{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:26:42Z","timestamp":1788964002900,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Neurological disorders significantly affect ocular surface homeostasis, influencing parameters such as blink rate (BR), tear production, corneal nerve density, and sensitivity. This review summarizes recent findings on ocular surface alterations associated with neurological diseases, including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Guillain-Barr\u00e9 syndrome (GBS), trigeminal neuralgia (TN), multiple sclerosis (MS), and Charcot\u2013Marie\u2013Tooth disease (CMT). Notably, ocular manifestations such as reduced BR, decreased tear break-up time (TBUT), impaired tear secretion, and corneal nerve fiber loss are consistently reported. In AD, elevated tear amyloid-beta and tau proteins emerge as promising biomarkers for early disease detection. PD patients frequently experience dry eye symptoms attributed to reduced BR and tear film instability. GBS is linked to lagophthalmos and corneal nerve impairment, potentially leading to severe ocular surface damage. TN demonstrates bilateral ocular surface dysfunction despite unilateral neuropathic symptoms. MS is associated with significant ocular surface alterations, reflecting broader neuroinflammatory and autonomic disturbances. Similarly, CMT patients show reduced corneal sensitivity and tear production, underscoring the systemic nature of neurological impacts. Awareness of these ocular manifestations is essential for improving patient care and guiding future research into ocular biomarkers and targeted therapies.<\/jats:p>","DOI":"10.3390\/medicina61091693","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:24:25Z","timestamp":1758198265000},"page":"1693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ocular Surface Changes Associated with Neurological Diseases"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-8879","authenticated-orcid":false,"given":"Reda","family":"Zemaitiene","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Medical Academy, Lithuanian University of Health Sciences, 44037 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-639X","authenticated-orcid":false,"given":"Gigi","family":"Gorgadze","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tbilisi State Medical University, Tbilisi 0177, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6426-7616","authenticated-orcid":false,"given":"Laura","family":"Mockaitiene","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical Academy, Lithuanian University of Health Sciences, 44037 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II Pathophysiology Report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1111\/opo.12888","article-title":"The Global Prevalence of Dry Eye Disease: A Bayesian View","volume":"41","author":"Papas","year":"2021","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1097\/ICL.0000000000000663","article-title":"Biomarkers in Tears and Ocular Surface: A Window for Neurodegenerative Diseases","volume":"46","author":"Roda","year":"2020","journal-title":"Eye Contact Lens"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jtos.2023.08.001","article-title":"Molecular Nature of Ocular Surface Barrier Function, Diseases That Affect It, and Its Relevance for Ocular Drug Delivery","volume":"30","author":"Kaur","year":"2023","journal-title":"Ocul. Surf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1007\/s00415-022-11014-0","article-title":"Undetected Ophthalmological Disorders in Parkinson\u2019s Disease","volume":"269","author":"Borm","year":"2022","journal-title":"J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/7854_2024_527","article-title":"Cognitive Decline in Alzheimer\u2019s Disease","volume":"69","author":"Testo","year":"2025","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s Disease Facts and Figures. Alzheimers Dement., 19, 1598\u20131695.","DOI":"10.1002\/alz.13016"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","article-title":"Synergy between Amyloid-\u03b2 and Tau in Alzheimer\u2019s Disease","volume":"23","author":"Busche","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.exer.2019.03.012","article-title":"APP Processing and Metabolism in Corneal Fibroblasts and Epithelium as a Potential Biomarker for Alzheimer\u2019s Disease","volume":"182","author":"Choi","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1167\/iovs.18-24694","article-title":"Ocular Biomarkers of Alzheimer\u2019s Disease: The Role of Anterior Eye and Potential Future Directions","volume":"59","author":"Dehghani","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Romaus-Sanjurjo, D., Regueiro, U., L\u00f3pez-L\u00f3pez, M., V\u00e1zquez-V\u00e1zquez, L., Ouro, A., Lema, I., and Sobrino, T. (2022). Alzheimer\u2019s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052486"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s10792-024-03162-1","article-title":"Corneal Innervation Changes in Alzheimer\u2019s: Implications for Sensory Dysfunction","volume":"44","author":"Oltulu","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2147\/EB.S391608","article-title":"Changes in Ocular Biomarkers from Normal Cognitive Aging to Alzheimer\u2019s Disease: A Pilot Study","volume":"15","author":"Chaitanuwong","year":"2023","journal-title":"Eye Brain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.2174\/1567205019666211227102706","article-title":"Blink Rate Study in Patients with Alzheimer\u2019s Disease, Mild Cognitive Impairment and Subjective Cognitive Decline","volume":"18","author":"Bartolo","year":"2021","journal-title":"Curr. Alzheimer Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dehghani, C., Frost, S., Jayasena, R., Fowler, C., Masters, C.L., Kanagasingam, Y., Jiao, H., Lim, J.K.H., Chinnery, H.R., and Downie, L.E. (2020). Morphometric Changes to Corneal Dendritic Cells in Individuals with Mild Cognitive Impairment. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.556137"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s12031-025-02368-x","article-title":"Neuroinflammation Markers in Tear Fluid of Mild Alzheimer\u2019s Disease","volume":"75","author":"Saari","year":"2025","journal-title":"J. Mol. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gharbiya, M., Visioli, G., Trebbastoni, A., Albanese, G.M., Colardo, M., D\u2019Antonio, F., Segatto, M., and Lambiase, A. (2023). Beta-Amyloid Peptide in Tears: An Early Diagnostic Marker of Alzheimer\u2019s Disease Correlated with Choroidal Thickness. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032590"},{"key":"ref_19","first-page":"352","article-title":"Ocular Biomarkers in Alzheimer\u2019s Disease: Insights into Early Detection through Eye-Based Diagnostics\u2014A Literature Review","volume":"175","author":"Firmani","year":"2024","journal-title":"Clin. Ter."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cger.2019.08.002","article-title":"Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology","volume":"36","author":"Simon","year":"2020","journal-title":"Clin. Geriatr. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.amjmed.2019.03.001","article-title":"Parkinson\u2019s Disease and Parkinsonism","volume":"132","author":"Hayes","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1539","DOI":"10.1212\/WNL.0000000000009214","article-title":"Seeing Ophthalmologic Problems in Parkinson Disease: Results of a Visual Impairment Questionnaire","volume":"94","author":"Borm","year":"2020","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7706205060","DOI":"10.5014\/ajot.2023.050235","article-title":"Visual Dysfunction and Occupational Performance in Persons with Parkinson\u2019s Disease","volume":"77","author":"Tester","year":"2023","journal-title":"Am. J. Occup. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ungureanu, L., Chaudhuri, K.R., Diaconu, S., and Falup-Pecurariu, C. (2023). Dry Eye in Parkinson\u2019s Disease: A Narrative Review. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1236366"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41531-021-00225-3","article-title":"Corneal Nerve Fiber Loss Relates to Cognitive Impairment in Patients with Parkinson\u2019s Disease","volume":"7","author":"Che","year":"2021","journal-title":"npj Parkinsons Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nagino, K., Sung, J., Oyama, G., Hayano, M., Hattori, N., Okumura, Y., Fujio, K., Akasaki, Y., Huang, T., and Midorikawa-Inomata, A. (2022). Prevalence and Characteristics of Dry Eye Disease in Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22037-y"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Buzzi, M., Giannaccare, G., Cennamo, M., Bernabei, F., Rothschild, P.R., Vagge, A., Scorcia, V., and Mencucci, R. (2022). Ocular Surface Features in Patients with Parkinson Disease on and Off Treatment: A Narrative Review. Life, 12.","DOI":"10.3390\/life12122141"},{"key":"ref_29","first-page":"S359","article-title":"Dry Eye and Parkinson\u2019s Disease: A Literature Review [abstract]","volume":"35","author":"Yaisawang","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/S0140-6736(21)00517-1","article-title":"Guillain-Barr\u00e9 Syndrome","volume":"397","author":"Shahrizaila","year":"2021","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e16365","DOI":"10.1111\/ene.16365","article-title":"Guillain-Barr\u00e9 Syndrome: A Comprehensive Review","volume":"31","author":"Bellanti","year":"2024","journal-title":"Eur. J. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1136\/jnnp-2020-324230","article-title":"Guillain-Barr\u00e9 Syndrome in Times of Pandemics","volume":"91","author":"Leonhard","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14","DOI":"10.35702\/nrj.10014","article-title":"Blink Reflex Value in the Early Diagnosis of Guillain-Barr\u00e9 Syndrome","volume":"5","author":"Ansary","year":"2023","journal-title":"Neuro Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1097\/WNO.0000000000001885","article-title":"Guillain-Barr\u00e9 Syndrome with Associated Bilateral Neurotrophic Keratopathy","volume":"44","author":"Qin","year":"2024","journal-title":"J. Neuroophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cden.2022.07.008","article-title":"Trigeminal Neuralgia","volume":"67","author":"Khawaja","year":"2023","journal-title":"Dent. Clin. N. Am."},{"key":"ref_36","first-page":"S37","article-title":"Diagnosis and Treatment of Trigeminal Neuralgia: Consensus Statement from the Spanish Society of Neurology\u2019s Headache Study Group","volume":"38","author":"Latorre","year":"2023","journal-title":"Neurologia (Engl. Ed.)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.2147\/JPR.S331036","article-title":"Trigeminal Neuralgia: Current Approaches and Emerging Interventions","volume":"14","author":"Xu","year":"2021","journal-title":"J. Pain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/head.14370","article-title":"Impact of Unilateral Trigeminal Neuralgia on Bilateral Ocular Surface Alterations","volume":"62","author":"Oltulu","year":"2022","journal-title":"Headache"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s10792-022-02521-0","article-title":"Characteristics of the Ocular Surface in Neurotrophic Keratitis Induced by Trigeminal Nerve Injury Following Neurosurgery","volume":"43","author":"Xie","year":"2023","journal-title":"Int. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple Sclerosis\u2014A Review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e37297","DOI":"10.1097\/MD.0000000000037297","article-title":"Review of Multiple Sclerosis: Epidemiology, Etiology, Pathophysiology, and Treatment","volume":"103","author":"Haki","year":"2024","journal-title":"Medicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s10792-021-02031-5","article-title":"Conjunctival Impression Cytology and Tear Film Parameters in Patients with Multiple Sclerosis","volume":"42","author":"Oltulu","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.34172\/jrcm.32220","article-title":"Frequency of Dry Eye Syndrome in Patients with Multiple Sclerosis: A Cross-Sectional Case Control Study","volume":"12","author":"Sorkhabi","year":"2024","journal-title":"J. Res. Clin. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000443706","article-title":"Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review","volume":"46","author":"Barreto","year":"2016","journal-title":"Neuroepidemiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.2169\/internalmedicine.7463-21","article-title":"MFN2-Related Charcot-Marie-Tooth Disease with Atypical Ocular Manifestations","volume":"60","author":"Nan","year":"2021","journal-title":"Intern. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1007\/s40123-022-00524-9","article-title":"Charcot\u2013Marie\u2013Tooth disease and implications on corneal refractive surgery","volume":"11","author":"Moshirfar","year":"2022","journal-title":"Ophthalmol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e941094","DOI":"10.12659\/AJCR.941094","article-title":"Severe dry eye disease in Charcot\u2013Marie\u2013Tooth disease: A comprehensive case report","volume":"24","author":"Aldihan","year":"2023","journal-title":"Am. J. Case Rep."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/9\/1693\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:44Z","timestamp":1760035664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/9\/1693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["medicina61091693"],"URL":"https:\/\/doi.org\/10.3390\/medicina61091693","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]}}}