Acute Tear Secretion Response to Menthol Delivered as a Vapor to the Eye: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial.

Menthol is an agonist of TRPM8 receptors that activates tear secretion.

Objectives

The hypothesis was that menthol delivered to the cornea in vapor form could stimulate tear secretion without irritation.

Methods

This was a randomized, placebo-controlled, double-blind clinical trial of menthol vapor. Thirty generally healthy participants were randomized to the treatment or placebo group.

Results

Median age was 58 (43, 73 IQR) years, 18 participants (60%) were female; 12 (40%) were male. Tear weight exceeded 5 mg in 2 (13.3%) of the placebo group, versus 13 (86.7%) of the menthol group (p = 0.020). Median weight of tears wiped from below the eye in the placebo group was 3 (-1, 8 IQR) mg versus 13 (8, 35 IQR) mg in the menthol group (p = 0.002). Nasolacrimal drainage in the placebo group weighed 10 (4,12 IQR) mg versus 56 (22, 173 IQR) mg in the menthol group (p < 0.001). The treated right eye felt qualitatively moister than the untreated left eye in 7 (47%) of the placebo group, versus 15 (100%) of the menthol group (p = 0.002). No participant reported eye irritation or any adverse effects at the one-week follow-up.

Conclusions

Menthol delivered to the eye as vapor evoked tear secretion without eye irritation. Menthol vapor warrants further study as a complementary treatment or an alternative to eye drops for dry eye disease.