- Author: Mark Ventocilla, OD, FAAO; Chief Editor: John D Sheppard, Jr, MD, MMSc more...
The ocular surface may exhibit a wide variety of immunologic responses resulting in inflammation of the conjunctiva and cornea. In the Gell and Coombs classification system for various immunologic hypersensitivity reactions, 5 types of reactions are recognized. The major type I hypersensitivity reactions involving the conjunctiva are commonly referred to as allergic conjunctivitis and are further subclassified into seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC). Far less common are the more severe forms of allergic conjunctivitis, including atopic keratoconjunctivitis (AKC), giant papillary conjunctivitis (GPC), and limbal and tarsal vernal keratoconjunctivitis (VKC).
Diagnosis of allergic conjunctivitis is generally made by thorough history and careful clinical observation (see Clinical). The presence of an antigen triggers the allergic cascade, and, thus, avoidance of the offending antigen is the primary behavioral modification for all types of allergic conjunctivitis. In other respects, management of allergic conjunctivitis varies somewhat according to the specific subtype. Allergic conjunctivitis can be treated with a variety of drugs, including topical antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, and corticosteroids (see Treatment).
See the following for more information:
Immunologic reactions of conjunctiva and cornea
Type I (immediate) hypersensitivity reactions occur when a sensitized individual comes in contact with a specific antigen. Immunoglobulin E (IgE) has a strong affinity for mast cells, and the cross-linking of 2 adjacent IgE molecules by the antigen triggers mast cell degranulation.
The mast cell’s degranulation releases various preformed and newly formed mediators of the inflammatory cascade. Most notable of these inflammatory mediators are histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These various inflammatory mediators, together with various chemotactic factors, result in an increase in vascular permeability and migration of eosinophils and neutrophils. This type I hypersensitivity reaction is the most common allergic response of the eye. These immune-derived reactions may also be the underlying cause of more rare and serious ocular conditions, such as ocular cicatricial pemphigoid (OCP) and Mooren ulcer.
Type III hypersensitivity reactions result in antigen-antibody immune complexes, which deposit in tissues and cause inflammation. A classic systemic type III reaction is the Arthus reaction, and ocular type III hypersensitivity reactions include Stevens-Johnson syndrome and marginal infiltrates of the cornea. These type III reactions can often induce a corneal immune (Wessely) ring that disintegrates as the inflammatory reaction subsides.
Type IV hypersensitivity reactions, also known as cell-mediated immunity, are interceded by T lymphocytes. This inflammatory cell-driven reaction is also referred to as delayed-type hypersensitivity, since its onset is generally after 48 hours, in contrast to the type I reaction, which is an immediate hypersensitivity.
Type IV hypersensitivity reactions imply immunocompetence on the part of the individual since an intact immune system is required to mount the cell-mediated response. Ocular examples of type IV hypersensitivity include phlyctenular keratoconjunctivitis, corneal allograft rejection, contact dermatitis, and drug allergies.
Allergic conjunctivitis subtypes
Allergic conjunctivitis may be divided into 5 major subcategories.
Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are commonly grouped together.
Early diagnosis and treatment will help prevent the rare complications that can occur with this disease.
Since allergic conjunctivitis generally clears up readily, the prognosis is favorable. Complications are very rare, with secondary corneal ulcers or keratoconus occurring rarely. Although allergic conjunctivitis may commonly reoccur, it rarely causes any visual loss.
Patients should make every attempt to identify the allergen causing the problem and to avoid the offending antigen. For patient education information, see the Eye and Vision Center, as well as Pinkeye, Eye Allergies, and How to Instill Your Eyedrops.
Seasonal and perennial allergic conjunctivitis
Since the conjunctiva is a mucosal surface similar to the nasal mucosa, the same allergens that trigger allergic rhinitis may be involved in the pathogenesis of allergic conjunctivitis. Common airborne antigens, including pollen, grass, and weeds, may provoke the symptoms of acute allergic conjunctivitis, such as ocular itching, redness, burning, and tearing. The main distinction between SAC and PAC, as implied by the names, is the timing of symptoms.
Individuals with SAC typically have symptoms of acute allergic conjunctivitis for a defined period of time, that is, in spring, when the predominant airborne allergen is tree pollen; in summer, when the predominant allergen is grass pollen; or in fall, when the predominant allergen is weed pollen. Typically, persons with SAC are symptom-free during the winter months in cooler climates because of the decreased airborne transmission of these allergens. Seasonal allergic conjunctivitis can manifest itself through tear film instability and symptoms of eye discomfort during the pollen season. One study found that outside the pollen season, allergic inflammation did not cause permanent tear film instability.
In contrast, individuals with PAC may have symptoms that last the year round; thus, PAC may not be caused exclusively by seasonal allergens, although they may play a role. Other common household allergens, such as dust mite, cockroach dust, cigarette smoke, airborne allergens, molds, and pet dander, may be responsible for the symptoms of PAC.
VKC is a chronic bilateral inflammation of the conjunctiva, commonly associated with a personal and/or family history of atopy. More than 90% of patients with VKC exhibit one or more atopic conditions, such as asthma, eczema, or seasonal allergic rhinitis.
AKC is a bilateral inflammation of conjunctiva and eyelids, which has a strong association with atopic dermatitis. It is also a type I hypersensitivity disorder with many similarities to VKC, yet AKC is distinct in a number of ways.
In 1953, Hogan first described the association between atopic dermatitis and conjunctival inflammation. He reported 5 cases of conjunctival inflammation in male patients with atopic dermatitis. Atopic dermatitis is a common hereditary disorder that usually first appears childhood; symptoms may regress with advancing age. Approximately 3% of the population is afflicted with atopic dermatitis, and, of these, approximately 25% have ocular involvement.
Giant papillary conjunctivitis
GPC is an immune-mediated inflammatory disorder of the superior tarsal conjunctiva. As the name implies, the primary finding is the presence of "giant" papillae, which are typically greater than 0.3 mm in diameter.
A combination of type I and type IV hypersensitivity reactions may be responsible for the pathogenesis of GPC. It is believed that an antigen is present, in predisposed individuals, which stimulates the immunological reaction and the development of GPC.
Prolonged mechanical irritation to the superior tarsal conjunctiva, of the upper lid, from any of a variety of foreign bodies may also be a contributing factor in GPC. Although contact lenses (hard and soft) are the most common irritant, ocular prostheses, extruded scleral buckles, ocular prostheses, scleral shells, and exposed sutures following previous surgical intervention may also precipitate GPC.
Allergic conjunctivitis occurs very frequently and is seen most commonly in areas with high seasonal allergen and pollen counts. VKC occurs predominantly in areas with tropical and temperate climates, such as the Mediterranean, the Middle East, and Africa. The limbal form of VKC commonly occurs in dark-skinned individuals from Africa and India.
Sexual and age-related differences in incidence
VKC has a significant male preponderance, typically affecting young males. The onset of VKC generally occurs in the first decade and persists throughout the first 2 decades. Symptoms usually peak prior to the onset of puberty and then subside.
In general, the prognosis of SAC and PAC is good despite significant discomfort and undesirable cosmetic consequences. Occasionally, individuals with chronic recurrences develop significant conjunctivochalasis or, less commonly, a corneal Dellen secondary to persistent limbal conjunctival chemosis. Conversely, AKC and VKC may lead to significant corneal complications such as ulceration and opacification, leading to permanent visual loss. Lid involvement from any type of allergic conjunctivitis, particularly GPC, can significantly compromise contact lens tolerance. Medications used for allergic disease may lead to complications such as preservative toxicity and steroid-induced intraocular pressure (IOP) elevations or cataract.
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|Age at onset||Generally presents at a younger age than AKC' first decade||Second to third decade|
|Sex||Males are affected preferentially.||No sex predilection|
|Seasonal variation||Typically occurs during spring months||Generally perennial|
|Discharge||Thick mucoid discharge||Watery and clear discharge|
|Conjunctival scarring||Moderate incidence of conjunctival scarring||Higher incidence of conjunctival scarring|
|Horner-Trantas dots||Horner-Trantas dots and shield ulcers are commonly seen.||Presence of Horner-Trantas dots is rare.|
|Corneal neovascularization||Not present, unless secondary to infectious keratitis||Deep corneal neovascularization tends to develop|
|Presence of eosinophils in conjunctival scraping||Conjunctival scraping reveals eosinophils to a greater degree in VKC than in AKC||Presence of eosinophils is less likely|