Clinical Utility of Objective Tests for Dry Eye Disease: Variability Over Time and Implications for Clinical Trials and Disease Management

Purpose: To evaluate the efficacy of commonly used biomarkers in dry eye disease management in a longitudinal observational case series study followed by an interventional study in a subset of subjects treated with cyclosporine A (0.05%). Methods: Bilateral tear osmolarity, Schirmer, tear film breakup time (TBUT), staining, meibomian grading, and Ocular Surface Disease Index were measured for a period of 3 consecutive months in participants recruited from a clinic-based population at 2 study sites. Fifty-two subjects completed the study (n = 16 mild/moderate, n = 36 severe; age, 47.1 +/- 16.1 years). After the 3-month observation period, severe dry eye patients were prescribed topical cyclosporine A and evaluated for an additional 3 months. Results: Tear osmolarity (8.7 +/- 6.3%) exhibited significantly less variability over a 3-month period than corneal staining (12.2 +/- 8.8%, P = 0.040), conjunctival staining (14.8 +/- 8.9%, P = 0.002), and meibomian grading (14.3 +/- 8.8%, P < 0.0001) across the entire patient population. Osmolarity also demonstrated less variation than TBUT (11.7 +/- 9.0%, P = 0.059), Schirmer tests (10.7 +/- 9.2%, P = 0.67), and Ocular Surface Disease Index (9.3 +/- 7.8%, P = 0.94), although the differences were not significant. Variation in osmolarity was less for mild dry eye patients (5.9 +/- 3.1%) than severe dry eye patients (10.0 +/- 6.9%, P = 0.038). After treatment, average osmolarity and variability were lowered from 341 +/- 18 mOsm/L to 307 +/- 8 mOsm/L (P, 0.0001, n = 10). A downward trend in symptoms followed changes in osmolarity, declining from 44 +/- 17 mOsm/L to 38 +/- 18 mOsm/L (P = 0.35). None of the other signs demonstrated a change after treatment. Conclusions: Over a 3-month period, tear film osmolarity was found to have the lowest variability among commonly used signs of dry eye disease. Reductions in osmolarity preceded changes in symptoms during therapy.