title: Tear osmolarity in the diagnosis and management of dry eye disease.
abstract: OBJECTIVE
  To evaluate the use of tear osmolarity in the diagnosis of dry eye disease.
  
  
  METHODS
  A prospective, observational case series to determine the clinical usefulness of tear osmolarity and commonly used objective tests to diagnose dry eye disease.
  
  
  METHODS
  A multicenter, 10-site study consisting of 314 consecutive subjects between 18 and 82 years of age. Bilateral tear osmolarity, tear film break-up time (TBUT), corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading were performed. Diagnostic performance was measured against a composite index of objective measurements that classified subjects as having normal, mild or moderate, or severe dry eye. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic curve, and intereye variability.
  
  
  RESULTS
  Of the 6 tests, tear osmolarity was found to have superior diagnostic performance. The most sensitive threshold between normal and mild or moderate subjects was found to be 308 mOsms/L, whereas the most specific was found at 315 mOsms/L. At a cutoff of 312 mOsms/L, tear hyperosmolarity exhibited 73% sensitivity and 92% specificity. By contrast, the other common tests exhibited either poor sensitivity (corneal staining, 54%; conjunctival staining, 60%; meibomian gland grading, 61%) or poor specificity (tear film break-up time, 45%; Schirmer test, 51%). Tear osmolarity also had the highest area under the receiver operating characteristic curve (0.89). Intereye differences in osmolarity were found to correlate with increasing disease severity (r(2) = 0.32).
  
  
  CONCLUSIONS
  Tear osmolarity is the best single metric both to diagnose and classify dry eye disease. Intereye variability is a characteristic of dry eye not seen in normal subjects.
authors.affiliation: Department of Ophthalmology, Georgetown University, Washington, DC, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lemp
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bron
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
authors.forename: José M
authors.initials: JM
authors.lastname: Benítez Del Castillo
authors.forename: David
authors.initials: D
authors.lastname: Geffen
authors.forename: Joe
authors.initials: J
authors.lastname: Tauber
authors.forename: Gary N
authors.initials: GN
authors.lastname: Foulks
authors.forename: Jay S
authors.initials: JS
authors.lastname: Pepose
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Sullivan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003941:Diagnostic Techniques, Ophthalmological; D015352:Dry Eye Syndromes / Q000145:classification / Q000175:diagnosis* / Q000628:therapy*; D005260:Female; D015590:Fluorophotometry; D006801:Humans; D007765:Lacrimal Apparatus / Q000737:chemistry; D008297:Male; D008537:Meibomian Glands / Q000737:chemistry; D008875:Middle Aged; D009994:Osmolar Concentration; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D013666:Tears / Q000737:chemistry*; D055815:Young Adult