Corneal Nerve Morphology, Sensitivity, and Tear Neuropeptides in Contact Lens Wear

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To determine tear neuropeptide levels in contact lens wearers and non-wearers, and to examine relationships with indices of corneal innervation, tear function, and ocular discomfort.


A cross-sectional, single-visit, investigator-masked pilot study. Assessments included Ocular Comfort Index (OCI), central and mid-peripheral corneal nerve density and morphology (HRT-Rostock), corneal sensitivity (Cochet-Bonnet aesthesiometer), tear Substance P and calcitonin gene-related peptide (CGRP) concentration (ELISA), in situ tear osmolarity (TearLab), tear secretion (Phenol Red Thread), and noninvasive tear break-up time (NITBUT; Keeler Tearscope). Groups were compared using independent t-test or Mann–Whitney U test, and regional differences assessed using paired t-tests. Associations were analyzed using Pearson or Spearman correlation. Significance was determined at P < .05.


Twenty contact lens wearers (7M:13F, 32 ± 5 years) and 20 non-wearers (7M:13F, 31 ± 5 years) completed the study. OCI score was numerically higher in lens wearers (32.27 ± 5.33) than non-wearers (27.66 ± 9.94). Tear osmolarity was higher [298.0 (IQR 291.0–309.8) vs. 288.5 (282.3–298.3) mOsmol/L; P = .01] whereas NITBUT was lower (9.8 ± 3.4 vs. 13.8 ± 5.6 s; P = .01) in lens wearers compared with non-wearers. Tear neuropeptide concentrations were not different between groups [Substance P 4.29 ng/ml (IQR 1.57–6.05), CGRP 14.89 ng/ml (5.08–59.26)], and there were no differences in nerve morphology or ocular surface sensitivity. Higher nerve density, interconnections, and tortuosity were observed in the central cornea than mid-peripherally (P < .05). OCI score was moderately associated with nerve tortuosity (r = 0.42, P = .01). CGRP was associated with central nerve density (ρ = 0.38, P = .02), as was tear secretion (r = −0.37, P = .02). Nerve interconnections were strongly associated with corneal sensitivity (ρ = 0.64, P < .001).


Relationships were demonstrated between nerve density, tear CGRP, and corneal sensitivity. Markers of corneal neurobiology and sensory function do not appear to be altered in contact lens wear despite worse tear function (osmolarity and stability) in lens wearers. This suggests that mechanisms other than overt changes in corneal innervation regulate tear function during lens wear. The relationship between nerve tortuosity and ocular discomfort requires elucidation.

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