The Relationship between Corneal Nerve Morphology and Inflammatory Mediators and Neuropeptides in Healthy Individuals

SIGNIFICANCE This study set out to explore the relationship between the ocular surface immune and nervous systems by exploring corneal nerve structure and the presence of inflammatory mediators and neuropeptides in the tear film. PURPOSE The purpose of this study was to determine the association between corneal nerve morphology and tear film inflammatory mediators and a neuropeptide in healthy individuals. METHODS Flush tears were collected from both eyes of 21 healthy participants aged 39.7 ± 9.9 years (10 females, 11 males) and analyzed for substance P, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), tumor necrosis factor α, and interleukin 6. In vivo central corneal confocal microscopy was performed on the right eye, and eight images were captured. Variables measured were corneal nerve fiber length (CNFL), corneal nerve density (CNFD), corneal nerve branch density, fiber total branch density, corneal nerve fiber area, corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrac). For each eye, the average across the images and the maximum and minimum values were determined for each variable. Pearson correlation analysis was performed to test for associations. RESULTS Substance P correlated with CNFrac (max) ( r = −0.48, P = .03) and CNFW (min) ( r = −0.52, P = .02). TIMP-1 correlated with CNFD (average) ( r = −0.53, P = .03), CNFL (average) ( r = −0.49, P = .05), CNFrac (max) ( r = −0.49, P = .05), and CNFD (min) ( r = −0.55, P = .02). Interleukin 6 correlated with CNFW (average) ( r = −0.49, P = .05), the standard deviation of CNFL ( r = −0.51, P = .04), CNFL (max) ( r = −0.50, P = .04), CNFrac (max) ( r = −0.50, P = .04), and CNFW (min) ( r = −0.55, P = .02). Tumor necrosis factor α, matrix metalloproteinase-9, and its ratio with TIMP-1 did not correlate with any corneal nerve parameters. CONCLUSIONS Both inflammatory mediators and neuropeptides correlated with measures of corneal nerve morphology, supporting the link between the inflammatory and nervous systems.