Elsevier

Ophthalmology

Volume 124, Issue 11, Supplement, November 2017, Pages S14-S19
Ophthalmology

Original article
Inflammation in Dry Eye Disease: How Do We Break the Cycle?

https://doi.org/10.1016/j.ophtha.2017.08.029Get rights and content

This article reviews the literature and summarizes the role of inflammation in dry eye disease. A PubMed search was performed using the keywords inflammatory cycle and dry eye. All searches were limited to articles published in or translated into the English language, dating from 1973 through March 2017. There were no restrictions on the study design. Advances in understanding the pathogenesis of dry eye disease has revealed that inflammation is a core driver: the so-called “vicious circle” of inflammation. Researchers continue to analyze the precise mechanisms by which inflammation occurs. This has led to therapeutic options to break the cycle. Continued animal and human studies reveal other potential sites for treatment in this complex host of disorders.

Section snippets

Establishment of Inflammation's Critical Role in Dry Eye Disease

Dry eye disease (DED) is a heterogeneous disorder of the ocular surface in which the common denominator is inflammation. The recognition of inflammation as a critical driver is reflected by its inclusion in the Dry Eye Workshop1 definition of DED: “Dry eye disease is a multifactorial disorder of the tears and ocular surface, associated with symptoms of discomfort, visual disturbance, and tear film instability. It is accompanied by increased osmolarity of the tear film and inflammation of the

Neuronal Feedback Loop

The lacrimal functional unit, defined as the ocular surface, lacrimal gland, and their neural interconnectivity, maintains ocular surface homeostasis, and disruption of this leads to tear film instability.1, 5 Tear production is regulated through a neural reflex loop; stimulation of nerves at the ocular surface or nasal mucosa sends impulses to the brain via the fifth cranial nerve, triggering a reflex response via nerves passing to the lacrimal glands. Pain, microbial or environmental insult,

Players in the “Vicious Circle” of Inflammation

The inflammatory cycle consists of afferent and efferent arms (Figs 1 and 2).1, 9, 10, 25 The afferent arm consists of stress to the ocular surface (environmental, endogenous, microbial, or a combination thereof, as well as hormone imbalance and genetic factors). When there is excess stress, production of cytokines, matrix metalloproteinases (MMPs), and chemokines ensues. This inflammatory setting prompts the maturation of antigen-presenting cells (APCs) and resident dendritic cells in the

How Do We Break the Inflammatory Cycle?

To date, 2 commercially available topical medications have emerged based on the recognition of inflammation as the fundamental driver of DED. Topical cyclosporine 0.05% was approved by the United States Food and Drug Administration in 2002. Cyclosporine acts as a T-cell inhibitor and also decreases expression of HLA-DR (a major histocompatibility complex class II cell surface receptor involved in antigen presentation) and IL-6.31, 32 Several studies consistently have shown improvement in signs

Conclusions

Dry eye disease is a heterogeneous disorder of the ocular surface in which the common denominator is inflammation; it is both a cause and effect of the disease. Currently, 2 Food and Drug Administration–approved medications (topical cyclosporine 0.05% and topical lifitegrast 5%) are directed at the inflammatory component of DED. Many therapeutic targets in the inflammatory cascade have been identified, as evidenced by the numerous mechanisms of action of various medications being studied.

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    Statement of Potential Conflict of Interest and Funding/Support: See page S19.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): M.K.R.: Consultant – The Eye-Bank for Sight Restoration; Financial support – The Eye-Bank for Sight Restoration, Pentavision, Ophthalmology Management, Eurobio; Expert testimony – The Expert Institute; Equity owner – AMO, Gilead, Ophthotech

    F.S.M.: Consultant and speakers’ bureaus – Allergan and Shire.

    Author Contributions:

    Conception and design: Mah, Rhee

    Analysis and interpretation: Mah, Rhee

    Data collection: Mah, Rhee

    Obtained funding: none

    Overall responsibility: Mah, Rhee

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