) PIRA (HR\u2009=\u20090.94,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040). Each 1\u00a0\u03bcm increase in mINL thickness was associated with 20% lower risk of VLMT-PIRA (HR\u2009=\u20090.80,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030) and 50%\n                      <jats:italic>higher<\/jats:italic>\n                      risk of SDMT-PIRA events (HR\u2009=\u20091.50,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Retinal layers can be sensitive, patient-friendly prognostic markers of cognitive PIRA in pwMS.<\/jats:p>\n                  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Shaumya Sankar has nothing to disclose. Silvan Pless has nothing to disclose. Marc Stoessel has nothing to disclose. Lisa Hofer has nothing to disclose. Kean Schoenholzer received travel support by TEVA and AbbVie and is supported by the Swiss National Science Foundation (PZ00P3_216468). Shaumiya Sellathurai is supported by the Swiss National Science Foundation 514 (PZ00P3_216468). Federico Burguet Villena received travel support by TEVA and research grant (\u201cYoung talents in clinical research\u201d) by the Swiss Academy of Medical Sciences and of the G. & J. Bangerter-Rhyner Foundation. A. Cagol received speaker honoraria Novartis, Merck, and Roche. He is recipient of a Swiss Multiple Sclerosis Society Research grant (2025\/2026). Anastasios Demirtzoglou is an employee of the University Hospital and works for Neurostatus-UHB Ltd as an expert neurologist. Bettina Fischer-Barnicol contributed to an advisory board for Biogen and Merck. Marcus D' Souza is CEO of Neurostatus AG and has received travel support from Bayer AG, Biogen, Teva Pharmaceuticals, and Sanofi 520 Genzyme and research support from the University Hospital of Basel. Pasquale Calabrese has received honoraria for speaking at scientific meetings, serving at scientifc advisory boards, and consulting activities from: Abbvie, Actelion, Almirall, Bayer-Schering, Biogen Idec, Celgene, EISAI, Genzyme, Lundbeck, Merck Serono, Novartis, Pfzer, Teva, and Sanof-Aventis. His research is also supported by the Swiss Multiple Sclerosis Society and the Swiss National Research Foundation. Pascal Benkert has nothing to disclose. Jannis M\u00fcller received funding from the Swiss National Science Foundation (Grant No. P500PM214230 and P5R5PM225288) and the \u201cPool f\u00fcr Innere Medizin\u201d of the University Hospital Basel, outside the presented work. Konstantin Gugleta: Advisory Boards: AbbVie, AZAD, Santen. Research support: Swiss National Science Foundation. Tobias Derfuss received speaker fees, research support, travel support, and\/or served on Advisory Boards or Steering Committees of Alexion, Biogen, Celgene, GeNeuro, MedDay, Merck, Novartis, Roche and Sanofi-Genzyme; he received research support from Alexion, Biogen, Novartis, Roche, Swiss National Research Foundation, University of Basel, and Swiss MS Society. Cristina Granziera: The University Hospital Basel (USB), as the employer of Cristina Granziera has received the following fees which were used exclusively for research support: (1) advisory board and consultancy fees from Actelion, Novartis, Genzyme, and F. Hoffmann-La Roche; (2) speaker fees from Biogen and Genzyme-Sanofi; (3) research support from F. Hoffmann-La Roche Ltd.; Before her employment at USB, she has also received speaker honoraria and travel funding by Novartis. Ludwig Kappos received no personal compensation; his institutions (University Hospital Basel\/Stiftung Neuroimmunology and Neuroscience Basel) received payments for steering committee, advisory and data safety monitoring board participation, consultancy services, and educational activities from Bayer, Biogen, Bristol Myers Squibb, Celltrion Inc, Clene Nanomedicine Inc., EMD Serono Research and development, Galapagos NV, Genentech, Immunic AG, Janssen, Kiniksa Pharmaceuticals, Laboratoires Juvise Pharmaceuticals, Merck Healthcare AG, MSD Merck Sharp & Dohme AG, Minoryx Therapeutics S.L., Neurostatus-UHB AG, Novartis, Roche, Sanofi, Shionogi BV, Wellmera AG, Zai Lab; research support from Novartis, Roche, and Innosuisse. J. Kuhle received speaker fees, research support, travel support, and\/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030_ 189140\/1), University of Basel, Progressive MS Alliance, Bayer, Biogen, Bristol Myers Squibb, Celgene, Merck, Novartis, Octave Bioscience, Roche, and Sanofi. Athina Papadopoulou\u2019s Institutions (USB, University of Basel) received Speaker fees\/advisory boards from: AbbVie, Eli Lilly, Lundbeck, Pfizer, Organon, Sanofi-Genzyme, Teva, research support from: Swiss Multiple Sclerosis Society, Swiss Headache Society, \u201cStiftung zur F\u00f6rderung der gastroenterologischen und allgemeinen klinischen Forschung sowieder medizinischen Bildauswertung\u201d, \u201cFreie Akademische Gesellschaft Basel\u201d, and Swiss National Science Foundation. AP received also travel support from: Abbvie, Bayer AG, Eli Lilly, Hoffmann-La Roche, Teva.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the local ethics committee (Ethikkommission Nordwest- und Zentralschweiz (EKNZ); Project IDs: 285\/11 and 2023\u201302144) and conducted in accordance with the Declaration of Helsinki and its later amendments. All participants gave written informed consent before inclusion in the study.","order":2,"name":"Ethics","label":"Ethical standards","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"517"}}