The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options

J Ocul Pharmacol Ther. 2020 Apr;36(3):137-146. doi: 10.1089/jop.2019.0060. Epub 2020 Mar 12.

Abstract

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making.

Keywords: T cells; dry eye disease; goblet cells; immune dysregulation; immunology; inflammation; integrin protein; intercellular adhesion molecule 1 (ICAM-1); lymphocyte function-associated antigen 1 (LFA-1); ocular surface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Topical
  • Clinical Decision-Making / ethics
  • Cyclosporine / administration & dosage
  • Cyclosporine / therapeutic use
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / immunology
  • Dry Eye Syndromes / pathology
  • Dry Eye Syndromes / prevention & control*
  • Goblet Cells / immunology
  • Goblet Cells / physiology
  • Homeostasis / physiology*
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Inflammation / drug therapy
  • Integrins / immunology
  • Intercellular Adhesion Molecule-1 / immunology
  • Lacrimal Apparatus / physiopathology
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Phenylalanine / administration & dosage
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / therapeutic use
  • Steroids / administration & dosage
  • Steroids / therapeutic use
  • Sulfones / administration & dosage
  • Sulfones / therapeutic use
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology
  • Tears / drug effects
  • Tears / immunology*
  • Tears / physiology

Substances

  • Immunologic Factors
  • Immunosuppressive Agents
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • Steroids
  • Sulfones
  • lifitegrast
  • Intercellular Adhesion Molecule-1
  • Phenylalanine
  • Cyclosporine