Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008

Mast cell stabilizers include cromolyn sodium 4% (Opticrom, Crolom) and lodoxamide tromethamine 0.1% (Alomide), which are currently approved by the U.S. Food and Drug Administration for VKC but offer offlabel relief for allergic conjunctivitis. Other mast cell stabilizers include pemirolast (Alamast) and nedocromil sodium 2% (Alocril), with both approved for treatment of itching in allergic conjunctivitis. Perennial allergic conjunctivitis may be treated with mast cell stabilizers year round.

Drugs that have both a mast cell stabilizing effect and act as an antihistamine include olopatadine hydrochloride 0.1% (Patanol), olopatadine hydrochloride 0.2% (Pataday), ketotifen fumarate 0.5% (Zaditor), azelastine hydrochloride 0.05% (Optivar), and epinastine hydrochloride 0.05% (Elestat).These drugs are dual-acting and also multiacting drugs. Ketotifen (Zaditor) and azelastine hydrochloride (Optivar) also decrease chemotaxis and eosinophil activation. Epinastine, in addition to being a selective H1 receptor inhibitor, has an affinity for other receptors, including the H2 receptor.This group of drugs provides both long-term management for allergic conjunctivitis and rapid relief of symptoms. Ophthalmic olopatadine 0.2% has also been found to be effective in decreasing nasal symptoms that include sneezing and itchy and runny nose.These drugs may be used in patients 3 years of age and older. Dosage is twice a day, except for olopatadine 0.2%, which is a once a day dosage.

The use of steroids should be reserved for severe cases of allergic conjunctivitis, and long-term use should be limited because of their potential adverse effects. Loteprednol is a site-active steroid with a good safety profile and less potential for steroid side effects. It therefore is a good treatment option for seasonal allergic conjunctivitis. Site-active (or specific) drugs, such as loteprednol, undergo a rapid transformation to an inactive metabolite when they enter the target areas, therefore decreasing the potential for the side effects seen with traditional steroids. Loteprednol is formulated as a 0.2% suspension (Alrex) and a 0.5% suspension (Lotemax). Loteprednol 0.2% has been found to be effective in treating seasonal allergic conjunctivitis and a safe option for long-term treatment of seasonal and perennial allergic conjunctivitis.When steroid treatment is used to alleviate acute symptoms, long-term management includes the use of antihistamines, decongestants, or mast cell stabilizers to ultimately replace the steroid.

Oral antihistamines may be used to alleviate symptoms of allergic rhinoconjunctivitis. These include over- the-counter first-generation antihistamines such as chlorpheniramine maleate (Chlor-Trimeton) and diphenhydramine hydrochloride (Benadryl). Second-generation less sedating antihistamines include fexofenadine hydrochloride (Allegra), loratadine (Claritin), desloratadine (Clarinex), and cetirizine hydrochloride (Zyrtec). Dry eye symptoms may be an adverse reaction to oral antihistamines, including second generation.

Combination therapy of topical and systemic drugs is also an important treatment consideration. When symptoms are isolated to the eye, topical treatment is rapid and most efficient. However, in cases of rhinoconjunctivitis, when nasal symptoms are also present, optimum management includes combining topical ophthalmic medications, olopatadine or ketotifen, for example, with a nasal spray or systemic treatment, such as the oral antihistamine desloratadine. For rhinitis, nasal steroids provide a good treatment option. The above approach targets particular areas of involvement by utilizing the most efficacious route of treatment.

Treatment for allergic rhinitis may also include standard allergen immunotherapy that requires multiple injections.The short-term benefit is limited and the longterm effect is finite. Clinical trials have found promising results for the Amb a 1-immunostimulatory oligodeoxyribonucleotide conjugate (AIC) vaccine in those individuals allergic to ragweed. A series of six injections over 6 weeks has been found to provide improvement in rhinoconjunctivitis, with encouraging results for long-term effect.

Other treatment options include the use of topical NSAIDs, which provide relief of itching. Ketorolac tromethamine (Acular) is the only NSAID approved for the treatment of seasonal allergic conjunctivitis, with symptomatic relief occurring within 30 minutes after administration.Topical NSAIDs are not typically the treatment option chosen, because the other classes of drugs provide better well-established relief.

Giant Papillary Conjunctivitis

GPC is an inflammatory condition that occurs primarily in contact lens wearers. The clinical manifestations include giant papillae in the upper tarsal conjunctiva, increased mucous secretion, itching, and lens intolerance. When GPC occurs with contact lens wear, it is referred to as contact lens papillary conjunctivitis (CLPC). In addition to contact lens wearers, GPC may also affect patients with ocular prostheses or exposed sutures.

All ages and both genders may be affected. Although study results vary widely, 3% to 15% of rigid lenses wearers and 5% to 10% of soft contact lens wearers are reported to develop GPC. Eighty-five percent of GPC occurs in hydrogel lens wearers.The incidence of GPC is lower in those wearing disposable versus conventional contact lenses and is lower with more frequent versus less frequent lens replacement.

Etiology

The cause of GPC is multifactorial,with mechanical trauma and hypersensitivity reactions involved. In those genetically predisposed, the antigen-coated contact lens may trigger the hypersensitivity reaction, which includes both an immediate type I reaction and a type IV delayed reaction.

The mechanical and immunologic mechanisms, although distinct, overlap in the pathogenesis of GPC.

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With each blink the antigen-coated contact lens mechanically traumatizes the tarsal conjunctiva. This process causes the release of mediators, such as neutrophil chemotactic factor and eosinophil chemotactic factor, which attract inflammatory cells (e.g., neutrophils, eosinophils, mast cells, and basophils). The immunologic sequence of events results in an increase in tear immunoglobulins IgE and IgG and C3 anaphylatoxin. The tear immunoglobulins and C3 anaphylatoxin then interact with the inflammatory cells produced from the mechanical trauma. This interaction causes the release of vasoactive amines, resulting in subsequent clinical manifestations. Papillae formation is related to structural changes in the conjunctival epithelium and stroma associated with increased eosinophils and inflammatory cells.

A variety of factors contributes to the development of GPC: contact lens coating, increased wearing time and

therefore greater antigen exposure, infrequent lens replacement, individual reaction to the lens type, larger lens and therefore a greater area for antigenic deposits, and a genetic predisposition. Any type of contact lens may cause GPC, including high Dk silicone lenses. Meibomian gland dysfunction has been suggested to be a factor in GPC; however, findings are inconsistent. A history of environmental allergies may be a predisposing factor,with GPC found more commonly in patients with these allergies.

Diagnosis

The diagnosis of GPC is based on the clinical presentation and a history of contact lens wear, ocular prothesis, or exposed sutures. In 90% of cases both eyes are affected. Symptoms may occur after only weeks of contact lens wear or may manifest after many years of wear. Four clinical stages of GPC have been described.Table 27-4 delineates these various stages.

Conjunctival papillary changes are an integral component of GPC. Micropapillae, by definition, are smaller than 0.3 mm and are present in 80% of normal eyes. Macropapillae are 0.3 to 1.0 mm in size and are usually not a normal clinical presentation. Giant papillae are at least 1 mm in size and develop, separate from normal papillae, as part of the pathologic process of GPC.

Soft contact lens wearers first show papillary changes in the upper or inside edge of the tarsal plate (zone 1), followed by involvement of the middle area of the tarsal plate (zone 2), and finally progression toward the lid margin (zone 3). Rigid contact lens patients have fewer and smaller papillae that appear closer to the lid margin (zone 3) or in the central zone (zone 2) of the upper tarsal area (Figure 27-2).

There are two types of papillary presentations of CLPC: general and local. General CLPC may affect two, more, or all lid zones (Figure 27-3). Localized CLPC affects one or two lid zones, reflecting a mechanical trauma (Figure 27-4). General CLPC is more commonly seen with low Dk hydrogel lenses, and local CLPC is more commonly seen with high Dk silicone lenses. With silicone hydrogel lenses typically zones 2 and 3 are involved. The stiffer lens material of silicone lenses and the lens edge are probable factors. Localized papillary changes are also seen with ocular prosthetics and exposed sutures. Although symptoms are similar between both general and local CLPC, the occurrence of symptoms is greater in the general form. An exception is dryness, which is more common to local type CLPC.

GPC develops earlier in patients wearing soft contact lenses than in those wearing rigid lenses. The reaction has been found to develop as early as 3 weeks after initiation of soft contact lens wear and may begin as early as 14 months after initiation of rigid lens wear. The average time for GPC to develop with soft lens wear is 10 months; however, the interval varies depending on the study.

Figure 27-3 Generalized giant papillary conjunctivitis.

The differential diagnosis of GPC includes VKC, which also presents with giant papillae. In contrast to VKC, GPC has a history of contact lens wear, both genders are affected,all ages are affected,a milder amount of itching is present, and it occurs without seasonal predisposition.

Management

The management of GPC depends on the severity of symptoms. Management includes frequent lens replacement or disposable contact lenses, appropriate contact lens cleaning, and vigilant monitoring of contact lens wearing time. Medical management includes use of mast cell stabilizers, topical NSAIDs, and steroids.

Frequent or planned and daily replacement lenses play an important role in the management of GPC. The incidence of GPC is significantly decreased when lenses are replaced in less than 4 weeks (36% incidence with 4 weeks or longer lens replacement vs. 4.5% incidence with daily to every 3 week lens replacement). In those at risk, replacement should be no longer than 2 weeks, and in

Figure 27-2 Delineation of the upper lid zones. (Reprinted with permission Optom Vis Sci 2006;83:30.)

Figure 27-4 Localized giant papillary conjunctivitis.(Reprinted with permission Optom Vis Sci 2006;83:31.)

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those with a predisposing history of allergy, more frequent lens replacement is warranted.

In addition, assessment of the patient’s contact lens cleaning regimen is also important. Cleaning regimen,once a critical component to lens care,has been eliminated with daily disposable lens replacement and has evolved with frequent lens replacement. Daily cleaning is essential, and when applicable, disinfection with a hydrogen peroxide system may still be an important consideration.The use of enzymatic cleaning has diminished because disposable lenses have replaced the need for it, but it may be a consideration in select cases.

Contact lens wearing time should be decreased, and in some cases contact lens wear should be discontinued. Discontinuing contact lens wear often relieves the symptoms within 2 to 3 days. Lens wear should not be resumed until mucous discharge, redness, and irritation are cleared. Discontinuing contact lens wear for 3 weeks or longer provides the best success in managing GPC patients.

In patients who present with early symptoms of GPC, replacing the old contact lenses with new lenses has a 78% rate of success.When more advanced GPC is present, however, discontinuing contact lens wear and then refitting the patient provides the best results, with success achieved in 93.96%.

Lens material and replacement schedule are important management considerations. When contact lenses are replaced frequently, the antigenic load is decreased, and the subsequent mechanism that leads to GPC is less likely to develop.The suggested treatment plan for the various stages of GPC is delineated in Table 27-4.

Pharmacologic treatment of GPC is used in patients with moderate to severe clinical manifestations. Treatment options include mast cell stabilizers, NSAIDs, and steroids (see Table 27-1).

Mast cell stabilizers are best used for long-term control of clinical manifestations. Although contact lens wear is not suggested with use of mast cell stabilizers, drops may be instilled before lens insertion and after lens removal and as directed according to practitioner’s discretion during lens wear.With prolonged use,a maintenance dose of twice a day may be prescribed.

Although not a common treatment option, NSAIDs may be effective for GPC. NSAIDs may improve the signs and symptoms of GPC in 2 to 4 weeks of treatment.

Steroids may also be used in the treatment of GPC, with careful monitoring for adverse effects. Loteprednol 0.5% is an effective and safe treatment option for GPC when used four times a day. Improvement in itching, lens tolerance, and papillae has been noted after 1 week of therapy and continued for 6 weeks after treatment.When intraocular pressure does rise with loteprednol use, it is usually transient, and pressure typically returns to normal within 7 days of drug discontinuation.

With appropriate management patients with GPC may continue contact lens wear. Even with good control of the

inflammation associated with GPC, papillary changes may remain or papillae may decrease slowly in size.

Vernal Keratoconjunctivitis

VKC is an uncommon, bilateral, ocular allergic disorder. More frequently it affects children.Vernal means “spring,” and VKC typically occurs during the months of April to August; however, it may occur anytime during the year. In 23% of patients clinical manifestations occur continuously. In more than 60% recurrences occur. VKC is more likely to affect those living in warm dry climates.

Adolescent boys are affected twice as often as girls. After puberty, however, girls are increasingly afflicted. After the age of 20 years women and men are affected equally, which may reflect a hormonal influence.The age at onset for VKC is usually before puberty and reaches a peak at around 11 to 13 years. Patients as young as

1 month and as old as 75 years may be affected; 80% of VKC patients are younger than 14 years.

VKC is a self-limited disease, with a duration ranging from 1 to 23 years, with a median of about 5 years. VKC usually runs its course by the time patients reach their early twenties, with the severity of the disease decreasing between 16 and 21 years of age. Some VKC patients develop an overlying AKC.Typically, the patient or family has a history of atopic disease, such as asthma, eczema, or allergic rhinitis.

VKC may present as a palpebral disease, limbal disease, or mixed disease that has both limbal and palpebral manifestations. Palpebral or mixed disease has the most serious sequelae, which include corneal scarring and vision loss.

Etiology

The pathophysiology of VKC is derived from a combination of type I and IV hypersensitivity reactions.This allergic response involves IgE,Th-2 lymphocytes, eosinophils, mast cells, basophils, neutrophils, macrophages, proinflammatory cytokines, interleukins, histamine, and other associated mediators. Also involved in this immune response are hormonal and neuroendocrine influences. This immune response results in the clinical manifestations of photophobia, itching, redness, tearing, papillae, corneal vascularization, mucous discharge, and plaque formation.

Specifically, the giant papillae found in VKC consist of dense fibrous tissue (connective tissue hyperplasia) as well as eosinophils, mast cells, basophils, polymorphonuclear leukocytes, lymphocytes, and macrophages. Mucous discharge contains eosinophils. Trantas’ dots, which appear as elevated white opacities at the limbus, contain eosinophils and epithelial cells.

The cause for corneal changes is multifactorial. These include a mechanical component, from the giant palpebral papillae; conjunctival inflammation; inflammatory toxins; and an ocular surface component (i.e., dry eyes).

Mediators released from mast cells and eosinophils also play a role in corneal changes.

There is also evidence of autonomic involvement in VKC. Muscarinic and β1-adrenergic receptors are altered in the inflamed conjunctiva. Also, muscarinic receptor stimulation activates the goblet cells to produce mucus.

Diagnosis

Diagnosis of VKC is based on clinical presentation, the young age at onset, and geographic distributions. VKC is typically a bilateral disease, and the patient presents with ocular symptoms that include intense itching, tearing, pain or foreign body sensation, blurred vision, and mucous discharge. Signs include giant papillae on the upper tarsal conjunctiva or limbus, corneal changes that range from superficial keratopathy to shield ulcer, and Trantas’ dots.

An early stage of VKC, known as forme fruste, should also be considered when making the diagnosis. Here the patient experiences severe itching, mucous discharge, and matting of the eyelids in the morning. Giant papillae have not yet formed on the upper palpebral conjunctiva, which distinguishes forme fruste from the more advanced stages of VKC.

Palpebral VKC is characterized by conjunctival and corneal changes. Although conjunctival papillae may be found on the lower palpebral conjunctiva, the classic presentation in VKC is giant papillae greater than or equal to 1 mm on the upper tarsal conjunctiva (Figure 27-5). These cobblestone papillae may be flat topped, with the tips eroded, which results in fluorescein staining. The papillae may cause a mechanical ptosis. Larger papillae correlate with a poorer prognosis and potential for chronicity.

The corneal response in VKC occurs with varying levels of severity. The changes initially begin with punctate epithelial keratopathy, which may be serious enough to cause a decrease in vision to 20/200, with associated photophobia. Corneal epithelial macroerosion or areas

Figure 27-5 Papillary changes in vernal conjunctivitis.

Figure 27-6 Shield ulcer in vernal conjunctivitis.

without epithelium may develop. Mucus may adhere to the areas of disrupted epithelium. Plaque formation, along with mucous and fibrin deposition, occurs on the area of macroerosion. Other corneal changes include pannus or neovascularization; keratitis, usually of the superior cornea; keratitis with small gray-white intraepithelial opacities (keratitis epithelialis vernalis of Tobgy); shield ulcers (Figure 27-6); and scarring. Decreased vision secondary to corneal scarring affects 6%.

Limbal VKC is characterized by limbal papillae or nodules that are small, semitransparent, gray-white to pink, gelatinous elevations at the limbal–corneal junction. These limbal papillae are analogous to the tarsal papillae found in palpebral VKC. Limbal VKC does not typically have giant papillae or corneal plaque formations. Complications from corneal disease are usually absent in limbal disease, perhaps because there is less inflammatory activity. Limbal VKC has a shorter clinical course than palpebral VKC. Individuals affected by limbal disease are also less likely to suffer from other atopic diseases.

Trantas’ dots may be found in any of the types of VKC (Figure 27-7).They are usually found at the upper limbus

Figure 27-7 Patient with Trantas’ dots in vernal keratoconjunctivitis.

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but may also be found on the bulbar conjunctiva, semilunar folds, or less commonly on the tarsal conjunctiva. They occur either singly or in groups, as grayish white to white-yellow dots, and occur in approximately 69% of patients with mixed VKC, 41% of patients with limbal VKC, and 21% of those with palpebral VKC.Trantas’ dots last for several days to up to a week.

Other clinical manifestations of VKC include conjunctival scarring, with possible symblepharon formation, and high corneal astigmatism and keratoconus. Dennie’s line, an extra lid fold, may be seen. Cataracts may also occur.

VKC is differentiated from GPC and AKC by its clinical presentation. Distinguishing features include age at onset, male predisposition, geographic distribution, lack of relationship to contact lens use, and absence of atopic dermatitis.

Management

Treatment of VKC depends on the severity of symptoms and the clinical presentation. In mild cases the use of cool compresses, ocular lubricants, decongestant– antihistamine combinations, and mast cell stabilizers may be sufficient. Environmental controls include maintaining a cool moist environment, for example, with air conditioning.

In moderate to severe cases topical and oral antihistamines, mast cell stabilizers, NSAIDs, and topical steroids are treatment options. Acetylcysteine may also be used four times a day for the elimination of mucus.Topical antihistamines such as emedastine are good treatment options. These agents are effective and well tolerated in treating VKC,with improvement in symptoms seen generally within 1 to 2 weeks.

Mast cell stabilizers play an important role in the management of VKC. In addition to its mast cell stabilizing effect, lodoxamide, specifically, has been found to have other actions. These actions include decreasing levels of Th-2 in the tears, inhibiting the release of cytokines from the mast cells and thus affecting papillary formation,and interrupting the recruitment of eosinophils after mast cell degranulation and therefore diminishing the opportunity for corneal changes, mucous secretion, and the formation of Trantas’ dots.

Treatment with mast cell stabilizers is most effective when begun before the onset of symptoms, because 14 days may be needed for clinical effects to occur. The dosage may be continued during the peak season. Lodoxamide has been found to be effective in treating serious corneal complications in VKC and in improving papillae, limbal involvement (papillae, hyperemia, and Trantas’ dots), and conjunctival discharge. Lodoxamide has been found to be superior to cromolyn sodium 4% in alleviating the signs and symptoms of VKC.

Because clinical improvement may be delayed with mast cell stabilizers, a topical antihistamine or steroid may

be used concomitantly to alleviate symptoms immediately. Dual-acting drugs, with mast cell stabilizing and antihistamine effects, may also be used. Olopatadine 0.1% has been found to be effective in treating the clinical manifestations of VKC, including decreasing mucous discharge by decreasing the number of goblet cells. NSAIDs, such as diclofenac, alleviate symptoms, probably through the decreased production of prostaglandins. In very severe cases oral steroids may be considered.

Topical steroids are a mainstay of treatment, with up to 85% of patients requiring its use. Dosage for topical steroid treatment is adjusted depending on the severity of the clinical presentation. Prednisolone 1% (acetate or phosphate) may be used during the first few days, with the dosage tapered over 1 to 2 weeks. Maintenance therapy includes a reduced dosage of one to three times per day or the use of less potent steroids, such as fluorometholone or loteprednol 0.2%. Pulse therapy is also a treatment option and sometimes alleviates acute symptoms. This approach may be used in conjunction with a mast cell stabilizer for long-term management. In pulse therapy prednisolone 1% may be used every 1 to 2 hours while awake for 4 to 7 days and then four times a day for 4 to 7 days.

Intractable cases of VKC may be effectively treated with a combination of systemic aspirin and topical cromolyn sodium. Aspirin inhibits cyclooxygenase and the production of prostaglandins from mast cells in VKC.Aspirin used in conjunction with the mast cell stabilizers results in improvement of both clinical signs and symptoms.

Topical cyclosporine A is an effective,safe,well-tolerated treatment option for severe or intractable VKC. An immunosuppressant, it affects and inhibits cell-mediated and immediate hypersensitivity reactions. It inhibits the release of interleukins, and it may prevent mediator release from mast cells. Relief is often noted after the first month of cyclosporine treatment, with continued results for up to 2 years. Some, however, have found a return of signs and symptoms 1 to 2 months after discontinuance of treatment.

Shield ulcers may be treated with topical cyclosporine A. Steroids in conjunction with a topical antibiotic and cycloplegic are also used in the treatment of shield ulcer.

In severe refractory cases of VKC, treatment options include surgical excision of the giant papillae and cryotherapy of the upper tarsus. Improvement is limited, however, and scarring may result. Supratarsal steroid injection is another treatment option. Symptomatic relief takes place in 1 to 5 days, giant papillae decrease in 5 to 17 days, and shield ulcers resolve in 12 to 20 days. After injection, patients are maintained on conventional treatment modalities. Mitomycin C, which inhibits inflammatory cells and fibroblast proliferation, has been found to alleviate the signs and symptoms of severe refractory cases. Amniotic membranes are another treatment consideration for severe cases.

Atopic Keratoconjunctivitis

AKC is one of the most serious of the ocular allergies because of the potential for loss of vision from corneal involvement. Patients with AKC usually have a personal or family history of atopic disease such as asthma, hay fever, and urticaria. Atopic dermatitis has ocular involvement in 25% to 40% of cases.

AKC may occur throughout the year, with no seasonal, geographic, or climatic preference. Men are more commonly affected. With age at onset in late teens or early twenties,AKC is typically an adult disease, affecting those aged 30 to 50 years. A patient may subsequently be afflicted with AKC for decades.

Etiology

AKC is believed to be a result of both a type I (IgE) and type IV (T cell–mediated) hypersensitivity reaction.

Patients with AKC may have a depressed T-cell function. Elevated levels of serum IgE and tear IgE have been found. T lymphocytes and eosinophils are important components of AKC’s pathogenesis. See Table 27-2 for immune findings.

Diagnosis

AKC is typically bilateral, with symptoms ranging from moderate to severe ocular and periocular itching, tearing, burning, mucous discharge, and photophobia. Extraocular atopy occurs frequently in patients who have AKC; eczema is found in 100% of cases and allergic rhinitis in approximately 65%.The presence of other atopic findings assists in the diagnosis of AKC. A family history of atopy is found in at least 50% of patients.

Lid involvement in AKC includes dermatitis, found in 62.2% of cases, as well as blepharitis, meibomianitis, trichiasis, ectropion, entropion, and madarosis. The lids may be eczematous and may appear red, indurated, and crusted. Infraorbital lid edema may cause a skin crease known as Dennie-Morgan line.

In patients with AKC there is conjunctival hyperemia, erythema, injection, and chemosis (Figure 27-8). Papillary changes, diffuse in presentation, affect the inferior palpebral conjunctiva more commonly than the superior. Less frequently, giant papillae and follicles may be found. Conjunctival fibrosis and scarring may occur, along with symblepharon formation.

Corneal involvement, in the form of superficial punctate keratopathy of the epithelium, is common and is found in 100% of patients. More serious changes include corneal ulceration, with subsequent loss of vision in 70% of patients, neovascularization, pannus, and scarring. Other corneal findings include Trantas’ dots, keratoconus, and filamentary keratitis.

Cataracts of some degree occur in approximately 10% of AKC patients and, in one series, in 25% of patients with severe recurrent disease. Posterior subcapsular cataracts

Figure 27-8 Atopic conjunctivitis.

are the most common form of cataract, followed by anterior subcapsular cataracts, and then by changes throughout the entire lens. More typically, the lens changes are minimal, with simple fleck opacities observed in the lens. In some cases, however, significant changes may occur, and reduced vision may necessitate cataract removal.Teenagers with AKC are most susceptible to cataracts. Once the cataract develops it progresses quickly, sometimes maturing in weeks. Cataract removal may be required as soon as a year after onset of visual disturbances.

Patients with AKC are prone to staphylococcal blepharitis and herpes simplex keratitis.This may be associated with a depressed T-cell function.

AKC is differentiated from other allergic diseases, most notably by its association with atopic dermatitis. However,other important diagnostic clues include lack of a seasonal association, age at onset, inferior conjunctival involvement, and longevity of the clinical manifestations of the disease.

Management

Treatment of AKC depends on severity of symptoms and the secondary manifestations. Mild clinical manifestations may be managed with environmental controls, cold compresses, vasoconstrictors, and topical antihistamines. However, treatment often includes oral antihistamines, mast cell stabilizers, steroids, and, in more severe cases, cyclosporine.

Lid eczema may be treated with steroid ointments or creams, such as hydrocortisone 1%, and, in severe cases, with systemic steroids (prednisone).Topical steroids may be required to prevent corneal and conjunctival scarring.

When blepharitis and meibomianitis are present, treatment includes maintenance of good lid hygiene and use of topical antibiotics or antibiotic–steroid combinations. In some cases systemic antibiotics such as tetracycline may be necessary.

In difficult-to-treat sight-threatening cases of AKC, topical cyclosporine A 2% and 0.05% have been found to be

568 CHAPTER 27 Allergic Eye Disease

an effective and safe treatment. In the most severe cases oral cyclosporine, 3 to 5 mg/kg/day may be necessary; however, significant side effects include renal or nephrotoxicity and arterial hypertension.

Amniotic membrane patching is a treatment option with difficult-to-manage corneal manifestations, such as ulcers. The amniotic membrane acts like a bandage contact lens, stabilizing the epithelium and limiting cytokine and inflammatory cell access to the cornea.

ALLERGIC DISORDERS OF THE EYELIDS

Eyelid inflammation is a common result of exposure to allergens. The thin tissue of the eyelids and its highly vascularized nature make it a common site for allergic response. The eyelids share many common features with the conjunctiva, and because the bulbar and palpebral conjunctivas are continuous, there is a predisposition to inflammation from an immunologic hypersensitivity reaction. Consequently, the clinical features of the allergic response of the conjunctiva and lids often overlap. In addition, the eyelid skin is a frequent site for microbial colonization, in particular by Staphylococcus, which makes it susceptible to a variety of combination reactions.

Allergic disorders of the eyelid include atopic dermatitis, contact dermatitis, and urticaria. Eczema is a common feature of both atopic and contact dermatitis. Table 27-5 summarizes the clinical manifestations and management of each entity.

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory skin disorder that affects the epidermis and is characterized by eczema and itching. Two percent of the adult population is afflicted by atopic dermatitis, often with the earliest manifestation first appearing in childhood.The peak incidence occurs during the fourth or fifth decade.There is a family tendency as well as a predisposition to allergy and asthma. Periorbital inflammation is a common manifestation of atopy. Acute manifestations include exudative lesions, erythema, and edema. Chronic manifestations include dry scaly lesions with lichenification.

Etiology

The pathogenesis of atopic dermatitis remains unclear, although there appears to be a relation to IgE, along with a genetic influence. Although investigators have focused on a dysfunctional immune system, there is no conclusive evidence to support the assumption that cell-mediated response occurs in atopic dermatitis. Elevated serum IgE levels may be found.

Diagnosis

The patient often demonstrates a bilateral chronic inflammation of the eyelids, characterized by dryness of the skin of the eyelids, tylosis, punctal scarring, and,

in extreme cases, symblepharon and cicatrization. Typically, lesions occur on the face in infants; in flexural areas in older children;and in flexural areas,hands,wrists, feet, ankles, and face (especially the forehead and around the eyes) in adults. Diagnosis is based on itchy skin, along with a history of asthma or hay fever, dry skin, and dermatitis affecting the typical locations of the forehead, cheeks, or flexural areas.

Pruritic and inflamed periocular skin is a common eyelid manifestation of periorbital dermatoses. The poor ability of involved skin to bind water in atopic disease decreases the resistance to irritants and allergens and promotes inflammation. Red itchy eyes are accompanied by erythema, edema, and fine scaling of the eyelids. Papules and fine fissures are sometimes noted, and if the condition is chronic, normal skin lines become thickened and accentuated. Chronic rubbing leads to exacerbation of the symptoms, and brown discoloration of the upper eyelids can be observed. Referred to as lichen simplex chronicus, the changes appear to be more common in women and Asian individuals and result from a repeated rubbing cycle.

Other specific and nonspecific markers of atopic dermatitis have been recognized and include lid edema, a midline lower eyelid crease that extends to the outer canthus (Dennie-Morgan infraorbital fold), periorbital darkening, madarosis, ectropion, ptosis, and trichiasis. Staphylococcal infestation of the eyelids can cause infectious eczema and can lead to chronic blepharitis, a common accompanying response to the liberated toxins of the staphylococcal microorganism. Chronic anterior blepharitis can result in an array of signs and symptoms, including itching; burning; foreign body sensation; thickening, induration, and pitting of the eyelids; loss of lashes; conjunctival hyperemia; and, in severe cases, marginal corneal involvement. Atopic dermatitis also appears to have an increased association with herpes simplex dermatitis, molluscum contagiosum, and superinfection.

Numerous ocular findings have been reported in atopic dermatitis, including keratoconus and cataracts. In the case of keratoconus, eye rubbing has been proposed as a causative factor, although the typical patient does not develop keratoconus earlier in life. Cataract formation appears to have a genetic predisposition and may be exacerbated by the use of corticosteroids, a mainstay for treating the atopic patient. Marginal punctate keratitis and corneal infiltrates or ulceration often accompany the blepharitic process. Additional cutaneous findings are also seen in atopic patients, typically involving the extensor and flexural surfaces. In the case of the latter manifestation, moisture and scratching and rubbing of the skin due to the severe pruritus are causative factors.

Differential diagnosis includes irritant contact dermatitis and allergic contact dermatitis. History of exposure to an offending substance assists in making the differential diagnosis.

Table 27-5

Allergic Lid Disease: Etiology, Immunology, Clinical Manifestations, and Management

HSV = herpes simplex virus; NSAIDs = nonsteroidal anti-inflammatory drugs; SPK = superficial punctate keratopathy.

Disease Eye Allergic 27 CHAPTER

570 CHAPTER 27 Allergic Eye Disease

Management

Treatment should initially be directed toward decreasing xerosis and subsequent pruritus. Avoidance of rubbing breaks the “itch–scratch” cycle that leads to exacerbation of inflammation and of symptoms. Application of cool damp compresses for 15 to 30 minutes decreases itching. Compresses should be followed by the application of a soothing preservativeand fragrance-free emollient, such as white petrolatum. Oral antihistamines such as hydroxyzine hydrochloride or chlorpheniramine maleate are prescribed to relieve itching. Patients should be informed of their sedating effects and should be advised to take one dose 1 hour before bedtime to lessen or relieve pruritus during sleep.

Topical corticosteroids are used in cases of exacerbation and should be applied sparingly to the affected area. Hydrocortisone 1% twice a day or dexamethasone 0.1% applied to the periorbital area helps to relieve symptoms during these periods. Secondary infection manifested as blepharitis or keratoconjunctivitis should be treated with topical ophthalmic antibiotic ointments such as bacitracin or erythromycin.Topical antihistamines, NSAIDs, or mast cell stabilizers can be used to control itching, and topical steroids are sometimes required to treat severe keratoconjunctivitis associated with the atopic response. Because of side effects, steroids are not indicated for longterm use.

Topical calcineurin inhibitors are also used to treat atopic dermatitis and include pimecrolimus (Elidel) and tacrolimus (Protopic).Treatment effects are seen in 1 to 3 weeks. Adverse reactions most commonly include burning. Although a causal relation has not been established, rare skin malignancy and lymphoma have been reported.

Contact Dermatitis

Contact dermatitis occurs from an environmental “contact” of an offending agent that results in the hallmark clinical manifestation of eczema. Contact dermatitis may be divided into allergic and irritant (nonallergic) varieties. Clinically, the two types may be indistinguishable. Irritant contact dermatitis affects two-thirds of all contact dermatitis sufferers, versus one-third affected by the allergic type. Irritant contact dermatitis results from a single concentration-dependent exposure to the offending agent and occurs within 1 to 24 hours of exposure. In contrast, allergic contact dermatitis requires a sensitizing exposure, with minimal subsequent reexposure necessary to cause a reaction. Contact dermatitis from topical ophthalmic medications is of an irritant or toxic nature in 90% of cases, with an allergic response accounting for only 10%.

Etiology

The heightened sensitivity of the eyelid skin increases susceptibility to contact dermatitis. Inflammation of the

skin of the lids occurs from hypersensitivity or from exposure to irritants. Exposure to offending agents may result from airborne allergens, inadvertent touching or rubbing of the eyelids, use of ophthalmic medication, or cosmetic use.

The allergic variety of contact dermatitis is a type IV hypersensitivity response involving sensitization of T lymphocytes. Antigens form after the sensitizing substance (haptens or partial antigens) comes into contact with the dermal protein for the first time, which results in sensitization. Sensitization may take weeks to years to develop. On reexposure to the same or a related substance, a delayed inflammatory response is elicited, usually within 48 to 72 hours. Allergic contact dermatitis is often associated with the eyelids or periocular area and in some instances may involve the face and the hands.

Irritant contact dermatitis is a less specific inflammation and does not result from prior exposure and sensitization.

Box 27-1 summarizes a variety of offending substances that are involved in contact dermatitis, which include

Box 27-1 Offending Agents in Contact Dermatitis

Contact lens solutions Medications

Antibiotics

Aminoglycosides (gentamicin, tobramycin, neomycin)

Chloramphenicol, polymyxin B, sulfacetamide Antivirals

Idoxuridine, trifluridine, vidarabine Steroids

Mydriatics/anticholinergics Phenylephrine, atropine, scopolamine, homatropine, tropicamide

Topical anesthetics Proparacaine

Glaucoma

Betaxolol, timolol, brimonidine, dorzolamide, carbachol, pilocarpine, echothiophate, epinephrine, dipivefrin, levobunolol

Vehicles

Propylene glycol Preservatives

Thimerosol, benzalkonium chloride Metals

Nickel

Rubber (eyelash curlers) Other

Makeup

Shampoo Fingernail polish Perfumes