discovering dry eye
An Inflammatory Tear
BY JASON J. NICHOLS, OD, MPH, PHD
In general, the immune system's function is to protect the body from tissue damage or infectious diseases. The body has several innate immune responses that help to protect it from
tissue damage including several secretions of the body such as the tear film.
While several of these innate mechanisms help to protect the eye and ocular surface, etiological factors associated with dry eye disease do exist and can result in an ocular immune response.
For instance, ocular surface desiccation because of tear film insufficiency or even contact lens wear could stimulate the response. Researchers believe that excessive evaporation of the tear film, by way of an altered lipid layer, leads to
hyperosmolarity, which might stimulate the ocular surface in terms of the inflammatory cascade. Further, the lacrimal gland may release proinflammatory mediators associated with the inflammatory response.
The Inflammatory Response
Regardless of the source, additional mediators in somewhat of a cascading cycle will further enable the initial inflammatory response. For instance, the conjunctival vasculature can release leukocytes (white blood cells) and are phagocytic to antigens. Lymphocytes are antigen-specific leukocytes and are responsible for adaptive immunity.
Examples of leukocytes that aren't antigen-specific include both macrophages and polymorphonuclear leukocytes, both of which act by binding molecules on the surfaces of pathogens. Macrophages produce small protein molecules called cytokines in response to an immune stimulus.
The Cytokine Connection
More specific to the eye, cytokines have been associated with changes in mucus secretion and ocular surface hypoesthesia and
keratinization. Some examples of cytokines present in the tear film include interleukin-1 (IL-1) and tumor necrosis factor-*(TNF-*). Some of the cytokines are considered inactive in the tear fluid, but a concurrent increase in tear film osmolarity with dry eye disease may result in their activation, although this requires further study.
The contemporary understanding of the role of inflammation in dry eye disease has lead to the development of treatment strategies aimed at targeting the inflammatory process. Such treatments have included topical
corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), topical immunosuppressants
(cyclosporine A), tetracycline derivatives and autologous serum.
Corticosteroids are potent and work by inhibiting cytokine activation. Although studies have shown that these agents are beneficial in the short-term in improving signs and symptoms associated with dry eye disease, longer term studies of "mild" steroids are needed to better determine their safety and efficacy. Initial studies with traditional NSAIDs haven't yielded efficacy for dry eye treatment. Cyclosporine A primarily inhibits
T-cell and cytokine activation. Recent evidence has suggested that tetracyclines decrease cytokines (IL-1), nitric oxide and matrix
metalloproteinase. Autologous serum also works by inhibiting inflammatory cytokines and has shown promise in treating severe dry eye disease in several studies.
Interestingly, all of the anti-inflammatory treatments discussed here have an impact on the important cytokines that are present on the ocular surface.
Pursuing a Solution
Future studies should help further elucidate the inflammatory processes of dry eye disease, including the role of contact lenses in stimulating an inflammatory response of the eye and ocular surface.
For now, it's clear that our profession is making progress in understanding this disease.
Dr. Nichols is an assistant professor of Optometry and Vision Science at The Ohio State University College of
Contact Lens Spectrum, Issue: January 2005