{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T22:23:29Z","timestamp":1781130209139,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Multiple sclerosis (MS) is a common neurological disease affecting the optic nerve, directly or indirectly, through transsynaptic axonal degeneration along the visual pathway. New ophthalmological tools, arguably the most important being optical coherence tomography (OCT), could prove paramount in redefining MS diagnoses and shaping their follow-up protocols, even when the optic nerve is not involved. Methods: A prospective clinical study was conducted. In total, 158 eyes from patients previously diagnosed with relapsing remitting MS (RRMS)\u2014with or without optic neuritis (ON), clinically isolated syndrome (CIS) with or without ON, and healthy controls were included. Each patient underwent an ophthalmologic exam and OCT evaluation for both eyes (a posterior pole analysis (PPA) and the optic nerve head radial circle protocol (ONH-RC)). Results: The macular retinal thickness (the 4 \u00d7 4, respectively, 2 \u00d7 2 grid) and thickness of the peripapillary retinal nerve fiber layer (pRNFL) were investigated. Various layers of the retina were also compared. Our study observed significant pRNFL thinning in the RRMS eyes compared to the control group, the pRNFL atrophy being more severe in the RRMS-ON eyes than the RRMS-NON eyes. In the ON group, the macular analysis showed statistically significant changes in the RRMS-ON eyes when compared only to the CIS-ON eyes, regarding decreases in the inner plexiform layer (IPL) thickness and inner nuclear layer (INL) on the central 2 \u00d7 2 macular grid. The neurodegenerative process affected both the inner retina and pRNFL, with clinical damage appearing for the latter in the following order: CIS-NON, CIS-ON, RRMS-NON, and RRMS-ON. In the presence of optic neuritis, SMRR patients presented an increase in their outer retina thickness compared to CIS patients. Conclusions: To differentiate the MS patients from the CIS patients, in the absence of optic neuritis, OCT Posterior Pole Analysis could be a useful tool when using a central 2 \u00d7 2 sectors macular grid. Retinal changes in MS seem to start from the fovea and spread to the posterior pole. Finally, MS could lead to alterations in both the inner and outer retina, along with pRNFL.<\/jats:p>","DOI":"10.3390\/diagnostics13122077","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"2077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identifying Optical Coherence Tomography Markers for Multiple Sclerosis Diagnosis and Management"],"prefix":"10.3390","volume":"13","author":[{"given":"Larisa","family":"Cujba","sequence":"first","affiliation":[{"name":"Medical Doctoral School, University of Oradea, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Stan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-0512","authenticated-orcid":false,"given":"Ovidiu","family":"Samoila","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-262X","authenticated-orcid":false,"given":"Tudor","family":"Drugan","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-0473","authenticated-orcid":false,"given":"Ancuta","family":"Benedec (Cutas)","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3222-6448","authenticated-orcid":false,"given":"Cristina","family":"Nicula","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","unstructured":"Williams, A.L. (2019). Multiple Sclerosis Sourcebook: Basic Consumer Health Information about Multiple Sclerosis (MS) and Its Effects on Mobility, Vision, Bladder Function, Speech, Swallowing, and Cognition, Including Facts about Risk Factors, Causes, Diagnostic Procedures, Pain Management, Drug Treatments, and Physical and Occupational Therapies, Omnigraphics."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1474-4422(18)30443-5","article-title":"Global, regional, and national burden of multiple sclerosis 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Wallin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3389\/fncel.2019.00063","article-title":"Glial Contribution to Excitatory and Inhibitory Synapse Loss in Neurodegeneration","volume":"13","author":"Henstridge","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1212\/WNL.26.6_Part_2.26","article-title":"Distribution of plaques in seventy autopsy cases of multiple sclerosis in the United States","volume":"26","author":"Ikuta","year":"1976","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"134858","DOI":"10.1155\/2013\/134858","article-title":"The Afferent Visual Pathway: Designing a Structural-Functional Paradigm of Multiple Sclerosis","volume":"2013","author":"Costello","year":"2013","journal-title":"ISRN Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.5152\/npa.2015.12608","article-title":"Clinically Isolated Syndromes: Clinical Characteristics, Differential Diagnosis, and Management","volume":"52","author":"Efendi","year":"2016","journal-title":"Noro Psikiyatr. Arsivi"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cordon, B., Vilades, E., Orduna, E., Satue, M., Perez-Velilla, J., Sebastian, B., Polo, V., Larrosa, J.M., Pablo, L.E., and Garcia-Martin, E. (2020). Angiography with optical coherence tomography as a biomarker in multiple sclerosis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243236"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/brain\/awaa361","article-title":"Retinal asymmetry in multiple sclerosis","volume":"144","author":"Petzold","year":"2020","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.msard.2012.12.004","article-title":"Measures of visual pathway structure and function in MS: Clinical usefulness and role for MS trials","volume":"2","author":"Galetta","year":"2013","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.msard.2016.12.005","article-title":"Sensitivity of visual evoked potentials and spectral domain optical coherence tomography in early relapsing remitting multiple sclerosis","volume":"12","author":"Behbehani","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1055\/s-0036-1579692","article-title":"Vision Disturbances in Multiple Sclerosis","volume":"36","author":"Costello","year":"2016","journal-title":"Semin. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.3390\/cimb44090272","article-title":"Optic Neuritis in Multiple Sclerosis\u2014A Review of Molecular Mechanisms Involved in the Degenerative Process","volume":"44","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1097\/WCO.0000000000000604","article-title":"Optical coherence tomography as a means to characterize visual pathway involvement in multiple sclerosis","volume":"31","author":"Wicki","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S1474-4422(17)30278-8","article-title":"Retinal layer segmentation in multiple sclerosis: A systematic review and meta-analysis","volume":"16","author":"Petzold","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_16","unstructured":"(User Manual Software, 2016). User Manual Software, Version 6.5, Spectralis Glaucoma Module Premium Edition."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1016\/j.ophtha.2014.06.047","article-title":"Relationship between ganglion cell layer thickness and estimated retinal ganglion cell counts in the glaucomatous macula","volume":"121","author":"Zhang","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/cne.903000103","article-title":"Topography of ganglion cells in human retina","volume":"300","author":"Curcio","year":"1990","journal-title":"J. Comp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1093\/brain\/awq146","article-title":"A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials","volume":"133","author":"Henderson","year":"2010","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1167\/iovs.09-4577","article-title":"Interrelationship of optical coherence tomography and multifocal visual-evoked potentials after optic neuritis","volume":"51","author":"Klistorner","year":"2010","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2302","DOI":"10.1002\/brb3.2302","article-title":"Optical coherence tomography monitoring and diagnosing retinal changes in multiple sclerosis","volume":"11","author":"Mehmood","year":"2021","journal-title":"Brain Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/S1474-4422(12)70213-2","article-title":"Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: A retrospective study","volume":"11","author":"Saidha","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rzepi\u0144ski, \u0141., Kucharczuk, J., Maciejek, Z., Grzybowski, A., and Parisi, V. (2021). Spectral-Domain Optical Coherence Tomography Assessment in Treatment-Na\u00efve Patients with Clinically Isolated Syndrome and Different Multiple Sclerosis Types: Findings and Relationship with the Disability Status. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132892"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1177\/1352458512439237","article-title":"Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography","volume":"18","author":"Albrecht","year":"2012","journal-title":"Mult. Scler. J."},{"key":"ref_25","first-page":"521","article-title":"Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis","volume":"135","author":"Saidha","year":"2011","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/ana.22005","article-title":"Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis","volume":"67","author":"Talman","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.ophtha.2011.11.032","article-title":"Ganglion cell loss in relation to visual disability in multiple sclerosis","volume":"119","author":"Walter","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Martucci, A., Landi, D., Cesareo, M., Di Carlo, E., Di Mauro, G., Sorge, R.P., Albanese, M., Nicoletti, C.G., Mataluni, G., and Mercuri, N.B. (2021). Complex Rearrangement of the Entire Retinal Posterior Pole in Patients with Relapsing Remitting Multiple Sclerosis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10204693"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"858","DOI":"10.3389\/fneur.2020.00858","article-title":"Morphological Outer Retina Findings in Multiple Sclerosis Patients with or without Optic Neuritis","volume":"11","author":"Ziccardi","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Schneider, E., Zimmermann, H., Oberwahrenbrock, T., Kaufhold, F., Kadas, E.M., Petzold, A., Bilger, F., Borisow, N., Jarius, S., and Wildemann, B. (2013). Optical coherence tomography reveals distinct patterns of retinal damage in neuromyelitis optica and multiple sclerosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066151"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1177\/1352458513518626","article-title":"Disease course heterogeneity and OCT in multiple sclerosis","volume":"20","author":"Balk","year":"2014","journal-title":"Mult. Scler. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/brain\/awq346","article-title":"Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography","volume":"134","author":"Saidha","year":"2011","journal-title":"Brain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2147\/EB.S229814","article-title":"Retinal Nerve Fiber Layer Thickness and Total Macular Volume in Multiple Sclerosis Subtypes and Their Relationship with Severity of Disease, a Cross-Sectional Study","volume":"12","author":"Eslami","year":"2020","journal-title":"Eye Brain"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/ana.25738","article-title":"Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy","volume":"87","author":"Sotirchos","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1093\/brain\/awq080","article-title":"Ocular pathology in multiple sclerosis: Retinal atrophy and inflammation irrespective of disease duration","volume":"133","author":"Green","year":"2010","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kaushik, M., Wang, C.Y., Barnett, M.H., Garrick, R., Parratt, J., Graham, S.L., Sriram, P., Yiannikas, C., and Klistorner, A. (2013). Inner nuclear layer thickening is inversley proportional to retinal ganglion cell loss in optic neuritis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078341"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/12\/2077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:55:40Z","timestamp":1760126140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/12\/2077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["diagnostics13122077"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13122077","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]}}}