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Volume 14
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10.3390/jcm14134406
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery

by
Cristina Valencia-Sandonís
1,
Amanda Vázquez
1,2,
Laura Valencia-Nieto
1,
Elena Martínez-Plaza
1,
Marta Blanco-Vázquez
1,
Eva M. Sobas
1,
Margarita Calonge
1,3,
Enrique Ortega
1,2,
Amalia Enríquez-de-Salamanca
1,3,† and
María J. González-García
1,3,*,†
1
Institute of Applied Ophthalmobiology (IOBA), Universidad de Valladolid (UVa), Campus Miguel Delibes, Paseo de Belén 17, 47011 Valladolid, Spain
2
Pain Unit, Alliance of University Hospitals, Health System of Castilla y León, Calle Dulzaina 2, 47012 Valladolid, Spain
3
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Miguel Delibes, Paseo de Belén 17, 47011 Valladolid, Spain
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2025, 14(13), 4406; https://doi.org/10.3390/jcm14134406
Submission received: 10 April 2025 / Revised: 19 May 2025 / Accepted: 19 June 2025 / Published: 20 June 2025
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment: 2nd Edition)
Versions Notes

Abstract

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 ± 8.43 years) were included, with a mean time between visits of 4.83 ± 1.10 years. DE symptoms, measured with the Ocular Surface Disease Index questionnaire, improved at V2 (p < 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 < 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 < 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.
Keywords: neuropathic ocular pain; dry eye; refractive surgery; tear biomarkers neuropathic ocular pain; dry eye; refractive surgery; tear biomarkers

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MDPI and ACS Style

Valencia-Sandonís, C.; Vázquez, A.; Valencia-Nieto, L.; Martínez-Plaza, E.; Blanco-Vázquez, M.; Sobas, E.M.; Calonge, M.; Ortega, E.; Enríquez-de-Salamanca, A.; González-García, M.J. Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery. J. Clin. Med. 2025, 14, 4406. https://doi.org/10.3390/jcm14134406

AMA Style

Valencia-Sandonís C, Vázquez A, Valencia-Nieto L, Martínez-Plaza E, Blanco-Vázquez M, Sobas EM, Calonge M, Ortega E, Enríquez-de-Salamanca A, González-García MJ. Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery. Journal of Clinical Medicine. 2025; 14(13):4406. https://doi.org/10.3390/jcm14134406

Chicago/Turabian Style

Valencia-Sandonís, Cristina, Amanda Vázquez, Laura Valencia-Nieto, Elena Martínez-Plaza, Marta Blanco-Vázquez, Eva M. Sobas, Margarita Calonge, Enrique Ortega, Amalia Enríquez-de-Salamanca, and María J. González-García. 2025. "Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery" Journal of Clinical Medicine 14, no. 13: 4406. https://doi.org/10.3390/jcm14134406

APA Style

Valencia-Sandonís, C., Vázquez, A., Valencia-Nieto, L., Martínez-Plaza, E., Blanco-Vázquez, M., Sobas, E. M., Calonge, M., Ortega, E., Enríquez-de-Salamanca, A., & González-García, M. J. (2025). Long-Term Evolution of Chronic Neuropathic Ocular Pain and Dry Eye Following Corneal Refractive Surgery. Journal of Clinical Medicine, 14(13), 4406. https://doi.org/10.3390/jcm14134406

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