title: An objective approach to dry eye disease severity.
abstract: OBJECTIVE
  A prospective, multisite clinical study (10 sites in the European Union and the United States) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease severity.
  
  
  METHODS
  Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population, 299 of which qualified with complete datasets. Osmolarity testing, Schirmer test without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire, the Ocular Surface Disease Index (OSDI), was also administered to each patient. Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated.
  
  
  RESULTS
  Osmolarity was found to have the highest correlation coefficient to disease severity (r(2) = 0.55), followed by conjunctival staining (r(2) = 0.47), corneal staining (r(2) = 0.43), OSDI (r(2) = 0.41), meibomian score (r(2) = 0.37), TBUT (r(2) = 0.30), and Schirmer result (r(2) = 0.17). A comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined normal and dry eye groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds.
  
  
  CONCLUSIONS
  Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories. Other tests were found to be informative in the more severe forms of disease; thus, clinical judgment remains an important element in the clinical assessment of dry eye severity. The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs. (ClinicalTrials.gov number, NCT00848198.).
authors.affiliation: TearLab Corp., San Diego, CA 92121, USA. bdsulliv@tearlab.com
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Sullivan
authors.forename: Diane
authors.initials: D
authors.lastname: Whitmer
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Nichols
authors.forename: Alan
authors.initials: A
authors.lastname: Tomlinson
authors.forename: Gary N
authors.initials: GN
authors.lastname: Foulks
authors.forename: Gerd
authors.initials: G
authors.lastname: Geerling
authors.forename: Jay S
authors.initials: JS
authors.lastname: Pepose
authors.forename: Valerie
authors.initials: V
authors.lastname: Kosheleff
authors.forename: Allison
authors.initials: A
authors.lastname: Porreco
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lemp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D018450:Disease Progression; D015352:Dry Eye Syndromes / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011446:Prospective Studies; D012720:Severity of Illness Index; D013666:Tears / Q000737:chemistry*; D055815:Young Adult
chemical_list: D015415:Biomarkers