title: Automated Tear Film Surface Quality Breakup Time as a Novel Clinical Marker for Tear Hyperosmolarity in Dry Eye Disease.
abstract: OBJECTIVE
  To assess the diagnostic performance of a novel, automated, noninvasive measure of tear film stability derived from Placido disc videokeratography, the tear film surface quality breakup time (TFSQ-BUT), as a clinical marker for diagnosing dry eye disease (DED) relative to a standard of tear hyperosmolarity.
  
  
  METHODS
  This prospective, cross-sectional study involved 45 participants (28 DED, 17 controls). Symptoms (Ocular Surface Disease Index) and signs (tear osmolarity, TFSQ-BUT, tear breakup time measured with sodium fluorescein [NaFl-BUT], ocular surface staining and Schirmer test with topical anesthesia) of DED were assessed. Three measures of TFSQ-BUT and NaFl-BUT were taken per eye; "first," "average," and "shortest" BUT were analyzed separately. Optimal diagnostic cutoff values were determined using the Youden Index. The repeatability and agreement of the TFSQ-BUT was compared with two clinicians who manually assessed noninvasive BUT (CNI-BUT). Repeatability of methods was assessed using the geometric coefficient of variation (gCoV, %). Agreement between methods was considered with Bland-Altman analysis.
  
  
  RESULTS
  Eyes with DED had significantly shorter TFSQ-BUTs than controls (P < 0.05). There was a significant, moderate correlation between both shortest and average TFSQ-BUT and NaFl-BUT (r = 0.35, P = 0.02 and r = 0.38, P = 0.01, respectively). The receiver-operator characteristic (ROC) curve for shortest TFSQ-BUT showed an area under the curve of 0.92 (P < 0.0001). Shortest TFSQ-BUT with a criterion of 12.1 seconds had a sensitivity of 82% and specificity of 94% for diagnosing DED against tear hyperosmolarity. Automated TFSQ-BUT showed less variability (gCoV = 9.4%, 95% confidence interval [CI]: 7.1%-14.0%) than CNI-BUT (gCoV = 27.0%, 95% CI: 19.62%-41.06%, P < 0.05).
  
  
  CONCLUSIONS
  Automated TFSQ-BUT is a repeatable, noninvasive clinical marker with both high sensitivity and specificity for tear hyperosmolarity.
authors.forename: Laura Elizabeth
authors.initials: LE
authors.lastname: Downie
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003941:Diagnostic Techniques, Ophthalmological; D015352:Dry Eye Syndromes / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D013666:Tears / Q000737:chemistry*; D055815:Young Adult