Present Understanding Of Dry Eye Disease And Implications For Therapy

A recent international workshop designed to collate and critique in an evidence-based manner the accumulated knowledge concerning dry eye disease and its treatment published a comprehensive report in 2007.1 The Dry Eye Workshop provided guidance to clinicians and researchers regarding the definition, classification, epidemiology, and research findings, and treatment guidelines for dry eye disease.

The consensus definition of dry eye disease was stated to be that dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.2 This definition expands the scope of the disease to include effects on visual acuity and discomfort and damage to the ocular surface through both inflammation of the tissues and hyperosmolarity of the tear film.3

The classification of dry eye disease proposed three distinct schemas: (1) an etio-pathologic, (2) a mechanistic, and (3) a severity-based description.2 Fig. 1 depicts the etiopathologic classification and identifies both an aqueous-production deficit and an evaporative category of dry eye disease. Although clinical expression of either

Supported by an unrestricted grant from Research to Prevent Blindness, New York, NY. Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 East Muhammad Ali Boulevard, Louisville, KY 40202, USA E-mail address: [email protected]

Rheum Dis Clin N Am 34 (2008) 987-1000


0889-857X/08/$ - see front matter © 2008 Elsevier Inc. All rights reserved.

Nomenclature Eye Picture
Fig. 1. Etiopathologic classification of dry eye disease. (From Ethis Communications. Report of the International Dry Eye Workshop. Ocul Surf 2007;5:77; with permission.)

one or the other type of dry eye is possible, the most common occurrence is a combination of the two types, suggesting that treatment options need to address both mechanisms of disease. The mechanistic schema describing dry eye disease is portrayed in Fig. 2, which details the extensive interactivity and cyclical effects of hyperosmolarity of the tear film, instability of the tear film, and inflammatory activity of the ocular surface system. The severity-based classification is described in Table 1 and illustrates that sequential changes in the degree of discomfort, instability of the tear film, increasing signs of inflammation, and evolving damage to the ocular surface indicate progressive disease. Based on this analysis of the nature and clinical manifestation of dry eye, recommendations for therapy have been made.4 The implications of this assessment of dry eye are significant for all patients with dry eye but particularly patients with Sjogren's syndrome, because the severity of dry eye disease and the role of inflammation in the pathogenesis of the Sjogren's syndrome-related dry eye is particularly prominent in those patients.5

Review of the epidemiology of dry eye disease also reveals information about the underlying predispositions to the disease and its association with age, gender, and general health. Dry eye disease is more common in women than men; increases with advancing age; and often is associated with changes in hormone levels, particularly androgenic hormones.6-11 The association of dry eye with systemic disease of immune-mediated pathogenesis has also been well documented, Sjogren's syndrome being the prime example.12 Although the prevalence of dry eye varies widely across international populations from a reported high of 38% in some Asian studies to more consistent reports of 12% to 15% in North American populations above age 55, the projected number of affected patients is considerable.13-16 Increasing awareness of the prevalence of dry eye disease and the quality-of-life changes it produces alerts to the fact that the frequency of the condition is increasing as the population

Dry Eye Syndrome
Fig. 2. Mechanistic classification of dry eye disease. (From Ethis Communications. Report of the International Dry Eye Workshop. Ocul Surf 2007;5:85; with permission.)

ages and as women outlive men. It is now recognized as an ever more important public health issue.17

The present understanding of the pathogenesis of dry eye disease also has implications for management and therapy. Although once considered only a lack of tears on the ocular surface, the disease is now recognized as a complex and multifactorial process with interaction of not only low volume of tear fluid, but also instability of the tear film with subsequent hypertonicity of the preocular fluid that is able not only directly to damage surface epithelial cells but also to provoke and stimulate inflammatory reaction in the ocular tissues.18-20 Accumulation of inflammatory T lymphocytes in the lacrimal and subconjunctival tissue is associated with release of proinflammatory cytokines and matrix-metalloproteinases in both tears and tissues.21-25 The observation that such inflammatory processes can be mitigated by topical anti-inflammatory treatments, such as corticosteroids and immunomodulating agents, opens the door to additional therapeutic strategies.26-30


It is ironic that the first description of keratoconjunctivitis sicca in Sjogren's syndrome was that of an inflammatory disease, yet the subsequent emphasis became the lack of tear fluid on the eye.31 The recognition that keratoconjunctivitis sicca (dry eye) occurred commonly in patients with rheumatoid arthritis and Sjogren's syndrome and that the severity of the disease was greater than non-Sjogren's-associated dry eye has led to other aspects of inflammation occurring with dry eye.32,33 The increased prevalence of meibomian gland disease and the evaporative form of dry eye has been documented in Sjogren's syndrome patients.34 These findings carry therapeutic implications.

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