June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye vs Normal Subjects
Author Affiliations & Notes
  • Peter Corcoran
    R&D, Ora, Inc, Andover, Massachusetts, United States
  • Michael Watson
    Dry Eye, Ora, Inc, Andover, Massachusetts, United States
  • George W Ousler
    Dry Eye, Ora, Inc, Andover, Massachusetts, United States
  • Endri Angjeli
    R&D, Ora, Inc, Andover, Massachusetts, United States
  • Keith Jeffrey Lane
    R&D, Ora, Inc, Andover, Massachusetts, United States
  • Mark B Abelson
    Ora, Inc, Andover, Massachusetts, United States
  • David A Hollander
    Ora, Inc, Andover, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Peter Corcoran, Ora, Inc (E); Michael Watson, Ora, Inc (E); George Ousler, Ora, Inc (E); Endri Angjeli, Ora, Inc (E); Keith Lane, Ora, Inc (E); Mark Abelson, Ora, Inc (E), Ora, Inc (P); David Hollander, Ora, Inc (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 469. doi:
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    • Get Citation

      Peter Corcoran, Michael Watson, George W Ousler, Endri Angjeli, Keith Jeffrey Lane, Mark B Abelson, David A Hollander; Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye vs Normal Subjects. Invest. Ophthalmol. Vis. Sci. 2017;58(8):469.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To assess the sensitivity of corneal cold receptors to a known TRPM8 agonist, menthol, in dry eye and normals and determine whether factors, such as disease duration or age, affect responses.

Methods : Dry Eye (DED; N=33) and normal (N=15) subjects were randomly assigned to receive Rohto® Hydra (0.01% menthol) or Systane® Ultra treatments (OU) in a prospective, double-blind, cross-over study. DED subjects had documented disease and symptom response scores >2 on a 0 to 5-point scale. Normals had no history of DED and scores <2 on the same scale. Endpoints included mean cooling score (MCS: 0=not cool; 10=very cool, 10=highest possible score) evaluated at 0-minutes (m), 0.5m, 1m, 2m, 3m, 4m post-instillation; sum cooling scores (SCS: 5 time points summed, 60=highest possible score), and ocular signs (staining, TFBUT, Schirmer’s test) and symptoms. Corneal sensitivity was assessed with Cochet-Bonnet esthesiometry. Subgroups of </>10 years DED-duration were assessed

Results : MCS at 0.5-4m post-menthol instillation were significantly higher in DED (p≤0.03). Corneal sensitivity scores based on Cochet bonnet mechanical sensitivity) were not different between groups. The duration of dry eye disease based on < 10-yr (N=18, 28.3 ± 2.58) versus >10 years (N=15, 20.2 ± 2.76) was directly correlated with MCS, while no statistically significant differences were found in MCS based on age. Similar tear production (Schirmer’s score), corneal staining, TFBUT, and symptoms were also observed in the two patient populations with different duration of DED.

Conclusions : DED subjects had greater sensitivity to the TRPM8 agonist, menthol, than normal subjects. DED duration, and not age, was critical to cooling sensitivity. The finding that cooling scores were higher in subjects with DED for fewer than 10-years compared to more than 10-years suggests that corneal cold receptor sensitivity decreases as the duration of DED increases. These findings reveal new possibilities for future study of the role TRPM8-mediated sensory dysfunction plays in ineffective compensatory mechanisms in dry eye, and how targeting these aspects of pathophysiology might benefit patients.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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