{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:27:45Z","timestamp":1792697265536,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Parkinson disease (PD) is a progressive, neurodegenerative disease of the central nervous system. Visual disturbance is one of the most frequent nonmotor abnormalities referred to by patients suffering from PD at early stages. Furthermore, ocular surface alterations including mainly dry eye and blink reduction represent another common finding in patients with PD. Tears of PD patients show specific alterations related to protein composition, and in vivo confocal microscopy has demonstrated profound changes in different corneal layers in this setting. These changes can be attributed not only to the disease itself, but also to the medications used for its management. In particular, signs of corneal toxicity, both at epithelial and endothelial level, are well described in the literature in PD patients receiving amantadine. Management of PD patients from the ophthalmologist\u2019s side requires knowledge of the common, but often underdiagnosed, ocular surface alterations as well as of the signs of drug toxicity. Furthermore, ocular surface biomarkers can be useful for the early diagnosis of PD as well as for monitoring the degree of neural degeneration over time.<\/jats:p>","DOI":"10.3390\/life12122141","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T06:24:44Z","timestamp":1671431084000},"page":"2141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ocular Surface Features in Patients with Parkinson Disease on and off Treatment: A Narrative Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Matilde","family":"Buzzi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-0289","authenticated-orcid":false,"given":"Giuseppe","family":"Giannaccare","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Magna Gr\u00e6cia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Cennamo","sequence":"additional","affiliation":[{"name":"Eye Clinic, Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Bernabei","sequence":"additional","affiliation":[{"name":"Service d\u2019Ophtalmologie, Ophtalmop\u00f4le de Paris, H\u00f4pital Cochin, AP-HP, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Raphael","family":"Rothschild","sequence":"additional","affiliation":[{"name":"Service d\u2019Ophtalmologie, Ophtalmop\u00f4le de Paris, H\u00f4pital Cochin, AP-HP, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-9267","authenticated-orcid":false,"given":"Aldo","family":"Vagge","sequence":"additional","affiliation":[{"name":"Eye Clinic of Genoa, Policlinico San Martino, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-7957","authenticated-orcid":false,"given":"Vincenzo","family":"Scorcia","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Magna Gr\u00e6cia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-6363","authenticated-orcid":false,"given":"Rita","family":"Mencucci","sequence":"additional","affiliation":[{"name":"Eye Clinic, Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.12659\/MSM.890861","article-title":"Ophthalmological Features of Parkinson Disease","volume":"20","author":"Nowacka","year":"2014","journal-title":"Med. Sci. Monit."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1007\/s00415-018-9051-0","article-title":"Early Ophthalmologic Features of Parkinson\u2019s Disease: A Review of Preceding Clinical and Diagnostic Markers","volume":"266","author":"Turcano","year":"2019","journal-title":"J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1212\/01.WNL.0000103444.45882.D8","article-title":"Ophthalmologic Features of Parkinson\u2019s Disease","volume":"62","author":"Biousse","year":"2004","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1468-1331.2005.01025.x","article-title":"Ocular Complications of Neurological Therapy","volume":"12","author":"Hadjikoutis","year":"2005","journal-title":"Eur. J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3109\/02713683.2014.930154","article-title":"Corneal Sensitivity and Tear Function in Neurodegenerative Diseases","volume":"40","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_6","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 Sci. Clin. Pr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/mds.20213","article-title":"Movement Disorder Society Task Force Report on the Hoehn and Yahr Staging Scale: Status and Recommendations","volume":"19","author":"Goetz","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement Disorder Society-Sponsored Revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18348","DOI":"10.1038\/s41598-022-22037-y","article-title":"Prevalence and Characteristics of Dry Eye Disease in Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"12","author":"Nagino","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s10072-016-2574-1","article-title":"Evaluation of Corneal Parameters in Patients with Parkinson\u2019s Disease","volume":"37","author":"Demirci","year":"2016","journal-title":"Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1795.e1","DOI":"10.1016\/j.ophtha.2005.04.025","article-title":"Tear Film Tests in Parkinson\u2019s Disease Patients","volume":"112","author":"Tamer","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00002826-199402000-00010","article-title":"Lacrimation in Parkinson\u2019s Disease","volume":"17","author":"Bagheri","year":"1994","journal-title":"Clin. Neuropharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S1542-0124(11)70034-9","article-title":"Non-Hormonal Systemic Medications and Dry Eye","volume":"9","author":"Wong","year":"2011","journal-title":"Ocul. Surf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/eye.1991.65","article-title":"Meibomian Gland Disease. Classification and Grading of Lid Changes","volume":"5","author":"Bron","year":"1991","journal-title":"Eye"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3346\/jkms.1994.9.3.239","article-title":"Schrimer Test in Parkinson\u2019s Disease","volume":"9","author":"Kwon","year":"1994","journal-title":"J. Korean Med. Sci."},{"key":"ref_16","first-page":"20","article-title":"Meibum Lipid Composition and Conformation in Parkinsonism","volume":"12","author":"Blinchevsky","year":"2021","journal-title":"EC Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1080\/00207454.2020.1761353","article-title":"Evaluation of Corneal Sublayers Thickness and Corneal Parameters in Patients with Parkinson\u2019s Disease","volume":"131","author":"Ulusoy","year":"2021","journal-title":"Int. J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jcjo.2013.12.010","article-title":"Central Corneal Thickness and Its Relationship to Parkinson\u2019s Disease Severity","volume":"49","author":"Aksoy","year":"2014","journal-title":"Can. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3389\/fneur.2017.00329","article-title":"Eyelid Dysfunction in Neurodegenerative, Neurogenetic, and Neurometabolic Disease","volume":"8","author":"Hamedani","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s00415-011-6261-0","article-title":"Case-Control Study of Blink Rate in Parkinson\u2019s Disease under Different Conditions","volume":"259","author":"Fitzpatrick","year":"2012","journal-title":"J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/ana.410120614","article-title":"Blink Rates in Parkinsonism","volume":"12","author":"Karson","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/mds.21887","article-title":"Voluntary, Spontaneous, and Reflex Blinking in Parkinson\u2019s Disease","volume":"23","author":"Agostino","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.parkreldis.2015.10.019","article-title":"Small Fiber Neuropathy in Parkinson\u2019s Disease: A Clinical, Pathological and Corneal Confocal Microscopy Study","volume":"21","author":"Javed","year":"2015","journal-title":"Park. Relat Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20147","DOI":"10.1038\/s41598-020-76768-x","article-title":"Corneal Confocal Microscopy Detects Small Fibre Neurodegeneration in Parkinson\u2019s Disease Using Automated Analysis","volume":"10","author":"Lim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_25","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 Park. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41531-020-00148-5","article-title":"Parkinson\u2019s Disease with Restless Legs Syndrome\u2014An in Vivo Corneal Confocal Microscopy Study","volume":"7","author":"Lagali","year":"2021","journal-title":"npj Park. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jocn.2017.02.033","article-title":"Corneal Nerve Microstructure in Parkinson\u2019s Disease","volume":"39","author":"Misra","year":"2017","journal-title":"J. Clin. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/ICO.0b013e3182574ade","article-title":"Corneal Sensitivity, Blink Rate, and Corneal Nerve Density in Progressive Supranuclear Palsy and Parkinson Disease","volume":"32","author":"Reddy","year":"2013","journal-title":"Cornea"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/ICO.0000000000001517","article-title":"Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study","volume":"37","author":"Arrigo","year":"2018","journal-title":"Cornea"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.parkreldis.2016.04.033","article-title":"Evidence for Small Fiber Neuropathy in Early Parkinson\u2019s Disease","volume":"28","author":"Podgorny","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1002\/mds.28602","article-title":"Corneal Confocal Microscopy Identifies Parkinson\u2019s Disease with More Rapid Motor Progression","volume":"36","author":"Lim","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_32","first-page":"498","article-title":"Measurement of Corneal Nerve Fiber Parameters in Patients with Parkinson\u2019s Disease","volume":"101","author":"Che","year":"2021","journal-title":"Natl. Med. J. China"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/ICO.0000000000001951","article-title":"Corneal Evaluation in Patients With Parkinsonism on Long-Term Amantadine Therapy","volume":"38","author":"Daggumilli","year":"2019","journal-title":"Cornea"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.parkreldis.2019.03.001","article-title":"Proteomic Analysis of Tear Fluid Reveals Disease-Specific Patterns in Patients with Parkinson\u2019s Disease\u2014A Pilot Study","volume":"63","author":"Boerger","year":"2019","journal-title":"Park. Relat. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neulet.2013.08.019","article-title":"Tear Levels of Tumor Necrosis Factor-Alpha in Patients with Parkinson\u2019s Disease","volume":"553","author":"Acar","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.2217\/bmm-2019-0315","article-title":"Levels of Oligomeric \u03b1-Synuclein in Reflex Tears Distinguish Parkinson\u2019s Disease Patients from Healthy Controls","volume":"13","author":"Janga","year":"2019","journal-title":"Biomark. Med."},{"key":"ref_37","first-page":"941","article-title":"Oligomeric \u03b1-Synuclein Is Increased in Basal Tears of Parkinson\u2019s Patients","volume":"13","author":"Okamoto","year":"2018","journal-title":"Biomark. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Acera, A., G\u00f3mez-Esteban, J.C., Murueta-Goyena, A., Galdos, M., Azkargorta, M., Elortza, F., Ruzafa, N., Ibarrondo, O., Pereiro, X., and Vecino, E. (2022). Potential Tear Biomarkers for the Diagnosis of Parkinson\u2019s Disease\u2014A Pilot Study. Proteomes, 10.","DOI":"10.3390\/proteomes10010004"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bogdanov, V., Kim, A., Nodel, M., Pavlenko, T., Pavlova, E., Blokhin, V., Chesnokova, N., and Ugrumov, M. (2021). A Pilot Study of Changes in the Level of Catecholamines and the Activity of \u03b1-2-Macroglobulin in the Tear Fluid of Patients with Parkinson\u2019s Disease and Parkinsonian Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094736"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.32607\/20758251-2019-11-4-99-103","article-title":"Tear Fluid Catecholamines as Biomarkers of the Parkinson\u2019s Disease: A Clinical and Experimental Study","volume":"11","author":"Kim","year":"2019","journal-title":"Acta Nat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1007\/s12035-018-1315-2","article-title":"Upgraded Methodology for the Development of Early Diagnosis of Parkinson\u2019s Disease Based on Searching Blood Markers in Patients and Experimental Models","volume":"56","author":"Kim","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/S0002-9394(14)76952-1","article-title":"Amantadine and Corneal Deposits","volume":"110","author":"Fraunfelder","year":"1990","journal-title":"Am. J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1001\/jama.237.12.1200a","article-title":"Vision Loss Associated with Amantadine Hydrochloride Use","volume":"237","author":"Pearlman","year":"1977","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/00003226-199004000-00017","article-title":"Amantadine Caused Corneal Edema","volume":"9","author":"Blanchard","year":"1990","journal-title":"Cornea"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1007\/BF00839973","article-title":"Superficial Punctate Keratitis and Corneal Abrasion Due to Amantadine Hydrochloride","volume":"240","author":"Nogaki","year":"1993","journal-title":"J. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100852","DOI":"10.1016\/j.ajoc.2020.100852","article-title":"Amantadine Can Induce Intra-Epithelial Deposition in the Cornea","volume":"19","author":"Yoshinaka","year":"2020","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.parkreldis.2010.02.013","article-title":"Amantadine-Associated Corneal Edema","volume":"16","author":"Ghaffariyeh","year":"2010","journal-title":"Park. Relat. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.2147\/OPTH.S166384","article-title":"Clinical and Genetic Investigation of Amantadine-Associated Corneal Edema","volume":"12","author":"Hessen","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10384-010-0888-8","article-title":"Sudden Onset of Amantadine-Induced Reversible Bilateral Corneal Edema in an Elderly Patient: Case Report and Literature Review","volume":"55","author":"Hotehama","year":"2011","journal-title":"Jpn J. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1097\/01.ico.0000130417.91438.7e","article-title":"Reversible Amantadine-Induced Corneal Edema in an Adolescent","volume":"23","author":"Hughes","year":"2004","journal-title":"Cornea"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.ophtha.2008.03.011","article-title":"Amantadine-Associated Corneal Edema. Potentially Irreversible Even after Cessation of the Medication","volume":"115","author":"Jeng","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1755-3768.2009.01561.x","article-title":"Sudden Bilateral Corneal Oedema in a Patient with Parkinson\u2019s Disease","volume":"89","author":"Park","year":"2011","journal-title":"Acta Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1097\/ICO.0b013e3181450d4c","article-title":"Postmarketing Surveillance of Corneal Edema, Fuchs Dystrophy, and Amantadine Use in the Veterans Health Administration","volume":"26","author":"French","year":"2007","journal-title":"Cornea"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.ophtha.2009.10.039","article-title":"The Effect of Amantadine on Corneal Endothelium in Subjects with Parkinson\u2019s Disease","volume":"117","author":"Chang","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.exer.2019.02.010","article-title":"Effects of Amantadine on Corneal Endothelium","volume":"181","author":"Dudley","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ajo.2016.08.034","article-title":"Amantadine Use as a Risk Factor for Corneal Edema: A Nationwide Cohort Study in Taiwan","volume":"171","author":"Lee","year":"2016","journal-title":"Am. J. Ophthalmol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/12\/2141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:44:03Z","timestamp":1760147043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/12\/2141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,19]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["life12122141"],"URL":"https:\/\/doi.org\/10.3390\/life12122141","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,19]]}}}