{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:51:00Z","timestamp":1787028660251,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008431","name":"Junta de Castilla y Le\u00f3n and the European Social Fund","doi-asserted-by":"publisher","award":["EDU\/1192\/2020"],"award-info":[{"award-number":["EDU\/1192\/2020"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Junta de Castilla y Le\u00f3n and the European Social Fund","doi-asserted-by":"publisher","award":["SAF-2016-77080-P MICIU\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["SAF-2016-77080-P MICIU\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Junta de Castilla y Le\u00f3n and the European Social Fund","doi-asserted-by":"publisher","award":["FPU15\/01443"],"award-info":[{"award-number":["FPU15\/01443"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Junta de Castilla y Le\u00f3n and the European Social Fund","doi-asserted-by":"publisher","award":["2020"],"award-info":[{"award-number":["2020"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministry of Science, Innovation and Universities (Government of Spain)","doi-asserted-by":"publisher","award":["EDU\/1192\/2020"],"award-info":[{"award-number":["EDU\/1192\/2020"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministry of Science, Innovation and Universities (Government of Spain)","doi-asserted-by":"publisher","award":["SAF-2016-77080-P MICIU\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["SAF-2016-77080-P MICIU\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministry of Science, Innovation and Universities (Government of Spain)","doi-asserted-by":"publisher","award":["FPU15\/01443"],"award-info":[{"award-number":["FPU15\/01443"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministry of Science, Innovation and Universities (Government of Spain)","doi-asserted-by":"publisher","award":["2020"],"award-info":[{"award-number":["2020"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Valladolid","award":["EDU\/1192\/2020"],"award-info":[{"award-number":["EDU\/1192\/2020"]}]},{"name":"University of Valladolid","award":["SAF-2016-77080-P MICIU\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["SAF-2016-77080-P MICIU\/AEI\/10.13039\/501100011033"]}]},{"name":"University of Valladolid","award":["FPU15\/01443"],"award-info":[{"award-number":["FPU15\/01443"]}]},{"name":"University of Valladolid","award":["2020"],"award-info":[{"award-number":["2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Chronic neuropathic ocular pain (NOP) can manifest concurrently with dry eye (DE) symptoms following ocular surgical procedures. Due to its low prevalence, NOP remains an underrecognized and underdiagnosed postoperative complication, leading to suboptimal management. This study evaluated the long-term evolution of symptoms, signs, and tear biomarkers in patients with NOP and DE after corneal refractive surgery (RS). Methods: Patients with chronic NOP and persistent DE-related symptoms after corneal RS were assessed in two visits (V1 and V2), at least two years apart. Symptoms (DE, pain, anxiety, and depression) were measured with specific questionnaires. Clinical examination included a slit-lamp ocular surface evaluation, corneal sensitivity measurement, and subbasal corneal nerve plexus evaluation. Basal tear samples were collected, and a 20-plex cytokine panel and Substance P (SP) were assayed. Results: Twenty-three patients (35.57 \u00b1 8.43 years) were included, with a mean time between visits of 4.83 \u00b1 1.10 years. DE symptoms, measured with the Ocular Surface Disease Index questionnaire, improved at V2 (p &lt; 0.001), along with a reduction in anxiety and depression levels, measured with the Hospital Anxiety and Depression Scale (p = 0.027). Corneal staining also decreased (p &lt; 0.001), while subbasal nerve plexus parameters and corneal sensitivity remained unchanged. Tear analysis revealed increased concentrations of fractalkine\/CX3CL1 (p = 0.039), interleukin (IL)-1 receptor antagonist (Ra) (p = 0.025), IL-10 (p = 0.002), and SP (p &lt; 0.001). Conclusions: Symptom improvement may result from better control of underlying pathologies or natural disease progression. However, the increased levels of SP and fractalkine\/CX3CL1 suggest sustained neurogenic inflammation, while elevated IL-1Ra and IL-10 indicate a potential compensatory anti-inflammatory response.<\/jats:p>","DOI":"10.3390\/jcm14134406","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:13:56Z","timestamp":1750407236000},"page":"4406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-039X","authenticated-orcid":false,"given":"Cristina","family":"Valencia-Sandon\u00eds","sequence":"first","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-0083","authenticated-orcid":false,"given":"Amanda","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Pain Unit, Alliance of University Hospitals, Health System of Castilla y Le\u00f3n, Calle Dulzaina 2, 47012 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-991X","authenticated-orcid":false,"given":"Laura","family":"Valencia-Nieto","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-2478","authenticated-orcid":false,"given":"Elena","family":"Mart\u00ednez-Plaza","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Blanco-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-8616","authenticated-orcid":false,"given":"Eva M.","family":"Sobas","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8178-4836","authenticated-orcid":false,"given":"Margarita","family":"Calonge","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Ortega","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Pain Unit, Alliance of University Hospitals, Health System of Castilla y Le\u00f3n, Calle Dulzaina 2, 47012 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1274-7796","authenticated-orcid":false,"given":"Amalia","family":"Enr\u00edquez-de-Salamanca","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3673-0585","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Miguel Delibes, Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40662-015-0019-1","article-title":"The European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO): A Database Study of Trends in Volumes, Surgical Techniques and Outcomes of Refractive Surgery","volume":"2","author":"Manning","year":"2015","journal-title":"Eye Vis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.4103\/IJO.IJO_3406_22","article-title":"Refractive Surgery and Dry Eye\u2014An Update","volume":"71","author":"Nair","year":"2023","journal-title":"Indian J. 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