{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:52:35Z","timestamp":1783367555186,"version":"3.54.6"},"reference-count":44,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American European Congress of Ophthalmic Surgery","award":["AECOS-2019"],"award-info":[{"award-number":["AECOS-2019"]}]},{"name":"Ruhr-University Bochum","award":["AECOS-2019"],"award-info":[{"award-number":["AECOS-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Femtosecond laser-assisted in situ keratomileusis (Femto-LASIK) represents a common treatment modality in refractive surgery and shows excellent results in terms of safety, efficacy, predictability, and long-term stability. However, patients may be affected by dry eye symptoms. The aim of this study was to identify a potential association between subjective dry eye symptoms, objective dry eye markers, and possible changes in the tear film, which could be a target for future therapy development. Therefore, clinical (dry eye) examinations (OSDI, Schirmer test, lissamine green and fluorescein staining, BUT, visual acuity) were carried out before LASIK as well as 5 and 90 days post-OP. The dry eye marker MMP-9, cytokines (IL-1\u03b2, IL-8), and pain markers (NGF, CGRP) were quantified in tear samples with immunoassays. In addition, correlation analyses were performed. Clinical examinations revealed an upregulated OSDI score 5 days post-OP and an increased lissamine green staining score 90 days post-OP. Downregulated CGRP levels were noted 5 days post-OP, while other protein markers were not significantly altered after Femto-LASIK. Hence, Femto-LASIK surgery induced subjective symptoms like that of dry eye which could objectively rather be classified as Femto-LASIK-related discomfort. In the future, this could possibly be better detected and treated using pain markers such as CGRP.<\/jats:p>","DOI":"10.3390\/ijms23147512","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T09:41:10Z","timestamp":1657100470000},"page":"7512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Changes of Subjective Symptoms and Tear Film Biomarkers following Femto-LASIK"],"prefix":"10.3390","volume":"23","author":[{"given":"Teresa","family":"Tsai","sequence":"first","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohannad","family":"Alwees","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Rost","sequence":"additional","affiliation":[{"name":"Center for Refractive Surgery M\u00fcnster, Eye Department, St. Francis-Hospital M\u00fcnster, Hohenzollernring 70, 48145 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Theile","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Burkhard","family":"Dick","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-0829","authenticated-orcid":false,"given":"Stephanie C.","family":"Joachim","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suphi","family":"Taneri","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"},{"name":"Center for Refractive Surgery M\u00fcnster, Eye Department, St. Francis-Hospital M\u00fcnster, Hohenzollernring 70, 48145 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10654-015-0010-0","article-title":"Prevalence of refractive error in Europe: The European Eye Epidemiology (E(3)) Consortium","volume":"30","author":"Williams","year":"2015","journal-title":"Eur. J. Epidemiol."},{"key":"ref_2","first-page":"693","article-title":"Refractive errors","volume":"113","author":"Schiefer","year":"2016","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1001\/jama.2020.20328","article-title":"Complications of Contact Lenses","volume":"325","author":"Kates","year":"2021","journal-title":"JAMA"},{"key":"ref_4","first-page":"401","article-title":"Refractive Surgery: History in the Making","volume":"6","author":"Faith","year":"2017","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1076\/soph.18.1.2.14074","article-title":"LASIK vs LASEK vs PRK: Advantages and indications","volume":"18","author":"Ambrosio","year":"2003","journal-title":"Semin. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"DES109","DOI":"10.1167\/iovs.17-23538","article-title":"Dry Eye After LASIK","volume":"59","author":"Toda","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jcrs.2003.07.003","article-title":"Chronic dry eye and regression after laser in situ keratomileusis for myopia","volume":"30","author":"Albietz","year":"2004","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"(2007). The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. Ocul. Surf., 5, 75\u201392.","DOI":"10.1016\/S1542-0124(12)70081-2"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/00003226-200007000-00016","article-title":"Survey of preferred tests for diagnosis of the tear film and dry eye","volume":"19","author":"Korb","year":"2000","journal-title":"Cornea"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Roda, M., Corazza, I., Bacchi Reggiani, M.L., Pellegrini, M., Taroni, L., Giannaccare, G., and Versura, P. (2020). Dry Eye Disease and Tear Cytokine Levels-A Meta-Analysis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093111"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajo.2017.08.021","article-title":"Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction","volume":"183","author":"Liu","year":"2017","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1167\/iovs.08-2476","article-title":"Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome","volume":"50","author":"Chotikavanich","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1097\/ICO.0000000000000494","article-title":"Correlation Between Tear Film Osmolarity and the Disease Score of the International Chronic Ocular Graft-Versus-Host-Disease Consensus Group in Hematopoietic Stem Cell Transplantation Patients","volume":"34","author":"Schargus","year":"2015","journal-title":"Cornea"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/ICU.0b013e3283543b61","article-title":"Nerve growth factor therapy for corneal disease","volume":"23","author":"Lambiase","year":"2012","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1136\/bjophthalmol-2020-316417","article-title":"Photophobia: Shared pathophysiology underlying dry eye disease, migraine and traumatic brain injury leading to central neuroplasticity of the trigeminothalamic pathway","volume":"105","author":"Diel","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"132417","DOI":"10.1155\/2015\/132417","article-title":"Dry Eye Disease following Refractive Surgery: A 12-Month Follow-Up of SMILE versus FS-LASIK in High Myopia","volume":"2015","author":"Wang","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shen, Z., Zhu, Y., Song, X., Yan, J., and Yao, K. (2016). Dry Eye after Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted in Situ Keratomileusis (FS-LASIK) for Myopia: A Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168081"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.3109\/02713683.2015.1107590","article-title":"Comparison of Corneal Biological Healing After Femtosecond LASIK and Small Incision Lenticule Extraction Procedure","volume":"41","author":"Xia","year":"2016","journal-title":"Curr. Eye Res."},{"key":"ref_19","first-page":"18","article-title":"Change of tear osmolarity after refractive surgery","volume":"74","author":"Kacerovska","year":"2018","journal-title":"Ceska a Slovenska Oftalmologie Casopis Ceske Oftalmologicke Spolecnosti a Slovenske Oftalmologicke Spolecnosti"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/ICL.0b013e3181b3e87f","article-title":"Elevated nerve growth factor in dry eye associated with established contact lens wear","volume":"35","author":"Liu","year":"2009","journal-title":"Eye Contact Lens"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1001\/archopht.118.5.615","article-title":"Reliability and validity of the Ocular Surface Disease Index","volume":"118","author":"Schiffman","year":"2000","journal-title":"Arch. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2147\/OPTH.S164570","article-title":"Evaluation of femtosecond laser in flap and cap creation in corneal refractive surgery for myopia: A 3-year follow-up","volume":"12","author":"Elmohamady","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Barber, L., Khodai, O., Croley, T., Lievens, C., Montaquila, S., Ziemanski, J., McCart, M., Lunacsek, O., Burk, C., and Patel, V. (2018). Dry eye symptoms and impact on vision-related function across International Task Force guidelines severity levels in the United States. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0919-7"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"833984","DOI":"10.3389\/fmed.2022.833984","article-title":"Evaluation of Dry Eye After Refractive Surgery According to Preoperative Meibomian Gland Status","volume":"9","author":"Gong","year":"2022","journal-title":"Front Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.joco.2018.05.002","article-title":"Association between dry eye symptoms and signs","volume":"30","author":"Kyei","year":"2018","journal-title":"J. Curr. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6125","DOI":"10.1167\/iovs.10-5390","article-title":"An objective approach to dry eye disease severity","volume":"51","author":"Sullivan","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1167\/iovs.11-9155","article-title":"Long-term changes in corneal structure and tear inflammatory mediators after orthokeratology and LASIK","volume":"53","author":"Porta","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Eah, K.S., Lee, H., Kim, J.Y., and Tchah, H. (2021). Changes in Tear Osmolarity and Matrix Metalloproteinase-9 Relative to Ocular Discomfort after Femtosecond Laser-Assisted Cataract Surgery. Appl. Sci., 11.","DOI":"10.3390\/app112411878"},{"key":"ref_29","first-page":"243","article-title":"Quantification of a panel for dry-eye protein biomarkers in tears: A comparative pilot study using standard ELISA and customized microarrays","volume":"27","author":"Soria","year":"2021","journal-title":"Mol. Vis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1136\/bjophthalmol-2015-307607","article-title":"Evaluation of point-of-care test for elevated tear matrix metalloproteinase 9 in post-LASIK dry eyes","volume":"100","author":"Chan","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s40135-013-0008-2","article-title":"Dry Eye and Biomarkers: Present and Future","volume":"1","author":"Deschamps","year":"2013","journal-title":"Curr. Ophthalmol. Rep."},{"key":"ref_32","first-page":"993","article-title":"The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment","volume":"10","author":"Resan","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.4103\/1673-5374.213534","article-title":"Neurotrophic factors and corneal nerve regeneration","volume":"12","author":"Sacchetti","year":"2017","journal-title":"Neural Regen Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gao, S., Li, S., Liu, L., Wang, Y., Ding, H., Li, L., and Zhong, X. (2014). Early changes in ocular surface and tear inflammatory mediators after small-incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107370"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ajo.2004.12.051","article-title":"Nerve growth factor concentration and implications in photorefractive keratectomy vs laser in situ keratomileusis","volume":"139","author":"Lee","year":"2005","journal-title":"Am. J. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3928\/1081597X-20210423-01","article-title":"Tear Neuromediator and Corneal Denervation Following SMILE","volume":"37","author":"Chin","year":"2021","journal-title":"J. Refract. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100762","DOI":"10.1016\/j.preteyeres.2019.05.003","article-title":"Corneal nerves in health and disease","volume":"73","author":"Dhillon","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"518","DOI":"10.3928\/1081597X-20160603-01","article-title":"Long-term Effects of LASIK on Corneal Innervation and Tear Neuropeptides and the Associations With Dry Eye","volume":"32","author":"Chao","year":"2016","journal-title":"J. Refract. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1001\/archophthalmol.2011.200","article-title":"Alterations of tear neuromediators in dry eye disease","volume":"129","author":"Lambiase","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.exer.2006.02.004","article-title":"Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye","volume":"83","author":"Corrales","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1038\/s41598-020-60427-2","article-title":"Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration","volume":"10","author":"Guo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tsai, T., Kuehn, S., Tsiampalis, N., Vu, M.K., Kakkassery, V., Stute, G., Dick, H.B., and Joachim, S.C. (2018). Anti-inflammatory cytokine and angiogenic factors levels in vitreous samples of diabetic retinopathy patients. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194603"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/s41598-020-80102-w","article-title":"Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses","volume":"11","author":"Gunawardana","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1167\/iovs.07-1550","article-title":"Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment","volume":"49","author":"Coral","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:43:35Z","timestamp":1760139815000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":44,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23147512"],"URL":"https:\/\/doi.org\/10.3390\/ijms23147512","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]}}}