Introduction
Dry eye disease is a multifactorial ocular condition that results from an inadequate quantity of tear film and/or a disturbance of tear film stability. In 2007, the International Dry Eye Workshop subcommittee for definition and classification expanded the definition of dry eye disease, beyond tear deficiency and evaporation, to include tear film degradation and potential damage to the ocular surface.1 Additionally, this subcommittee recognized the contributions to the disease process of hyperosmolarity of the tear film and inflammation of the ocular surface.1
The moisture of the eye is maintained by the tear film, which consists of an aqueous layer (secreted by the lacrimal glands), a mucus layer (produced by conjunctival goblet cells and by corneal and conjunctival epithelial cells), and a lipid layer (secreted primarily by the meibomian glands).2-4 Any alterations in the volume, composition, distribution, and/or clearance of the tear film can lead to dry eye disease. Based on etiology, dry eye can be categorized as aqueous tear-deficient or evaporative. Aqueous tear-deficient dry eye may be a result of Sjögren’s syndrome (primary disease or secondary to other autoimmune diseases, such as rheumatoid arthritis or systemic lupus erythematosus) or non-Sjögren factors, including lacrimal gland insufficiency, lacrimal duct obstruction, or reflex hyposecretion. Evaporative dry eye may also be caused by several factors including, but not limited to, meibomian gland dysfunction, eyelid aperture disorders or lid/globe incongruity, blink disorders, and ocular surface disorders.2,5
The global prevalence of dry eye, estimated from large studies, ranges widely from approximately 5% to 35%.6 Patients who suffer from dry eye have varying levels of symptoms, such as ocular dryness, burning, photophobia, foreign body sensation, grittiness, and redness, and may or may not have clinically meaningful signs, such as rapid tear film breakup time, increased osmolarity, and increased ocular surface staining.7,8 Individuals with dry eye also commonly experience disturbances in visual function, which have considerable negative impacts on their ability to carry out daily tasks (eg, driving and participating in sports and other leisure activities, such as reading and cooking).9 Since these limitations also have negative effects on overall quality of life, therapies that provide relief from the symptoms of dry eye are also likely to provide beneficial effects related to daily functioning and quality of life.10
The most common cause of evaporative dry eye disease is meibomian gland dysfunction, a condition associated with lipid insufficiency and/or poor lipid spreading, which results in a failure to form a continuous and homogeneous tear film. Ultimately, this failure leads to increased aqueous tear evaporation and decreased tear film stability.11,12 Although the evaporation rate of the tear film is determined by multiple factors, including the protein constituents of the tear film, the mucin coating of the epithelial cells, and the aqueous component of lacrimal secretions, the status of the lipid layer is critical.11 In particular, the thickness of the lipid layer affects evaporation and a thicker tear film lipid layer is correlated with better tear film stability.13-15 Further, a recent study showed that the thickness of the lipid layer, as measured by interferometry, is well correlated with dry eye symptoms in routine clinical practice.16 Thus, an important feature of any dry eye therapy intended to provide relief to patients with meibomian gland dysfunction is the ability to mimic the lipid layer of the tears.