Medical Management of Dry Eye Disease
The initial management of dry eye disease relies on the use of artificial tear substitutes and the conservation of natural tears. Most artificial tears are lubricants with an electrolyte content that is only an approximation of normal tears. Viscosity agents are often added to artificial tears to increase the ocular surface residence time. An understanding of the complex interactions between aging, hormonal change, the environment, and the immune system has lead to new therapies to treat dry eye disease. Treatments that reduce associated conjunctival inflammation and stimulate the production of normal tear components may become increasingly important for the management of severe disease. An understanding of the behaviour of normal tears and the aetiology of dry eye is fundamental to the development of an effective treatment strategy.
Rational for Medical Management
Structure of the Tear Film
The tear film is part of a functional unit that comprises the tears, corneal and conjunctival epithelium, lacrimal glands, and lids. Disturbance of one or more of these interrelating structures can result in characteristic symptoms and signs of dry eye disease. This disease acts through the common disease mecha¬nisms of hyperosmolar tears and surface drying that damages the epithelial cells, with associated inflammation and a susceptibility to infection. The terms dry eye disease, dysfunctional tear syndrome, and keratoconjunctivitis sicca are synonymous.
Tears are mechanically spread over the ocular surface by upper lid blink¬ing, but the development of an effective tear film depends upon surfactant phospholipids in the surface layer and mucous in the basal layer that allows the fluid to adhere to the hydrophilic epithelial cells. The lubricating action of the tear film disperses the shearing forces on the epithelium caused by blinking. Finally, the tear film provides a smooth optical interface, transports metabo¬lites, and freely transmits oxygen and carbon dioxide to the cornea.
The structure of the tear film consists of an outer lipid layer lying on an aqueous layer that contains mucus. The meibomian glands secrete the lipid, which is released from the glands by lid movement. The lipid layer is composed of two phases: (1) an outer surface non-polar phase that contains waxes, choles¬terol esters, and triglycerides and (2) an inner polar aqueous-mucin phase that has surfactant properties. The inner polar phospholipids are bound to protein lipocalins within the aqueous layer that bind hydrophobic molecules and con¬tribute to tear viscosity. The lipid layer reduces evaporation from the aqueous layer and dysfunction may result in an evaporative dry eye state .
The aqueous layer is secreted by the main and accessory lacrimal glands and consists of water, electrolytes, dissolved mucins, and proteins. It has antibacterial properties due to the presence of IgA, lysozyme and lactoferrin, and it contains growth factors (EGF, TGF-a, HGF) secreted from the lacrimal gland in response to injury . It also contains leukocytes and pro-inflamma¬tory cytokines that accumulate when tear production is reduced during sleep. The aqueous phase can physically wash away debris and toxic agents that may cause inflammation. Deficiency of this layer results in an aqueous deficiency dry eye .
Mucins are at their highest concentration internally in the aqueous phase and they serve to increase viscosity and anchor the aqueous phase to the glyco- calyx of the external cells of the epithelium. Each mucin is a high-molecular- weight glycoprotein containing a protein core with radially linked carbohydrate side chains. The protein core forms the basis of further classification (e.g. MUC1, MUC2, etc.). Human mucins are classified according to anatomical distribution as transmembrane or secretory, and the secretory mucins are fur¬ther classified according to their physical properties as gel-forming or soluble. Secretory ocular mucins are principally produced by the conjunctival goblet cells (MUC5AC) but also by the lacrimal glands (MUC7). The glycocalyx of the superficial epithelial cells of the cornea and conjunctiva is formed of trans¬membrane mucins (MUC1, MUC2, and MUC4). MUC1 is essential to aid spreading of the secretory gel mucin produced by goblet cells and it also pre¬vents pathogens binding to the ocular surface . Damage to the mucus-binding complex will change the cell membrane from a hydrophilic to a hydrophobic surface and prevent normal tear film adherence. Loss of goblet cells and ocular surface mucus is a feature of cicatrising conjunctivitis, vitamin A deficiency, and chemical burns. Almost all of this complexity of structure is absent from artificial tears.
The initial management of dry eye disease relies on the use of artificial tear substitutes and the conservation of natural tears. Most artificial tears are lubricants with an electrolyte content that is only an approximation of normal tears. Viscosity agents are often added to artificial tears to increase the ocular surface residence time. An understanding of the complex interactions between aging, hormonal change, the environment, and the immune system has lead to new therapies to treat dry eye disease. Treatments that reduce associated conjunctival inflammation and stimulate the production of normal tear components may become increasingly important for the management of severe disease. An understanding of the behaviour of normal tears and the aetiology of dry eye is fundamental to the development of an effective treatment strategy.
Rational for Medical Management
Structure of the Tear Film
The tear film is part of a functional unit that comprises the tears, corneal and conjunctival epithelium, lacrimal glands, and lids. Disturbance of one or more of these interrelating structures can result in characteristic symptoms and signs of dry eye disease. This disease acts through the common disease mecha¬nisms of hyperosmolar tears and surface drying that damages the epithelial cells, with associated inflammation and a susceptibility to infection. The terms dry eye disease, dysfunctional tear syndrome, and keratoconjunctivitis sicca are synonymous.
Tears are mechanically spread over the ocular surface by upper lid blink¬ing, but the development of an effective tear film depends upon surfactant phospholipids in the surface layer and mucous in the basal layer that allows the fluid to adhere to the hydrophilic epithelial cells. The lubricating action of the tear film disperses the shearing forces on the epithelium caused by blinking. Finally, the tear film provides a smooth optical interface, transports metabo¬lites, and freely transmits oxygen and carbon dioxide to the cornea.
The structure of the tear film consists of an outer lipid layer lying on an aqueous layer that contains mucus. The meibomian glands secrete the lipid, which is released from the glands by lid movement. The lipid layer is composed of two phases: (1) an outer surface non-polar phase that contains waxes, choles¬terol esters, and triglycerides and (2) an inner polar aqueous-mucin phase that has surfactant properties. The inner polar phospholipids are bound to protein lipocalins within the aqueous layer that bind hydrophobic molecules and con¬tribute to tear viscosity. The lipid layer reduces evaporation from the aqueous layer and dysfunction may result in an evaporative dry eye state .
The aqueous layer is secreted by the main and accessory lacrimal glands and consists of water, electrolytes, dissolved mucins, and proteins. It has antibacterial properties due to the presence of IgA, lysozyme and lactoferrin, and it contains growth factors (EGF, TGF-a, HGF) secreted from the lacrimal gland in response to injury . It also contains leukocytes and pro-inflamma¬tory cytokines that accumulate when tear production is reduced during sleep. The aqueous phase can physically wash away debris and toxic agents that may cause inflammation. Deficiency of this layer results in an aqueous deficiency dry eye .
Mucins are at their highest concentration internally in the aqueous phase and they serve to increase viscosity and anchor the aqueous phase to the glyco- calyx of the external cells of the epithelium. Each mucin is a high-molecular- weight glycoprotein containing a protein core with radially linked carbohydrate side chains. The protein core forms the basis of further classification (e.g. MUC1, MUC2, etc.). Human mucins are classified according to anatomical distribution as transmembrane or secretory, and the secretory mucins are fur¬ther classified according to their physical properties as gel-forming or soluble. Secretory ocular mucins are principally produced by the conjunctival goblet cells (MUC5AC) but also by the lacrimal glands (MUC7). The glycocalyx of the superficial epithelial cells of the cornea and conjunctiva is formed of trans¬membrane mucins (MUC1, MUC2, and MUC4). MUC1 is essential to aid spreading of the secretory gel mucin produced by goblet cells and it also pre¬vents pathogens binding to the ocular surface . Damage to the mucus-binding complex will change the cell membrane from a hydrophilic to a hydrophobic surface and prevent normal tear film adherence. Loss of goblet cells and ocular surface mucus is a feature of cicatrising conjunctivitis, vitamin A deficiency, and chemical burns. Almost all of this complexity of structure is absent from artificial tears.
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