{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:07:17Z","timestamp":1784401637167,"version":"3.55.0"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"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\/Objectives: To compare changes in the thickness of retinal layers between patients with amyotrophic lateral sclerosis (ALS) and healthy controls using optical coherence tomography. Amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motoneurons with a rapidly progressive course, but non-motor symptoms such as decreased ocular motility and reduced visual acuity have also been reported. Specific biomarkers or surrogate parameters assessing neurodegeneration in ALS are of interest. Methods: In a retrospective, longitudinal study using optic coherence tomography of the retinal layers, we compared changes in the thickness of the layers between patients with ALS and healthy controls. Correlations to clinical scores, such as the modified ranking scale, were analyzed. Results: In our cohort of patients with early ALS (disease duration 5.15 \u00b1 21.4 months at baseline), we neither observed differences in retinal layer thickness at baseline nor did the thickness changes in any retinal layer differ in comparison to healthy controls at baseline. Moreover, we observed no significant thickness changes over the course of the observational period in our patients with ALS. However, a correlation analysis revealed a negative association of the thickness change rates in the complex of ganglion cell and inner plexiform layer and the inner nuclear layer with a higher modified Rankin scale at follow-up. Conclusions: This study adds to the notion that OCT may not be a suitable tool to monitor atrophy and disease progression in ALS. However, further longitudinal studies with longer follow-up times and larger cohorts are warranted.<\/jats:p>","DOI":"10.3390\/jcm15010258","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:33:25Z","timestamp":1767191605000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evolution of Retinal Morphology Changes in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Valeria","family":"Koska","sequence":"first","affiliation":[{"name":"Department of Neurology, Maria-Hilf-Clinics, 41063 M\u00f6nchengladbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Teufel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive and Palliative Care, St\u00e4dtisches Klinikum Solingen, 42653 Solingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-034X","authenticated-orcid":false,"given":"Aykut","family":"Aytulun","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, LVR-Klinikum, Heinrich-Heine-University D\u00fcsseldorf, 40204 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Weise","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Ringelstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University D\u00fcsseldorf, 40629 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6038-5577","authenticated-orcid":false,"given":"Rainer","family":"Guthoff","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical Faculty, University Clinic of Heinrich Heine University D\u00fcsseldorf, 40204 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-3501","authenticated-orcid":false,"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7987-658X","authenticated-orcid":false,"given":"Philipp","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Neurology, Maria-Hilf-Clinics, 41063 M\u00f6nchengladbach, Germany"},{"name":"Department of Neurology, Medical Faculty, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S1474-4422(21)00465-8","article-title":"Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic Lateral Sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1136\/jnnp-2011-300141","article-title":"Onset and spreading patterns of lower motor neuron involvements predict survival in sporadic amyotrophic lateral sclerosis","volume":"82","author":"Kimura","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jns.2011.10.016","article-title":"Cross-sectional evaluation of clinical neuro-ophthalmic abnormalities in an amyotrophic lateral sclerosis population","volume":"314","author":"Moss","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JND-210632","article-title":"Non-Motor Symptoms of Amyotrophic Lateral Sclerosis: A Multi-Faceted Disorder","volume":"8","author":"Nash","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1136\/practneurol-2021-003256","article-title":"Diagnosing ALS: The Gold Coast criteria and the role of EMG","volume":"22","author":"Turner","year":"2022","journal-title":"Pract. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/003693305700200504","article-title":"Cerebral vascular accidents in patients over the age of 60: II. Prognosis","volume":"2","author":"Rankin","year":"1957","journal-title":"Scott. Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1161\/01.STR.30.8.1538","article-title":"Use of the Barthel index and modified Rankin scale in acute stroke trials","volume":"30","author":"Sulter","year":"1999","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","article-title":"The ALSFRS-R: A revised ALS functional rating scale that incorporates assessments of respiratory function","volume":"169","author":"Cedarbaum","year":"1999","journal-title":"J. Neurol. Sci."},{"key":"ref_10","unstructured":"The Writing Group (2017). Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: A randomised, double-blind, placebo-controlled trial. Lancet Neurol., 16, 505\u2013512."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3109\/21678421.2014.959024","article-title":"Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients","volume":"15","author":"Abe","year":"2014","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/acn3.765","article-title":"High-frequency motor rehabilitation in amyotrophic lateral sclerosis: A randomized clinical trial","volume":"6","author":"Zucchi","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1007\/s00415-015-7731-6","article-title":"Predicting prognosis in amyotrophic lateral sclerosis: A simple algorithm","volume":"262","author":"Elamin","year":"2015","journal-title":"J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1136\/jnnp-2020-322909","article-title":"Prognostic value of weight loss in patients with amyotrophic lateral sclerosis: A population-based study","volume":"91","author":"Tan","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_15","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 A J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.clineuro.2011.02.014","article-title":"Retinal thickness in patients with mild cognitive impairment and Alzheimer\u2019s disease","volume":"113","author":"Kesler","year":"2011","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Albrecht, P., M\u00fcller, A.-K., S\u00fcdmeyer, M., Ferrea, S., Ringelstein, M., Cohn, E., Aktas, O., Dietlein, T., Lappas, A., and Foerster, A. (2012). Optical coherence tomography in parkinsonian syndromes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034891"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/acn3.46","article-title":"Subtle retinal pathology in amyotrophic lateral sclerosis","volume":"1","author":"Ringelstein","year":"2014","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1212\/WNL.0000000000012125","article-title":"APOSTEL 2.0 Recommendations for Reporting Quantitative Optical Coherence Tomography Studies","volume":"97","author":"Aytulun","year":"2021","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1212\/WNL.0000000000002774","article-title":"The APOSTEL recommendations for reporting quantitative optical coherence tomography studies","volume":"86","author":"Balk","year":"2016","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tewarie, P., Balk, L., Costello, F., Green, A., Martin, R., Schippling, S., and Petzold, A. (2012). The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034823"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1111\/ene.12146","article-title":"Optical coherence tomography does not support optic nerve involvement in amyotrophic lateral sclerosis","volume":"20","author":"Roth","year":"2013","journal-title":"Eur. J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rojas, P., de Hoz, R., Ram\u00edrez, A.I., Ferreras, A., Salobrar-Garcia, E., Mu\u00f1oz-Blanco, J.L., Urcelay-Segura, J.L., Salazar, J.J., and Ram\u00edrez, J.M. (2019). Changes in Retinal OCT and Their Correlations with Neurological Disability in Early ALS Patients, a Follow-Up Study. Brain Sci., 9.","DOI":"10.3390\/brainsci9120337"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1007\/s00415-018-8863-2","article-title":"Reduced retinal nerve fiber layer (RNFL) thickness in ALS patients: A window to disease progression","volume":"265","author":"Rohani","year":"2018","journal-title":"J. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2741","DOI":"10.1002\/brb3.2741","article-title":"Amyotrophic lateral sclerosis and retinal changes in optical coherence tomography: A systematic review and meta-analysis","volume":"12","author":"Nepal","year":"2022","journal-title":"Brain Behav."},{"key":"ref_26","first-page":"T12","article-title":"Ophthalmic Manifestations of Amyotrophic Lateral Sclerosis (An American Ophthalmological Society Thesis)","volume":"113","author":"Volpe","year":"2015","journal-title":"Trans. Am. Ophthalmol. Soc."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/1\/258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:51:49Z","timestamp":1767192709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/1\/258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jcm15010258"],"URL":"https:\/\/doi.org\/10.3390\/jcm15010258","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]}}}