Alterations of tear neuromediators in dry eye disease

Arch Ophthalmol. 2011 Aug;129(8):981-6. doi: 10.1001/archophthalmol.2011.200.


Objectives: To evaluate tear levels of neuromediators in patients with dry eye disease and to identify statistical correlations with the clinical findings.

Methods: Nineteen patients with dry eye disease (Sjögren syndrome, n = 5 patients; non-Sjögren syndrome, n = 10; and ocular cicatricial pemphigoid, n = 4) and 12 healthy volunteers were enrolled. The eyes of all participants were evaluated by slitlamp examination, Schirmer testing, fluorescein staining, and tear film break-up time. Grading of dry eye severity was recorded. Tear samples were collected, and substance P, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nerve growth factor (NGF) concentrations were evaluated by enzyme-linked immunoassay and correlated with the clinical findings.

Results: Nerve growth factor tear levels were significantly increased in participants with dry eye disease; CGRP and NPY concentrations were significantly decreased when compared with those in healthy participants. Dry eye severity showed a direct correlation with NGF and an inverse correlation with CGRP and NPY tear levels. Nerve growth factor tear levels showed a direct correlation with conjunctival hyperemia and fluorescein staining results, CGRP directly correlated with Schirmer test values, and NPY inversely correlated with tear film break-up time. Subgroup analysis showed that CGRP and NPY but not NGF were changed in autoimmune (ie, Sjögren syndrome and ocular cicatricial pemphigoid) dry eye disease.

Conclusions: The decreased tear levels of NPY and CGRP in dry eye disease are related to impaired lacrimal function, and tear levels of NGF are more closely related to corneal epithelial damage. Our findings suggest that NPY, CGRP, and NGF could become useful markers of dry eye severity.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Dry Eye Syndromes / classification
  • Dry Eye Syndromes / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Eye Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Growth Factor / metabolism
  • Neuropeptide Y / metabolism
  • Neuropeptides / metabolism*
  • Severity of Illness Index
  • Substance P / metabolism
  • Tears / metabolism*
  • Vasoactive Intestinal Peptide / metabolism


  • Biomarkers
  • Eye Proteins
  • Neuropeptide Y
  • Neuropeptides
  • tear proteins
  • Substance P
  • Vasoactive Intestinal Peptide
  • Nerve Growth Factor
  • Calcitonin Gene-Related Peptide