Changes in the tear film and ocular surface from dry eye syndrome
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.
References (310)
- et al.
Androgen control of autoimmune expression in lacrimal glands of MRL/Mp-lpr/lpr mice
Clin. Immunol. Immunopathol.
(1989) - et al.
Efficacy and tolerability outcomes after punctal occlusion with silicone plugs in dry eye syndrome
Am. J. Ophthalmol.
(2001) - et al.
Inflammatory cytokines in the tears of patients with ocular rosacea
Ophthalmology
(1997) The pathology of dry eye
Surv. Ophthalmol.
(2001)- et al.
An intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling
J. Biol. Chem.
(1999) - et al.
Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils
J. Biol. Chem.
(1996) - et al.
Ocular mucinspurification, metabolism and functions
Prog. Retin. Eye Res.
(1997) Blinking and the mechanics of the lacrimal drainage system
Ophthalmology
(1981)- et al.
Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissueevidence for a regulatory function of nerve growth factor in vivo
Neuroscience
(1992) - et al.
Lipid synthesis in vitro by rabbit meibomian gland tissue and its inhibition by tetracycline
Biochim. Biophys. Acta.
(1990)
Identification of a nonlysozymal bactericidal factor (beta lysin) in human tears and aqueous humor
Am. J. Ophthalmol.
Primary Sjogren syndromeclinical and immunopathologic features
Semin. Arthritis Rheum.
Immunological and electrophoretic studies of human tear proteins
Exp. Eye Res.
Morphologic effect of hyperosmolarity on rabbit corneal epithelium
Ophthalmology
Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation
Am. J. Ophthalmol.
Mucin genes expressed by the ocular surface epithelium
Prog. Ret. Eye Res.
Corneal epithelial permeability of dry eyes before and after treatment with artificial tears
Ophthalmology
Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction
Ophthalmology
Lacrimal gland epithelial cells stimulate proliferation in autologous lymphocyte preparations
Exp. Eye Res.
Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha
J. Invest. Dermatol.
Formation and rupture of the tear film
Exp. Eye Res.
Wettability and wetting of corneal epithelium
Exp. Eye Res.
Tear physiology and dry eyes
Surv. Ophthalmol.
Effects of subminimal inhibitory concentrations of minocycline on neutrophil chemotactic factor production in comedonal bacteria, neutrophil phagocytosis and oxygen metabolism
Arch. Dermatol. Res.
A novel mechanism of action of tetracyclineseffects on nitric oxide synthases
Proc. Natl. Acad. Sci. USA
MUC16 mucin is expressed by the human ocular surface epithelia and carries the H185 carbohydrate epitope
Invest. Ophthalmol. Vis. Sci.
Hypophysectomy-induced regression of female rat lacrimal glandspartial restoration and maintenance by dihydrotestosterone and prolactin
Invest. Ophthalmol. Vis. Sci.
Androgen support of lacrimal gland function
Endocrine
Essential ions for maintenance of the corneal epithelial surface
Invest. Ophthalmol. Vis. Sci.
Silicone rubber contact lenses for the compromised cornea
Cornea
Self-reported assessment of dry eye in a population-based setting
Invest. Ophthalmol. Vis. Sci.
Mucin biophysics
Annu. Rev. Physiol.
Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component
Cornea
Neutrophil defensins induce histamine secretion from mast cellsmechanisms of action
J. Immunol.
DREI study group. Results of a dry eye questionnaire from optometric practices in North America
Adv. Exp. Med. Biol.
The instilled fluid dynamics and surface chemistry of the tear film
Invest. Ophthalmol. Vis. Sci.
Keratoconjunctivitis sicca and primary Sjogren's syndrome in a Danish population aged 30–60 years
Acta. Ophthalmol. Scand.
Tears and the lacrimal gland
Sci. Am.
Functional innervation of the lacrimal gland in the cat. Origin of secretomotor fibers in the lacrimal nerve
Arch. Ophthalmol.
Electrolytes in lacrimal gland fluid and in tears at various flow rates in the rabbit
Am. J. Physiol.
Symptomatology of HEMA contact lens wear
Optom. Vis. Sci.
Tear lactoferrina bacteriostatic and complexing protein
Invest. Ophthalmol.
The Doyne Lecture. Reflections on the tears
Eye
The ocular surface in keratoconjunctivitis sicca
Eye
The meibomian glands and tear film lipids. Structure, function, and control
Adv. Exp. Med. Biol.
Developmental mucin gene expression in the human respiratory tract
Am. J. Respir. Cell. Mol. Biol.
Constitutive and regulated secretion of proteins
Annu. Rev. Cell Biol.
Influence of diet on tear function
Optom. Vis. Sci.
CANDEES. The Canadian dry eye epidemiology study
Adv. Exp. Med. Biol.
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