Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye

Graefes Arch Clin Exp Ophthalmol. 2015 Nov;253(11):2029-39. doi: 10.1007/s00417-015-3120-1. Epub 2015 Aug 11.


Purpose: The most likely etiology of post-LASIK dry eye is corneal nerve damage; however, no direct relationship between post-LASIK dry eye symptoms and nerve damage has been established, and limited information is available about the relationship between dry eye signs and corneal reinnervation after LASIK. Tear neuropeptides (SP and CGRP) are important in the maintenance of corneal nerve health, but the impact of LASIK has not yet been studied. This study evaluated changes in nerve morphology, tear neuropeptide, and dry eye, so as to establish the relationship between reinnervation and dry eye and to assess the role of tear neuropeptides in reinnervation post-LASIK.

Methods: Twenty non-dry eye volunteers who had undergone bilateral myopic-LASIK completed this study. Corneal nerve morphology (density, width, interconnections, and tortuosity), SP and CGRP concentration, and dry eye were monitored over time prior to, 1 day, 1 week, 1, 3, and 6 months post-LASIK.

Results: Dry eye symptoms and tear function, except for osmolarity (P = 0.003), remained unchanged post-LASIK. Corneal nerve morphology decreased immediately, and did not return to preoperative levels by 6 months post-LASIK (P < 0.001). Increased tear SP concentration was observed 3 months post-LASIK (P < 0.001). Associations between reinnervation as measured by increased density and lower tear SP (P = 0.03), and between increased density and decreased dry eye symptoms (P = 0.01) were found post-LASIK.

Conclusion: An inverse relationship between reinnervation post-LASIK and dry eye symptoms was found, confirming that post-LASIK dry eye is a neuropathic disease. This study is the first to demonstrate an association between tear SP and post-LASIK reinnervation, suggesting that strategies for manipulating neuropeptide concentration to improve reinnervation may improve ocular comfort post-LASIK.

Keywords: Corneal nerve morphology; Corneal reinnervation; Corneal sensitivity; Dry eye; LASIK; Tear neuropeptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Calcitonin Gene-Related Peptide / metabolism
  • Cornea / innervation*
  • Dry Eye Syndromes / etiology
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / physiopathology*
  • Eye Proteins / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Keratomileusis, Laser In Situ / methods*
  • Lasers, Excimer / therapeutic use*
  • Male
  • Myopia / metabolism
  • Myopia / physiopathology
  • Myopia / surgery*
  • Ophthalmic Nerve / physiopathology*
  • Postoperative Complications*
  • Prospective Studies
  • Substance P / metabolism
  • Tears / metabolism
  • Young Adult


  • Eye Proteins
  • tear proteins
  • Substance P
  • Calcitonin Gene-Related Peptide