{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T21:30:13Z","timestamp":1784842213851,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T00:00:00Z","timestamp":1742601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS), characterized by inflammation, demyelination, and neurodegeneration, resulting in the disruption of axonal signal conduction. Optic neuritis (ON) occurs in over 70% of MS cases, highlighting the involvement of the optic nerve in the progression of the disease. Optic nerve atrophy secondary to the inflammatory episode can be observed during fundoscopy as pallor in the temporal quadrant or of the entire optic disc. Our study aims to evaluate the diagnostic capacity of fundus ophthalmoscopy when compared with the temporal thickness of the pRNFL (peripapillary retinal nerve fiber layer) measured using optical coherence tomography (OCT). Methods: We analyzed 88 eyes from 44 relapsing remitting MS patients using fundus photography (FP) and OCT optic disc measurements, correlating the temporal pallor of the optic disc seen in fundus photographs (FPs) with structural parameters obtained using OCT. Results: Our analysis revealed the significant capacity of optic disc pallor grading using FPs in MS patients in order to discriminate between normal and quadrants with pallor (p = 0.006) or strong pallor (p = 0.003) and between ones with light pallor and moderate pallor (p = 0.002) or strong pallor (p = 0.001), while being unable to clearly differentiate between normal quadrants and ones with light pallor (p = 0.608) or between pallor and strong pallor (p = 0.33). Conclusions: Fundoscopy and FP are useful screening tools in evaluating optic nerve atrophy in MS patients that could be used to assess neurodegeneration because of their universal availability. With the proposed inclusion of the optic disc as the fifth part of the CNS, the optic nerve will benefit from multiple exploratory techniques in order to increase the understanding of disease progression and patient quality of life.<\/jats:p>","DOI":"10.3390\/jcm14072166","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T06:21:38Z","timestamp":1742797298000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluating Fundoscopy as a Screening Tool for Optic Nerve Atrophy in Multiple Sclerosis: An Optical Coherence Tomography (OCT) Comparative Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-3932","authenticated-orcid":false,"given":"Vlad Constantin","family":"Donica","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-2921","authenticated-orcid":false,"given":"Ciprian","family":"Danielescu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisia Iuliana","family":"Alexa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1116-1585","authenticated-orcid":false,"given":"Irina Andreea","family":"Pavel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Lori","family":"Donica","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Grosu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u0103lina Anda","family":"Sandu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-7714","authenticated-orcid":false,"given":"Camelia Margareta","family":"Bogd\u0103nici","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105435","DOI":"10.1016\/j.msard.2024.105435","article-title":"Consensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines","volume":"83","author":"Yamout","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1212\/CON.0000000000000768","article-title":"Optic Neuritis","volume":"25","author":"Bennett","year":"2019","journal-title":"CONTINUUM Lifelong Learn. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Puthenparampil, M., Federle, L., Poggiali, D., Miante, S., Signori, A., Pilotto, E., Rinaldi, F., Perini, P., Sormani, M.P., and Midena, E. (2017). Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183957"},{"key":"ref_4","first-page":"330","article-title":"Optic Nerve Head Changes in Patients with Optic Neuritis Secondary to Multiple Sclerosis: A Comparison of The Affected and Fellow Healthy Eyes","volume":"35","author":"Emir","year":"2020","journal-title":"Medeni. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2147\/EB.S54131","article-title":"Optic neuritis as an early sign of multiple sclerosis","volume":"8","author":"Kale","year":"2016","journal-title":"Eye Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e200805","DOI":"10.1212\/WNL.0000000000207805","article-title":"Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria: A Longitudinal, Prospective, Multicenter Study","volume":"102","author":"Rovira","year":"2024","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e784","DOI":"10.1212\/WNL.0000000000207507","article-title":"Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for Multiple Sclerosis","volume":"101","author":"Bsteh","year":"2023","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Donica, V.C., Alexa, A.I., Pavel, I.A., Danielescu, C., Ciap\u0103, M.A., Donica, A.L., and Bogd\u0103nici, C.M. (2023). The Evolvement of OCT and OCT-A in Identifying Multiple Sclerosis Biomarkers. Biomedicines, 11.","DOI":"10.3390\/biomedicines11113031"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/s41433-017-0010-2","article-title":"Optical coherence tomography in multiple sclerosis","volume":"32","author":"Britze","year":"2018","journal-title":"Eye"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1177\/1352458510397414","article-title":"Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients","volume":"17","author":"Pueyo","year":"2011","journal-title":"Mult. Scler. J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cujb\u0103, L., Banc, A., Drugan, T., Coad\u0103, C.A., Cristea, A.-P., Stan, C., and Nicula, C. (2024). Homonymous Hemiatrophy of Macular Ganglion Cell Layer as a Marker of Retrograde Neurodegeneration in Multiple Sclerosis\u2014A Narrative Review. Diagnostics, 14.","DOI":"10.3390\/diagnostics14121255"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1167\/iovs.11-9339","article-title":"Scanning Laser Polarimetry Reveals Status of RNFL Integrity in Eyes with Optic Nerve Head Swelling by OCT","volume":"53","author":"Kupersmith","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1177\/1352458513485149","article-title":"Predictive value of 1 month retinal nerve fiber layer thinning for deficits at 6 months after acute optic neuritis","volume":"19","author":"Kupersmith","year":"2013","journal-title":"Mult. Scler. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/1352458515598020","article-title":"Retinal ganglion cell layer thinning within one month of presentation for optic neuritis","volume":"22","author":"Kupersmith","year":"2015","journal-title":"Mult. Scler. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1089\/tmj.2015.0068","article-title":"Fundus Photography in the 21st Century\u2014A Review of Recent Technological Advances and Their Implications for Worldwide Healthcare","volume":"22","author":"Panwar","year":"2016","journal-title":"Telemed. e-Health"},{"key":"ref_17","first-page":"381","article-title":"Validation of the color graduation scale in the optical nerve photograph, an alternative for qualitative classification","volume":"97","year":"2022","journal-title":"Arch. Soc. Esp. Oftalmol. Engl. Ed."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Midena, E., Marchione, G., Di Giorgio, S., Rotondi, G., Longhin, E., Frizziero, L., Pilotto, E., Parrozzani, R., and Midena, G. (2022). Ultra-wide-field fundus photography compared to ophthalmoscopy in diagnosing and classifying major retinal diseases. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-23170-4"},{"key":"ref_19","first-page":"459","article-title":"Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application","volume":"31","author":"Bambo","year":"2014","journal-title":"Semin. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ahn, S.J., and Kim, Y.H. (2024). Clinical Applications and Future Directions of Smartphone Fundus Imaging. Diagnostics, 14.","DOI":"10.3390\/diagnostics14131395"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40942-021-00313-9","article-title":"Smartphone fundus photography: A narrative review","volume":"7","author":"Iqbal","year":"2021","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1167\/tvst.8.3.29","article-title":"Smartphone-Based, Rapid, Wide-Field Fundus Photography for Diagnosis of Pediatric Retinal Diseases","volume":"8","author":"Patel","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wintergerst, M.W.M., Brinkmann, C.K., Holz, F.G., and Finger, R.P. (2018). Undilated versus dilated monoscopic smartphone-based fundus photography for optic nerve head evaluation. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28585-6"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gelfand, J.M., Goodin, D.S., Boscardin, W.J., Nolan, R., Cuneo, A., and Green, A.J. (2012). Retinal Axonal Loss Begins Early in the Course of Multiple Sclerosis and Is Similar between Progressive Phenotypes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036847"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Muntean, G.A., Marginean, A., Groza, A., Damian, I., Roman, S.A., Hapca, M.C., Muntean, M.V., and Nicoar\u0103, S.D. (2023). The Predictive Capabilities of Artificial Intelligence-Based OCT Analysis for Age-Related Macular Degeneration Progression\u2014A Systematic Review. Diagnostics, 13.","DOI":"10.3390\/diagnostics13142464"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Danielescu, C., Dabija, M.G., Nedelcu, A.H., Lupu, V.V., Lupu, A., Ioniuc, I., G\u00eelc\u0103-Blanariu, G.-E., Donica, V.-C., Anton, M.-L., and Musat, O. (2023). Automated Retinal Vessel Analysis Based on Fundus Photographs as a Predictor for Non-Ophthalmic Diseases\u2014Evolution and Perspectives. J. Pers. Med., 14.","DOI":"10.3390\/jpm14010045"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/tvst.13.7.13","article-title":"SLO-Net: Enhancing Multiple Sclerosis Diagnosis Beyond Optical Coherence Tomography Using Infrared Reflectance Scanning Laser Ophthalmoscopy Images","volume":"13","author":"Arian","year":"2024","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105743","DOI":"10.1016\/j.msard.2024.105743","article-title":"Discrimination of multiple sclerosis using scanning laser ophthalmoscopy images with autoencoder-based feature extraction","volume":"88","author":"Aghababaei","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajo.2019.01.011","article-title":"A Deep Learning Algorithm to Quantify Neuroretinal Rim Loss from Optic Disc Photographs","volume":"201","author":"Thompson","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ajo.2020.03.035","article-title":"Efficacy for Differentiating Nonglaucomatous Versus Glaucomatous Optic Neuropathy Using Deep Learning Systems","volume":"216","author":"Yang","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12974-023-02763-4","article-title":"Optical coherence tomography angiography measurements in multiple sclerosis: A systematic review and meta-analysis","volume":"20","author":"Mohammadi","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/nyas.15060","article-title":"Combining retinal structural and vascular measurements improves discriminative power for multiple sclerosis patients","volume":"1529","author":"Bostan","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pearson, T., Chen, Y., Dhillon, B., Chandran, S., van Hemert, J., and MacGillivray, T. (2022). Multi-modal retinal scanning to measure retinal thickness and peripheral blood vessels in multiple sclerosis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24312-4"},{"key":"ref_34","first-page":"2","article-title":"Quantification of Leukocyte Trafficking in a Mouse Model of Multiple Sclerosis through In Vivo Imaging","volume":"13","author":"Xia","year":"2022","journal-title":"EC Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Buscho, S.E., Xia, F., Shi, S., Lin, J.L., Szczesny, B., Zhang, W., Motamedi, M., and Liu, H. (2023). Non-Invasive Evaluation of Retinal Vascular Alterations in a Mouse Model of Optic Neuritis Using Laser Speckle Flowgraphy and Optical Coherence Tomography Angiography. Cells, 12.","DOI":"10.3390\/cells12232685"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2468","DOI":"10.1212\/WNL.0000000000009504","article-title":"Asymptomatic optic nerve lesions: An underestimated cause of silent retinal atrophy in MS","volume":"94","author":"Davion","year":"2020","journal-title":"Neurology"},{"key":"ref_37","first-page":"808","article-title":"Paediatric optic neuritis: Factors leading to unfavourable outcome and relapses","volume":"102","author":"Mizzi","year":"2017","journal-title":"Br. J. Ophthalmol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/7\/2166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:58:19Z","timestamp":1760029099000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/7\/2166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,22]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["jcm14072166"],"URL":"https:\/\/doi.org\/10.3390\/jcm14072166","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,22]]}}}