Diagnostic performance of a tear protein panel in early dry eye

To evaluate the tear protein pattern in patients with recent subjective symptoms of dry eye (DE) and with poor distinctive DE clinical signs.

One hundred sixty patients suspected of suffering from mild to moderate DE according to the Dry Eye Workshop (DEWS report 2007) severity grade and 45 matched normal volunteers were included in the study. Subjective symptom score (Ocular Surface Disease index score), Schirmer test I, tear film break-up time, cornea and conjunctiva staining (National Eye Institute score); and tear protein analysis were performed. Statistical evaluation of data was performed with Mann-Whitney unpaired and Student t tests, (significance p<0.05). Correlations between variables were evaluated by using Pearson's (r) or Spearman's (ρ) correlation coefficients. Thresholds were selected from receiver operating curves; sensitivity, specificity, likelihood ratio (LR+), and positive predictive values were calculated for each protein. The combination of variables was carried out by univariate analysis, representing the best combination of tests for early DE diagnosis.

TOTAL PROTEIN CONTENT (TP) AND THE FOLLOWING PROTEINS WERE RECOGNIZED IN ALL SAMPLES: lysozyme-C (LYS-C), lactoferrin (LACTO), tear lipocalin 1 (LIPOC-1), zinc-alpha-2-glycoprotein (ZAG-2), transferrin (TRANSF), and exudated serum albumin (ALB). A statistically significant decrease was demonstrated between normal subjects and patients with DE (mg/ml, mean±SD) for TP (9.89±2.28 versus 6.44±2.1), LYS-C (3.06±1.07 versus 2.15±0.78), LIPOC-1 (1.71±0.52 versus 0.98±0.5), ZAG-2 (0.43±0.24 versus 0.25±0.2), TRANSF (0.9±0.6 versus 0.33±0.3), and LACTO (2.11±0.74 versus 1.47±0.76), while an increase was found for ALB (0.21±0.5 versus 0.94±1.28). LIPOC-1 and ZAG-2 were strongly correlated to tear film break-up time. The proteins were related to the DEWS severity grade. Changes in each protein were a better predictor of early DE than were clinical variables; TP, LIPOC-1, and ALB exhibited the highest diagnostic performance either alone (LR+ 16.7, 12.3, 4.7, respectively) or when combined in a univariate analysis (LR+: 41.8, positive predictive value: 99.9).

Our results demonstrated in tears from patients with early DE a significant reduction in tear protein content as a whole, associated with a decrease in proteins with antibacterial and protective functions. A decrease in proteins with lipid binding properties and an increase in inflammatory-related proteins were also shown. Changes in the abundance of a panel of tear proteins with divergent functions was found to better diagnose early DE than did conventional clinical tests.