Evidence map›Paper›PMID 28736339›Full record

ReviewThe ocular surface2017

TFOS DEWS II pain and sensation report.

Carlos Belmonte, Jason J Nichols, Stephanie M Cox, James A Brock, Carolyn G Begley, David A Bereiter, Darlene A Dartt, Anat Galor, Pedram Hamrah, Jason J Ivanusic and 5 more

Registry-linked trialOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The ocular surface, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06841471 (Association Between Corneal Sensitivity, Nerve Morphology, Tear Film Homeostasis and Dry Eye Symptoms), which is not on this map. Cited by 327 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
327citing papers in PubMed, 5 pooled it
46.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06841471 recruitingnot on this mapstarted 2025, after this paper: background citation

Association Between Corneal Sensitivity, Nerve Morphology, Tear Film Homeostasis and Dry Eye Symptoms

Typeobservational_patient_registrySponsorDaniela NoschRan2025 to 2025Enrolled140ConditionsDry Eye Disease (DED), Dry Eye, Dry Eye Sensation, Corneal Nerve
3 · Its place in the literature

Who cites it

327 citing papers in PubMed, 5 syntheses or guidelines pooled it, 619 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. A randomized crossover trial: The impact of ocular lubrication on migraine severity in persons with dry eye disease and migraine.Optometry and vision science : official publication of the American Academy of Optometry · 2025
    Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Article
  14. Article
  15. Article
  16. Article
  17. Analytical Performance, Spatial Dynamics and Clinically Meaningful Change Thresholds for Automated Non-invasive Tear Film Assessment Using the Oculus Keratograph 5M.Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) · 2026
    Article
  18. Review
  19. Article
  20. Review

267 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 13 institutions in 4 countries.

Carlos BelmonteInstituto de Neurociencias de Alicante, University Miguel Hernandez-CSIC, Instituto Fernandez-Vega, Oviedo University, Spain. Electronic address: carlos.belmonte@umh.es.
Jason J NicholsSchool of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA.
Stephanie M CoxSchool of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA.
James A BrockDepartment of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, 3010, Australia.
Carolyn G BegleySchool of Optometry, Indiana University, Bloomington, IN, USA.
David A BereiterSchool of Dentistry, University of Minnesota, Minneapolis, MN, USA.
Darlene A DarttSchepens Eye Research Institute, Massachusetts Eye and Ear, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Harvard University, Boston, MA, USA.
Anat GalorSurgical Services, Miami Veterans Administration Medical Center, Miami, FL, USA; Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, FL, USA.
Pedram HamrahCornea Service, New England Eye Center/Tufts Medical Center, Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA; Center for Translational Ocular Immunology, Tufts Medical Center, Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
Jason J IvanusicDepartment of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, 3010, Australia.
Deborah S JacobsBostonSight, Needham and Harvard Medical School, MA, USA.
Nancy A McNamaraSchool of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
Mark I RosenblattDepartment of Ophthalmology and Vision Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL, USA.
Fiona StapletonSchool of Optometry and Vision Science, University of New South Wales, Sydney, Australia.
James S WolffsohnOphthalmic Research Group, Aston University, Birmingham, UK.
University of Alabama at Birmingham · USUniversity of Melbourne · AUAston University · GBHarvard University · USIndiana University Bloomington · USInstituto de Neurociencias · ESMassachusetts Eye and Ear Infirmary · USTufts University · USUniversity of California, Berkeley · USUniversity of Illinois Chicago · USUniversity of Miami · USUniversity of Minnesota · USUNSW Sydney · AU

Funding

Conjunctival Goblet Cell Mucin Secretion in Inflammation and Its ResolutionR01EY019470 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI DARTT, DARLENE A · 2009 to 2023
$7.4M
NEI NIH HHS R01 EY019470
6 · The paper itself

Abstract

Pain associated with mechanical, chemical, and thermal heat stimulation of the ocular surface is mediated by trigeminal ganglion neurons, while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of meibomian gland secretion or mucin release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy.

Indexed as

PainAnimalsCorneaDry Eye SyndromesNociceptorsSensationThermoreceptorsCentral nervous systemCold receptorsCorneal esthesiometryDry eye diseaseIn vivo confocal microscopyMechano-nociceptorsNeuropathic painOcular surface drynessPainPeripheral sensory nervesPolymodal nociceptorsSensationTrigeminal brainstem nuclear complexTRP channels

Identifiers

PMID28736339
PMCPMC5706540
OpenAlexW2737725878

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.