Profile of Cytokines in the Tear Fluid of Patients With Dry-Eye Disease

Abstract

Purpose: : Dysfunction of the lacrimal functional unit alters the balance of tear film components that stabilize the tear film and support and protect the ocular surface. It is now recognized that these changes in tear composition promote inflammation on the ocular surface by several mechanisms. On the one hand there may be decreased secretion of natural antiinflammatory factors. On the other hand there appears to be increased production of certain proinflammatory cytokines and proteolytic enzymes by stressed ocular surface, glandular epithelial cells as well as by the inflammatory cells that infiltrate these tissues.Changes in cytokine concentrations could be an important diagnostic tool as indicators of ocular surface health in keratokonjunctivitis sicca and other ocular surface diseases. The aim of this prospective, non-randomized, clinical, single-centre study was to assess the changes in the cytokine concentrations in tear samples of patients with keratokonjunctivitis sicca compared to healthy controls.

Methods: : 50 patients with severe keratokonjunctivitis sicca (18 patients with tear-deficient dry eye and 32 patients with evaporative dry eye) and 50 controls were enrolled in the trial. Tear samples were analyzed by cytometric bead-based assay (CBA) which pairs the high specificity and sensitivity of sandwich ELISA with the versatility of flow cytometry, allowing multiple immunoassays to be run simultaneously on the surface of small microspheres. This enables the determination of multiple unknown analyte concentrations from a single, small tear sample. All statistical analyses were performed using Statistica^TM software, p-values < 0.05 *, < 0.001** were considered significant.

Results: : There were significant higher cytokine concentrations (IL-4, IL-6, IL-8, IL-1 alpha, IP10) in tear samples of patients with keratokonjunctivitis sicca compared to the control group. In the patients with tear-deficient dry eye there were mostly higher concentrations of cytokines than in the patients with evaporative dry eye. However, these results were only significant for IL-4.

Conclusions: : Tear cytokine concentrations can be determined using cytometric bead-based assay. Our results support the inflammatory pathogenesis in dry eye disease and suggest to put more emphasis on antiinflammatory and immunosuppressive drugs in the therapy of these patients.

Keywords: cornea: tears/tear film/dry eye • cytokines/chemokines • inflammation