Changes in the tear film and ocular surface from dry eye syndrome

https://doi.org/10.1016/j.preteyeres.2004.04.003Get rights and content

Abstract

Dry eye syndrome (DES) refers to a spectrum of ocular surface diseases with diverse and frequently multiple aetiologies. The common feature of the various manifestations of DES is an abnormal tear film. Tear film abnormalities associated with DES are tear deficiency, owing to insufficient supply or excessive loss, and anomalous tear composition. These categorizations are artificial, as in reality both often coexist. DES disrupts the homeostasis of the tear film with its adjacent structures, and adversely affects its ability to perform essential functions such as supporting the ocular surface epithelium and preventing microbial invasion. In addition, whatever the initial trigger, moderate and severe DES is characterized by ocular surface inflammation, which in turn becomes the cause and consequence of cell damage, creating a self-perpetuating cycle of deterioration.

Progress has been made in our understanding of the aetiology and pathogenesis of DES, and these advances have encouraged a proliferation of therapeutic options. This article aims to amalgamate prevailing ideas of DES development, and to assist in that, relevant aspects of the structure, function, and production of the tear film are reviewed. Additionally, a synopsis of therapeutic strategies for DES is presented, detailing treatments currently available, and those in development.

Introduction

Dry eye syndrome (DES) refers to a common but highly heterogeneous group of ocular surface disorders (Dana and Hamrah, 2002; Schaumberg et al., 2002). Precise determination of the prevalence of DES is hampered by the lack of agreed diagnostic criteria; in part due to the wide spectrum of conditions the term encompasses, the large variation in disease severity, and the nonspecificity of its associated symptoms and clinical signs. Despite this limitation, most large studies, using a variety of definitions, have estimated the prevalence of “significant” DES to be about 10–20% in the adult population, though fortunately severe DES is less frequent (Hikichi et al., 1995; Bjerrum, 1997; Doughty et al., 1997; Bandeen-Roche et al., 1997; Caffery et al., 1998; McCarty et al., 1998; Schein et al., 1999; Moss et al., 2000; Begley et al., 2002; Chia et al., 2003; Lin et al., 2003; Schaumberg et al., 2003).

The term “dry eye” gives the impression that DES is exclusively caused by dryness, but the aetiology is not that straightforward (Tsubota, 2002). Simple desiccation is not the only pathogenic mechanism involved (Lemp et al., 1970), thus prevention of desiccation in isolation is inadequate in the management of the condition, explaining the frequently encountered limitations of artificial tears that serve only to wet the eye. Common features of DES include ocular surface epitheliopathy, tear hyperosmolality, an unstable preocular tear film, varying degrees of inflammation, and symptoms of ocular irritation (Lemp, 1995). This article presents the contemporary thinking on the aetiology, pathogenesis, and management of DES; and to assist in that, relevant aspects of the structure, function, and production of the tear film will be briefly reviewed.

Section snippets

Tear film thickness and structure

The preocular tear film has traditionally been described as a trilaminar structure, predominantly consisting of a watery aqueous phase, overlying a thin mucous layer, with a superficial coating of lipid (Wolff, 1946; Holly and Lemp, 1977). Early estimates of tear film thickness were based on invasive tests, such as placing glass fibres against the cornea (Mishima, 1965), measuring fluorescence after instilling fluorescein (Mishima, 1965; Benedetto et al., 1975), or applying absorbent paper to

Tear film production

The quantity and composition of tear film secretions are determined by complex interactions between the autonomic nervous and endocrine systems, and locally acting cytokines.

The endocrine system and the tear film

Most epidemiological studies report that DES is more common in females, particularly after the onset of the menopause, and/or if associated with autoimmune disease (Doughty et al., 1997; Caffery et al., 1998; McCarty et al., 1998; Moss et al., 2000; Chia et al., 2003; Lin et al., 2003; Schaumberg et al., 2003), although not all studies have found significant gender asymmetry (Bjerrum, 1997; Schein et al., 1997). A greater prevalence of DES in females suggests that sex hormones are involved in

Aetiology and pathogenesis of DES

DES is often initiated by, and by definition associated with, inadequate ocular lubrication as a result of impaired lacrimal function, failure in the transfer of lacrimal fluid into the conjunctival sac, and/or excessive tear evaporation (Lemp, 1995). However, the pathogenesis of its consequent ocular surface disease is not only desiccation, but involves tear film hyperosmolality, lack of supportive factors, and inflammation. The tear film, epithelia of the cornea and conjunctiva, the lacrimal

Diagnosis of DES

The diagnosis of DES is complicated in that there are not two separate, distinct groups of patients, with and without DES, but sliding scales of susceptibility, frequency of occurrence, and severity. This is evident from the finding that symptoms and signs of DES can be induced by environmental manipulation in people who, most clinicians would agree, do not have DES.

The variety of DES clinical manifestations also means that there is not one single diagnostic test. The 1995 National Eye

Management of DES

When the complexity of the tear film and ocular surface functional unit, and importance of inflammation in DES are realized, it becomes obvious why artificial tears that serve only to wet the eye are inadequate in all but the mildest of situations. Ideally, the cause of DES for each patient should be determined and treated, but traditional therapies do not cure the disease, or even directly target its causes. Additionally, the aetiology of DES is frequently complex, with several interacting

Conclusions and future directions

The structure and function of the tear film is far from being understood. There is still debate about fundamental issues, such as the quantity and importance of ocular mucins and the processes involved in tear rupture. It is a prerequisite that the normal tear film is better understood if we are to move on in our ability to effectively manage DES. That stated, advances in lacrimology are beginning to show signs of fruition, with DES treatments emerging that verge on the revolutionary. More

Acknowledgements

The authors would like to thank Dr. Ian Pearce (Glasgow Caledonian University) for his helpful comments during the writing of this manuscript. This work was supported by a research scholarship from Ultralase Ltd.

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