the offending agent. Usually, the history provides the necessary clues, but sometimes a “rechallenge” is necessary to confirm a suspicion. Rechallenges should never be done in patients with a known systemic allergy to a drug.
Initial management of type I hypersensitivity reactions includes allergen avoidance or discontinuation. Adjunctive therapy may involve the use of cold compresses, artificial lubricants, topical antihistamines, mast-cell stabilizers, and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for pain. Topical vasoconstrictors, either alone or in combination with antihistamines, may provide acute symptomatic relief but should not be used long term.
Delayed hypersensitivity reactions are also treated with allergen withdrawal. In severe cases, a brief (several-day) course of mild topical corticosteroids or tacrolimus (Protopic) ointment 0.03% or 0.1% applied to the eyelids and periocular skin may speed resolution of eyelid and conjunctival inflammation.
Atopic Dermatitis
PATHOGENESIS Atopic dermatitis is a chronic condition in genetically susceptible individuals that usually begins in infancy or childhood and may or may not involve the external eye. The pathogenesis of atopic dermatitis involves a type IV hypersensitivity reaction, increased IgE hypersensitivity, increased histamine released from mast cells and basophils, and impaired cellmediated immunity.
CLINICAL PRESENTATION Diagnostic criteria for atopic dermatitis include pruritus, lesions on the eyelid and other sites (eg, joint flexures in adolescents and adults, face and extensor surfaces in infants and young children), and a personal or family history of other atopic disorders, such as asthma, allergic rhinitis, nasal polyps, and aspirin hypersensitivity. Other ocular findings include periorbital darkening, exaggerated eyelid folds, meibomianitis, ectropion, and chronic papillary conjunctivitis. The appearance of the skin lesions varies depending on the age of the patient. Infants typically have an erythematous rash, children tend to have eczematous dermatitis with secondary lichenification from scratching, and adults have scaly patches with thickened and wrinkled dry skin.
MANAGEMENT Allergens in the environment and in foods should be identified and minimized whenever possible. In general, the services of an allergist should be sought. Moisturizing lotions and petrolatum gels can be useful for skin hydration. Acute lesions can be controlled with a topical corticosteroid cream or ointment (clobetasone butyrate 0.05%), but long-term use of such medications is strongly discouraged to avoid skin thinning. Topical tacrolimus ointment 0.03% or 0.1% (Protopic) is also effective and has fewer side effects. Oral antipruritic agents such as antihistamines and mast-cell stabilizers can alleviate itching but may exacerbate dry eye with their anticholinergic activity.
Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. BMJ. 2005;330(7490):516.
Guglielmetti S, Dart JK, Calder V. Atopic keratoconjunctivitis and atopic dermatitis. Curr Opin Allergy Clin Immunol. 2010;10(5):478–485.
Immune-Mediated Disorders of the Conjunctiva
Hay Fever Conjunctivitis and Perennial Allergic Conjunctivitis
PATHOGENESIS Hay fever (seasonal) conjunctivitis and perennial allergic conjunctivitis are largely
IgE-mediated immediate hypersensitivity reactions. The allergen is typically airborne. It enters the tear film and comes into contact with conjunctival mast cells that bear allergen-specific IgE antibodies. Degranulation of mast cells releases histamine and a variety of other inflammatory mediators that promote vasodilation, edema, and recruitment of other inflammatory cells, such as eosinophils. In a presensitized individual, the activation and degranulation of mast cells can be triggered within minutes of allergen exposure.
CLINICAL PRESENTATION Patients with hay fever conjunctivitis often suffer from other atopic conditions, such as allergic rhinitis or asthma. Symptoms develop rapidly after exposure to the allergen and consist of itching, eyelid swelling, conjunctival hyperemia, chemosis, and mucoid discharge. Intense itching is a hallmark symptom. Attacks are usually short-lived and episodic. Contributing factors, including contact lenses and dry eye, should be identified, as these can play an important role in facilitating allergen contact with the ocular surface.
LABORATORY EVALUATION The diagnosis of hay fever conjunctivitis is generally made clinically. Conjunctival scrapings reveal the characteristic eosinophils, which are not normally present on the ocular surface (see Chapter 6). Challenge testing with a panel of allergens can be performed.
MANAGEMENT Efforts should first be directed at avoidance or abatement of allergen exposure. Thorough cleaning (or changing) of unclean or old carpets, linens, and bedding can be effective in removing accumulated allergens such as animal dander and house dust mites. Glasses or goggles can also serve as physical barriers. Treatment should be based on the severity of patient symptoms and includes one or more of the following:
Supportive
cold compresses artificial tears
Topical
topical antihistamines and mast-cell stabilizers topical NSAIDs
judicious, selective use of topical corticosteroids topical vasoconstrictors
Systemic
systemic antihistamines (may be effective for the short term but may be associated with increased dry eye)
Artificial tears are beneficial in diluting and flushing away allergens and other inflammatory mediators. Topical vasoconstrictors, alone or in combination with antihistamines, may provide acute symptom relief. However, their use for more than 5–7 consecutive days may predispose to compensatory chronic vascular dilation. Topical mast-cell stabilizing agents such as cromolyn sodium and lodoxamide tromethamine may be useful for treating seasonal allergic conjunctivitis. Treatment effects usually require continued use over 7 or more days; hence, these agents are generally ineffective in the acute phase of hay fever conjunctivitis. Topical cyclosporine and oral antihistamines may provide symptom relief in some patients. Hyposensitization injections (immunotherapy) can be beneficial if the offending allergen has been identified. Certain topical NSAIDs have been approved by the US Food and Drug Administration for use in ocular atopy, but their efficacy varies greatly. Reports of corneal perforations with the use of NSAIDs, especially the
generic forms, suggest the need for careful monitoring. Refills should be limited, and follow-up appointments need to be maintained. Topical corticosteroids are very effective in managing ocular allergy, but they should be used with caution, except in very severe cases, because of their toxicity. Topical tacrolimus can be used to treat the associated dermatitis.
Mantelli F, Lambiase A, Bonini S, Bonini S. Clinical trials in allergic conjunctivitis: a systematic review. Allergy. 2011;66(7):919– 924.
Mishra GP, Tamboli V, Jwala J, Mitra AK. Recent patents and emerging therapeutics in the treatment of allergic conjunctivitis.
Recent Pat Inflamm Allergy Drug Discov. 2011;5(1):26–36.
Ueta M, Kinoshita S. Ocular surface inflammation is regulated by innate immunity. Prog Retin Eye Res. 2012;31(6):551–575.
Vernal Keratoconjunctivitis
PATHOGENESIS Vernal (springtime) keratoconjunctivitis (VKC) is a seasonally recurring, bilateral inflammation of the cornea and conjunctiva that occurs predominantly in male children, who frequently, but not invariably, have a personal or family history of atopy. The disease may persist year-round in tropical climates. The immunopathogenesis appears to involve both types I and IV hypersensitivity reactions. The conjunctival inflammatory infiltrate in VKC consists of eosinophils, lymphocytes, plasma cells, and monocytes.
CLINICAL PRESENTATION Symptoms consist of itching, blepharospasm, photophobia, blurred vision, and copious mucoid discharge. Clinically, 2 forms of VKC may be seen: palpebral and limbal.
The inflammation in palpebral VKC is located predominantly on the palpebral conjunctiva, where a diffuse papillary hypertrophy develops, usually more prominently on the upper region. Bulbar conjunctival hyperemia and chemosis may also occur. In more severe cases, giant papillae resembling cobblestones may develop on the upper tarsus (Fig 7-3).
Figure 7-3 Palpebral vernal keratoconjunctivitis before (A) and after treatment (B) with tacrolimus. (Reproduced with permission
from Ohashi Y, Ebihara N, Fujishima H, et al. A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis. J Ocul Pharmacol Ther. 2010;26(2):165–174.)
Limbal VKC may develop alone or in association with palpebral VKC. It occurs predominantly in patients of African or Asian descent and is more prevalent in hotter climates. The limbus has a thickened, gelatinous appearance, with scattered opalescent mounds and vascular injection. HornerTrantas dots, whitish macroaggregates of degenerated eosinophils and epithelial cells, may be observed in the hypertrophied limbus of patients with limbal VKC (Fig 7-4).
Figure 7-4 Limbal vernal keratoconjunctivitis. Note the Horner-Trantas dots (arrow). (Courtesy of Charles S. Bouchard, MD.)
Several types of corneal changes associated with upper-tarsal lesions may also develop in VKC. Punctate epithelial erosions in the superior and central cornea are frequently observed. Pannus occurs most commonly in the superior cornea, but occasionally 360° corneal vascularization may develop. Noninfectious epithelial ulcers with an oval or shieldlike shape (the so-called shield ulcer) with underlying stromal opacification may develop in the superior or central cornea (Fig 7-5). An association between VKC and keratoconus has been reported. Stem cell deficiency may also occur in severe cases.
Figure 7-5 Shield ulcer in vernal keratoconjunctivitis. (Courtesy of James J. Reidy, MD.)
MANAGEMENT Therapy should be based on the severity of the patient’s symptoms and the ocular surface disease. Mild cases may be successfully managed with topical antihistamines. Climatotherapy, such as the use of home air-conditioning or relocation to a cooler environment, can be helpful. Patients with mild to moderate disease may respond to topical mast-cell stabilizers. In patients with seasonal exacerbations, these drops should be started at least 2 weeks before symptoms usually begin. Long-term maintenance dosing can be used for patients with year-round disease. Severe cases may require the use of topical corticosteroids or topical immunomodulatory agents such as cyclosporine or tacrolimus (see Fig 7-3). Both have been shown to be effective in reducing inflammation and