{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:04:27Z","timestamp":1784880267622,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stearacl Inc., Toronto, Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 (\u22121, 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080910","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute Tear Secretion Response to Menthol Delivered as a Vapor to the Eye: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-7816","authenticated-orcid":false,"given":"Reinhold","family":"Vieth","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 5th Floor, King\u2019s College Circle, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Medical Sciences Building, 5th Floor, King\u2019s College Circle, Toronto, ON M5S 1A8, Canada"},{"name":"Stearacl Inc., Toronto, ON M4K 1X4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Independent Researcher, Toronto, ON M4K 1X3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Rapson","sequence":"additional","affiliation":[{"name":"Rapson Pain & Acupuncture Clinic, Toronto, ON M4X 1W4, Canada"},{"name":"Department of Family and Community Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1089\/jop.2017.0050","article-title":"Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye Versus Normal Subjects","volume":"33","author":"Corcoran","year":"2017","journal-title":"J. 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