Evaluation of Tear Film Urea Level as a Diagnostic Marker of Dry Eye Disease: A Pilot Study

Introduction Urea secreted in the sweat is important for skin moisture. Similarly, ocular surface moisture is maintained by the conjunctiva. Based on this, the level of urea in tear film can be used as a potential diagnostic test for dry eye disease (DED). One of the standard tests for DED is Schirmer's test (ST). The aim of this study was to compare tear film urea to values of ST. Methods Fifty patients symptomatic for DED having ST <= 10 mm/5 min were enrolled in the study. Fifty age-and sex-matched asymptomatic subjects with ST 10 mm/5 min were taken as controls. All patients were subjected to an estimation of tear film urea, collected using micropipettes, and analyzed by an Erba Chem 5 semi-autoanalyzer. Based on the ST reading as per the Dry Eye Workshop 2007 (DEWS) classification, dry eye was classified as dry eye (<= 10 mm/5 min), severe dry eye (<= 5 mm/5 min), and very severe dry eye (<= 2 mm/5 min). Tear film urea values were compared with ST values that were considered standard. Statistical analysis was done using Medcalc version 19.7. A p-value < 0.05 was considered significant. Results The mean tear film urea levels in cases were (26.78 +/- 5.70 mg/dL) significantly lower compared with controls (41.72 +/- 6.86 mg/dL). The area under the receiver characteristic operator curve (AUC) for tear film urea in diagnosing DED was 0.936 (p <0.0001) with a cutoff of <= 37.2 mg/dL, yielding a sensitivity of 96% and a specificity of 76%. For diagnosing severe DED, the AUC for tear film urea was 0.824 (p <0.0001) with a cutoff value of <= 23.4 mg/dL, yielding a sensitivity of 60.8% and a specificity of 92.59%. For diagnosis of very severe DED, the AUC for tear film urea was 0.972 (p <0.0001) with a cutoff value of <= 19.8 mg/dL, yielding a sensitivity of 100% and a specificity of 93.62%. On comparing ST values to tear film urea, the regression coefficient was 0.85 (p < 0.0001), suggesting a linear relationship between ST and tear film urea. Conclusion The study demonstrates that tear film urea can be a potential diagnostic marker for DED. The study also indicates that tear film urea level is linearly related to Schirmer's test values and provides an approximate diagnostic cutoff level for the design of future large-scale studies.