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

Sullivan, Benjamin D. PhD; Crews, Leslie A. PhD; Sönmez, Barş MD; de la Paz, Maria F. MD; Comert, Ebru MD; Charoenrook, Victor MD; de Araujo, Aline L. MD; Pepose, Jay S. MD, PhD; Berg, Michael S. BA; Kosheleff, Valerie P. MS; Lemp, Michael A. MD

doi: 10.1097/ICO.0b013e318242fd60
Clinical Science

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.

*TearLab Corporation, San Diego CA

Department of Ophthalmology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey

Centro de Oftalmologia Barraquer, Barcelona, Spain

§Pepose Vision Institute, St Louis, MO

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO

Department of Ophthalmology, Georgetown University, Washington, DC

**Department of Ophthalmology, George Washington University, Washington, DC.

Reprints: Benjamin D. Sullivan, TearLab Corporation, 7360 Carroll Rd, Suite 200, San Diego CA (e-mail: bdsulliv@mac.com).

This study was supported by TearLab Corporation, San Diego, CA. The authors wish to indicate the following financial interests in TearLab Corporation: Consultant (M.A.L., L.A.C.), Equity (M.A.L., M.S.B., J.S.P.), Patents (B.D.S.), Employee (B.D.S., M.S.B., V.P.K.). B.S., M.F.P., E.C., V.C., and A.L.A. have no financial interests to disclose.

Principal investigators for participating sites were B.S. and M.F.d.l.P.

Received March 31, 2011

Accepted November 10, 2011

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.