Introduction
Definitions
Dry eye occurs when there is inadequate tear volume or function, resulting in an unstable tear film and ocular surface disease. It is an extremely common condition, particularly in postmenopausal women and the elderly.
- •
Keratoconjunctivitis sicca (KCS) refers to any eye with some degree of dryness.
- •
Xerophthalmia describes a dry eye associated with vitamin A deficiency.
- •
Xerosis refers to the extreme ocular dryness and keratinization that occurs in eyes with severe conjunctival cicatrization.
- •
Sjögren syndrome is an autoimmune inflammatory disease of which dry eyes is a feature.
Physiology
Tear film constituents
The tear film has three layers ( Fig. 4.1 ):
- •
Lipid layer secreted by the meibomian glands.
- •
Aqueous layer secreted by the lacrimal glands.
- •
Mucous layer secreted principally by conjunctival goblet cells.
Spread of the tear film
The tear film is mechanically distributed over the ocular surface through a neuronally controlled blinking mechanism. Three factors are required for effective resurfacing of the tear film:
- •
Normal blink reflex.
- •
Contact between the external ocular surface and the eyelids.
- •
Normal corneal epithelium.
Lipid layer
- •
Composition
- ○
The outer lipid layer is composed of a polar phase containing phospholipids adjacent to the aqueous-mucin phase and a non-polar phase containing waxes, cholesterol esters and triglycerides.
- ○
The polar lipids are bound to lipocalins within the aqueous layer. These are small secreted proteins that have the ability to bind hydrophobic molecules and may also contribute to tear viscosity.
- ○
Lid movement during blinking is important in releasing lipids from glands. The thickness of the layer can be increased by forced blinking, and conversely reduced by infrequent blinking.
- ○
- •
Functions
- ○
To prevent evaporation of the aqueous layer and maintain tear film thickness.
- ○
To act as a surfactant allowing spread of the tear film.
- ○
Deficiency results in evaporative dry eye.
- ○
Aqueous layer
- •
Secretion
- ○
The main lacrimal glands produce about 95% of the aqueous component of tears and the accessory lacrimal glands of Krause and Wolfring produce the remainder.
- ○
Secretion of tears has basic (resting) and much greater reflex components. The latter occurs in response to corneal and conjunctival sensory stimulation, tear break-up and ocular inflammation, and is mediated via the fifth cranial nerve. It is reduced by topical anaesthesia and falls during sleep. Secretion can increase 500% in response to injury.
- ○
- •
Composition
- ○
Water, electrolytes, dissolved mucins and proteins.
- ○
Growth factors derived from the lacrimal gland, the production of which increases in response to injury.
- ○
Pro-inflammatory interleukin cytokines that accumulate during sleep when tear production is reduced.
- ○
- •
Functions
- ○
To provide atmospheric oxygen to the corneal epithelium.
- ○
Antibacterial activity due to proteins such as IgA, lysozyme and lactoferrin.
- ○
To wash away debris and noxious stimuli and facilitate the transport of leukocytes after injury.
- ○
To optically enhance the corneal surface by abolishing minute irregularities.
- ○
Mucous layer
- •
Composition
- ○
Mucins are high molecular weight glycoproteins that may be transmembrane or secretory in type.
- ○
Secretory mucins are further classified as gel-forming or soluble. They are produced mainly by conjunctival goblet cells but also by the lacrimal glands.
- ○
The superficial epithelial cells of the cornea and conjunctiva produce transmembrane mucins that form their glycocalyx (extracellular coating).
- ○
Staining of diseased epithelium with rose Bengal indicates that the transmembrane and gel mucous layers are absent and the cell surface exposed. Damage to the epithelial cells will prevent normal tear film adherence.
- ○
- •
Functions
- ○
To permit wetting by converting the corneal epithelium from a hydrophobic to a hydrophilic surface.
- ○
Lubrication.
- ○
Deficiency of the mucous layer may be a feature of both aqueous deficiency and evaporative states. Goblet cell loss occurs with cicatrizing conjunctivitis, vitamin A deficiency, chemical burns and toxicity from medications.
- ○
Regulation of tear film components
- •
Hormonal
- ○
Androgens are the prime hormones responsible for regulation of lipid production.
- ○
Oestrogens and progesterone receptors in the conjunctiva and the lacrimal glands are essential for the normal function of these tissues.
- ○
- •
Neural via fibres adjacent to the lacrimal glands and goblet cells that stimulate aqueous and mucus secretion.
Mechanism of disease
The four core inter-related mechanisms thought to be responsible for the manifestations of dry eye are tear instability, tear hyperosmolarity, inflammation and ocular surface damage. Inflammation in the conjunctiva and accessory glands as well as the ocular surface is present in 80% of patients with KCS and may be both a cause and consequence of dry eye, amplifying and perpetuating disease; the presence of inflammation is the rationale for specific anti-inflammatory measures such as steroid therapy.
Classification
The classification of dry eye usually applied is that of the 2007 International Dry Eye Workshop (DEWS), with a basic division into aqueous-deficient and evaporative types. Most individuals have considerable overlap between mechanisms, and it is important to be aware during patient assessment of the likely presence of multiple contributory factors.
Aqueous-deficient
- •
Sjögren syndrome dry eye (primary or secondary).
- •
Non-Sjögren syndrome dry eye.
- ○
Lacrimal deficiency: primary (e.g. age-related dry eye, congenital alacrima, familial dysautonomia) or secondary (e.g. inflammatory and neoplastic lacrimal gland infiltration, acquired immunodeficiency syndrome (AIDS), graft-versus-host disease, lacrimal gland or nerve ablation).
- ○
Lacrimal gland duct obstruction, e.g. trachoma, cicatricial pemphigoid, chemical injury, Stevens–Johnson syndrome.
- ○
Reflex hyposecretion: sensory (e.g. contact lens wear, diabetes, refractive surgery, neurotrophic keratitis) or motor block (e.g. seventh cranial nerve damage, systemic drugs).
- ○
Evaporative
- •
Intrinsic
- ○
Meibomian gland deficiency, e.g. posterior blepharitis, rosacea.
- ○
Disorders of lid aperture, e.g. excessive scleral show, lid retraction, proptosis, facial nerve palsy.
- ○
Low blink rate, e.g. Parkinson disease, prolonged computer monitor use, reading, watching television.
- ○
Drug action, e.g. antihistamines, beta-blockers, antispasmodics, diuretics.
- ○
- •
Extrinsic
- ○
Vitamin A deficiency.
- ○
Topical drugs including the effect of preservatives.
- ○
Contact lens wear.
- ○
Ocular surface disease such as allergic conjunctivitis.
- ○
Effect of environmental factors
As well as the basic classification, DEWS draws attention to the effect of the environment on the type of dry eye with which a patient presents. These can be both internal, such as age, hormonal status and behaviour patterns, and external, such as the exacerbation of evaporative factors in an atmosphere with low relative humidity.
Sjögren Syndrome
Sjögren syndrome (SS) is an autoimmune disorder characterized by lymphocytic inflammation and destruction of lacrimal and salivary glands ( Fig. 4.2A ) and other exocrine organs. The classic clinical triad consists of dry eyes, dry mouth ( Fig. 4.2B ) and parotid gland enlargement ( Fig. 4.2C ), but other features are common and can affect all organ systems. The condition is classified as primary when it exists in isolation, and secondary when associated with another disease, commonly rheumatoid arthritis or systemic lupus erythematosus. Primary SS affects females more frequently than males. Although in clinical practice the diagnosis may be made on less stringent grounds, the American College of Rheumatology (ACR) criteria for diagnosis specify, in patients with a clinical picture suggestive of SS:
- •
Positivity for anti-SSA or anti-SSB antibodies, or positive rheumatoid factor together with significantly positive antinuclear antibody.
- •
Ocular surface staining above a certain grade.
- •
Focal lymphocytic sialadenitis to a specified extent on salivary gland biopsy (see Fig. 4.2A ).
Treatment options for SS include a range of symptomatic treatments for dry eye, as discussed below, dry mouth and other manifestations, salivary stimulants (e.g. oral pilocarpine) and in some cases immunosuppression and biological blockers such as rituximab.
Clinical Features
Symptoms
The most common ocular symptoms are feelings of dryness, grittiness and burning that characteristically worsen over the course of the day. Stringy discharge, transient blurring of vision, redness and crusting of the lids are also common. Lack of emotional or reflex tearing is unusual. The symptoms of KCS are frequently exacerbated on exposure to conditions associated with increased tear evaporation (e.g. air-conditioning, wind and central heating) or prolonged reading or video display unit use, when blink frequency is reduced.
Signs
- •
Posterior (seborrhoeic) blepharitis with meibomian gland dysfunction is often present ( Figs 4.3A and B ).
