Spring is in the air. But, the spring air is full of pollen, mold and other sources of allergenic proteinsnot a good thing for allergy sufferers.

The eye is essentially an open window that encounters a multitude of environmental substances, making it a prime site for allergic inflammation. Here, we will discuss the pathophysiology of ocular allergies and the four common manifestations.

Atopic keratoconjunctivitis is a type I ocular hypersensitivity reaction. Note the thickened eyelid margins and scaly, swollen lids.

Pathophysiology
Ocular allergic disease results from a hypersensitive reaction that starts when an allergen becomes trapped in the tear film. Antigen presenting cells (APCs), which are located in the conjunctiva and the epithelial and subepithelial layers of the body, engulf the allergen, then migrate to a draining lymph node and deliver the allergen to CD4+ helper T cells. These cells then proliferate and become T helper type 2 (Th2) cells.

Next, the Th2 cells produce interleukin-4 (IL-4) and -13 (IL-13). These two cytokines cause B cell lymphocytes to produce immunoglobulin E (IgE), the antibody thats associated with allergy.^1-4 (In non-allergic individuals, Th1 cells produce the cytokine interferon- gamma, which blocks the IgE production induced by IL-4 and IL-13.^1,5,6)

The IgE then binds to the surface of the conjunctival mast cells, which store histamine in cytoplasmic granules. The mast cells degranulate, and the explosive release of histamine causes the immediate or early phase of an allergic reaction. (Eosinophils are not present in type I hypersensitivity acute phase reactions.)

Once released, histamine binds to receptors on vascular smooth
muscle, causing vasodilation (hyperemia, redness) and the formation of gaps between endothelial cells, resulting in vascular permeability. Fluid leaks out of the vessels into tissue (chemosis, tearing, lid swelling, rhinorrhea). Histamine binds to receptors on nerve endings, leading to pruritus (itching), the hallmarks of ocular allergy.^1,4-6

Persistent signs and symptoms comprise a late-phase response, resulting from mediators released by the other cells, such as eosinophils. Eosinophils release major basic protein, a toxic product resulting in keratitis and shield ulcers associated with chronic allergic conditions.⁵

A Type 1 allergic reaction (allergic conjunctivitis).

A Type IV allergic reaction (contact dermatitis).

By being aware of the cellular and molecular basis of the allergic response and the common manifestations of ocular allergy, we can enable our allergic patients to explore, rather than deplore, this season of rebirth.

The Common Manifestations of Ocular Allergy Seasonal and Perennial Allergic Conjunctivitis (SAC, PAC) A severe conjunctival swelling (chemosis) resulting from an allergen in the conjunctiva. Type of Hypersensitivity Reaction: Type I. Cause(s): SAC is triggered by pollens. PAC is triggered by dust mite feces and animal dander.5,8,9 Prevalence: Both conditions are found in up to 98% of patients who have ocular allergies.9 Symptoms: A red, itchy and watery eye. Signs: Conjunctival chemosis and lid swelling. Rhinitis is an associated finding.5 Treatment: A combination antihistamine-mast cell stabilizer, cold compresses, tear substitutes to flush the allergen, and avoidance of the allergen. Topical corticosteroids are considered in severe or recalcitrant cases, but they should only be used for a short time given the potential side effects of cataract and increased intraocular pressure. However, Alrex, (loteprednol etabonate 0.2%, Bausch & Lomb) has been found to be safe for long-term use.10 Vernal Keratoconjunctivitis (VKC) Giant papillae seen on the upper tarsal conjunctivaa hallmark sign of VKC. Type of Hypersensitivity Reaction: Type I and type IV. Cause(s): Climate, sensitivity to individual-based allergen and genetic predisposition. Prevalence: Males younger than 10 years of age, especially those who live in warm climates and who have a family history of atopic disease.8,11 VKC usually decreases with puberty.5,8,12 Symptoms: Intense itching, foreign-body sensation, photophobia, tearing and stringy mucoid discharge. Signs: Papillae on the palpebral conjunctiva and possible limbal involvement with Trantas dots. Corneal involvement frequently occurs with the limbal form, but is more commonly associated with the palepbral form.5 Corneal involvement can lead to scarring and decreased visual acuity.5,8,11 Treatment: The same agents used to treat allergic conjunctivitis. Topical corticosteroids may also be warranted. Limited studies have reported the use of cyclosporine for VKC.5 Also, research is being done on adhesion molecule inhibitors to prevent eosinophil recruitment.6 A promising approach targets chemokine antagonismeotaxin 1 or chemokine receptor-3 (CCR3)to inhibit mast cell and eosinophil activity.9,13 Atopic Keratoconjunctivitis (AKC) Type of Hypersensitivity Reaction: Type I. Cause(s): Any type of seasonal allergen. Prevalence: Males ages 30 to 50, who have a history of atopic dermatitis or eczema since childhood and a family history of atopy, with its triad of hay fever, asthma and eczema. The ocular findings of AKC manifest later in life.5 Symptoms: Severe itching of the conjunctiva, lid skin and periorbital area. Signs: Atopic blepharitis with thickened eyelid margins and scaly, swollen lids; conjunctival hyperemia; chemosis; palpebral papillae; and gelatinous limbal nodules. Corneal lesions range in severity from punctate keratitis to micropannus and infectious and noninfectious shield ulcers.5,8,11,13 Cataracts and keratoconus are occasional findings.5 Treatment: The same agents used to treat allergic conjunctivitis and VKC. Topical corticosteroids may also be warranted. The molecule CD14 may be a potential target for preventing atopic disease.14 Allergic and Irritant Contact Dermatitis (ACD, ICD) of the Eyelid Type of Hypersensitivity: Type IV. The allergen acts as a hapten that must bind to an epidermal protein to trigger an immune reaction.5 Cause(s): Atropine, neomycin, skin/hair products, poison ivy exposure and preservatives (e.g., benzalkonium chloride and thimerosal) all can trigger ACD. Physical, mechanical or chemical irritants, such as detergents and solvents trigger ICD. A direct toxic effect (dose- and potency-dependent) incites the inflammatory response; sensitization is not required. Onset varies from minutes or hours to weeks after exposure. Prevalence: ACD occurs more frequently in women than in men. This is mostly the result of a nickel allergy, which in most countries occurs much more commonly in women than in men.15 ICD is common in patients whose occupations involve repeated hand washing or repeated exposure of the skin to water, food materials and other irritants.16 Symptoms: The development of dermatitis.15 Itching is an important feature in ACD.5,13 Pain and burning exceeds itching in the acute stage of ICD. Signs: Erythema, vesicle formation, edema, scaling and weeping lesions. A papillary conjunctivitis may be seen in both forms of contact dermatitis. Treatment: Avoidance of the inciting agent, short-term use of topical steroids and cool compresses for both conditions. J.W.

Dr. Wing is an associate professor at the Pennsylvania College of Optometry in Elkins Park, Pa.

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