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.