Does Allergic Conjunctivitis Always Require Prescription Eyedrops?

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1-MINUTE CONSULT ALEXEI GONZALEZ-ESTRADA, MD LISANNE P. NEWTON, MD Assistant Professor, Department of Internal Medicine, Department of Allergy and Immunology, Quillen College of Medicine, East Tennessee State Pediatric Institute, Cleveland Clinic University, Johnson City

BRIEF ANSWERS TO SPECIFIC CLINICAL QUESTIONS Q: Does allergic conjunctivitis always require prescription eyedrops?

No, not all patients with allergic con- onset. It can also be perennial, from year- A: junctivitis need prescription eyedrops. round exposure to indoor allergens such as For mild symptoms, basic nonpharmaco- animal dander, dust mites, and mold. logic eye care often suffi ces. Advise the patient Allergic conjunctivitis often occurs togeth- to avoid rubbing the eyes, to use artifi cial tears er with allergic rhinitis, which is also caused as needed, to apply cold compresses, to limit by exposure to aeroallergens and is character- or temporarily discontinue contact lens wear, ized by nasal congestion, pruritus, rhinorrhea and to avoid exposure to known allergens. (anterior and posterior), and sneezing.2 Topical therapy with an over-the-counter Pollen is more commonly associated with eyedrop that combines an antihistamine and a rhinoconjunctivitis, whereas dust mite allergy mast cell stabilizer is another fi rst-line measure. is more likely to cause rhinitis alone. Prescription eyedrops are usually reserved for patients who have persistent bothersome An immunoglobulin E-mediated reaction symptoms despite use of over-the-counter eye- Allergic conjunctivitis is a type I immunoglob- drops. Also, some patients have diffi culty with ulin E-mediated immediate hypersensitivity For most the regimens for over-the-counter eyedrops, reaction. In the early phase, ie, within minutes since most must be applied two to four times of allergen exposure, previously sensitized mast patients, per day. In addition, patients with concomi- cells are exposed to an allergen, causing de- basic eye care tant allergic rhinitis may benefi t from an in- granulation and release of infl ammatory media- tranasal corticosteroid. tors, primarily histamine. The late phase, ie, 6 measures to 10 hours after the initial exposure, involves are sufﬁ cient ■ ALLERGIC CONJUNCTIVITIS: an infl ux of infl ammatory cells such as eosino- A BRIEF OVERVIEW phils, basophils, and neutrophils.3 Allergic conjunctivitis, caused by exposure of Differential diagnosis the eye to airborne allergens, affects up to 40% The differential diagnosis of allergic con- of the US population, predominantly young junctivitis includes infectious conjunctivitis, adults.1 Bilateral pruritus is the chief symp- chronic dry eye, preservative toxicity, giant tom. The absence of pruritus should prompt papillary conjunctivitis, atopic keratocon- consideration of a more serious eye condition. junctivitis, and vernal keratoconjunctivitis.3 Other common symptoms of allergic con- Giant papillary conjunctivitis is an infl am- junctivitis include redness, tearing (a clear, matory reaction to a foreign substance, such watery discharge), eyelid edema, burning, and as a contact lens. Atopic keratoconjuncti- mild photophobia. Some patients may have vitis and vernal keratoconjunctivitis can be infraorbital edema and darkening around the vision-threatening and require referral to an eye, dubbed an “allergic shiner.”1 ophthalmologist. Atopic keratoconjuncti- Allergic conjunctivitis can be acute, with vitis is associated with eczematous lesions sudden onset of symptoms upon exposure to of the lids and skin, and vernal keratocon- an isolated allergen. It can be seasonal, from junctivitis involves chronic infl ammation of exposure to pollen and with a more gradual the palpebral conjunctivae. Warning signs doi:10.3949/ccjm.82a.14162 include photophobia, pain, abnormal fi nd-

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TABLE 1 Eyedrops for allergic conjunctivitis Over the Dose counter? Estimated costa Topical antihistamine Emedastine difumarate (Emadine) 5 mL 1 drop every 6 hours No $124 Mast-cell stabilizers Cromolyn sodium (Crolom, Opticrom) 10 mL 1 drop every 6 hours Yes $38–$51 Lodoxamide tromethamine (Alomide) 10 mL 1 drop every 6 hours No $141 Nedocromil sodium (Alocril) 5 mL 1–2 drops every 12 hours No $152 Pemirolast (Alamast) 10 mL 1–2 drops every 6 hours No $119 Combination topical antihistamine and mast-cell stabilizer eyedrops Alcaftadine (Lastacaft) 3 mL 1 drop daily No $149 Azelastine HCl 0.05% (Optivar) 6 mL 1 drop every 12 hours No $43 Bepostastine besilate (Bepreve) 5 mL 1 drop every 12 hours No $173 Epinastine HCl (Elestat) 5 mL 1 drop every 12 hours No $61 Ketotifen 0.025% (Alaway 10 mL, Zaditor 5 mL) 1 drop every 12 hours Yes $15–$70 Olopatadine HCl 0.1% (Patanol) 5 mL 1 drop every 6–8 hours No $212 Olopatadine HCl 0.2% (Pataday) 2.5 mL 1 drop daily No $156 a Estimated costs, August 2015, Cleveland, OH. Tailor ings on pupillary examination, blurred vi- Avoidance treatment sion (unrelated to excessively watery eyes), Triggers for the allergic reaction, such as pol- to symptoms, unilateral eye complaints, and ciliary fl ush.2 len, can be identifi ed with aeroallergen skin Bacterial conjunctivitis is highly conta- testing by an allergist. But simple avoidance allergen proﬁ le, gious and usually presents with hyperemia, measures are helpful, such as closing windows, and patient “stuck eye” upon awakening, and thick, puru- using air conditioning, limiting exposure to lent discharge. It is usually unilateral. Symp- the outdoors when pollen counts are high, preferences toms include burning, foreign-body sensation, wearing sunglasses, showering before bedtime, and discomfort rather than pruritus. Patients avoiding exposure to animal dander, and us- with allergic conjunctivitis may have con- ing zippered casings for bedding to minimize comitant bacterial conjunctivitis and so re- exposure to dust mites.3 quire a topical antibiotic as well as treatment Patients who wear contact lenses should for allergic conjunctivitis. reduce or discontinue their use, as allergens Viral conjunctivitis usually affects one eye, adhere to contact lens surfaces. is self-limited, and typically presents with oth- Topical therapies er symptoms of a viral syndrome. If avoidance is not feasible or if symptoms persist despite avoidance measures, patients ■ MANAGEMENT OPTIONS should be started on eyedrops. Management of allergic conjunctivitis consists Eyedrops for allergic conjunctivitis are of basic eye care, avoidance of allergy triggers, classifi ed by mechanism of action: topical and over-the-counter and prescription topical antihistamines, mast-cell stabilizers, and com- and systemic therapies, as well as allergen im- bination preparations of antihistamine and munotherapy.3 mast-cell stabilizer (Table 1). Algorithms for

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Currently, the only over-the-counter eye- TABLE 2 drops for allergic conjunctivitis are cromolyn Three steps to treating allergic conjunctivitis (a mast-cell stabilizer) and ketotifen 0.025% (a combination antihistamine and mast-cell Step 1 stabilizer). Most drops for allergic conjuncti- Avoid allergens (guided by allergy testing, if available) vitis are taken two to four times a day. Two Avoid rubbing the eyes once-daily eyedrop formulations for allergic Use artiﬁ cial tears conjunctivitis—available only by prescrip- Limit contact lens use tion—are olopatadine 0.2% and alcaftadine. Apply cold compresses However, these are very expensive (Table 1) and so may not be an appropriate choice for Step 2 some patients. On the other hand, a study Continue Step 1 recommendations from the United Kingdom4 found that pa- Over-the-counter eyedrops tients using olopatadine made fewer visits to (combination antihistamine and mast-cell stabilizer) their general practitioner than patients using Intranasal corticosteroid for concomitant allergic rhinitis cromolyn, resulting in lower overall cost of healthcare. Results of studies of patient prefer- Step 3 ences and effi cacy of olopatadine 0.1% (twice- Prescription eyedrops daily preparation) vs ketotifen 0.025% are (combination antihistamine and mast-cell stabilizer) mixed,5–8 and no study has compared olopata- Intranasal corticosteroid for concomitant allergic rhinitis Consider referral a dine 0.2% (once-daily preparation) with over- Consider allergen immunotherapy b the-counter ketotifen. Consider a short course of an oral corticosteroid if symptoms Adverse effects of eyedrops are severe, acute, or persistent Common adverse effects include stinging and a Consider referral to an allergist at any step to identify allergic triggers, including burning immediately after use; this effect may relevant pollens for timing of medications before season onset; see text for differential be reduced by keeping the eyedrops in the re- diagnosis and red ﬂ ags that should prompt a referral to an ophthalmologist; topical frigerator. Patients who wear contact lenses corticosteroid eye drops should only be prescribed with close follow-up with an ophthalmologist. should remove them before using eyedrops b For refractory cases or cases in which medications have undesirable side effects, are for allergic conjunctivitis, and wait at least 10 limited by adherence, or are undesired; allergen immunotherapy is the only disease- minutes to replace them if the eye is no longer modifying treatment available; not indicated for acute relief of symptoms. red.2 Antihistamine drops are contraindicated in patients at risk for angle-closure glaucoma. Whenever possible, patients with seasonal managing allergic conjunctivitis exist2 but are allergic conjunctivitis should begin treatment based on expert consensus, since there are no 2 to 4 weeks before the relevant pollen season, randomized clinical trials with head-to-head as guided by the patient’s experience in past comparisons of topical agents for allergic con- seasons or by the results of aeroallergen skin junctivitis. testing. This modifi es the “priming” effect, in In our practice, we use a three-step ap- which the amount of allergen required to in- proach to treat allergic conjunctivitis (Table duce an immediate allergic response decreases 2). Combination antihistamine and mast-cell with repeated exposure to the allergen. stabilizer eyedrops are the fi rst line, used as ■ OTHER TREATMENT OPTIONS needed, daily, seasonally, or year-round, based on the patient’s symptoms and allergen pro- Vasoconstrictor or decongestant eyedrops are in- fi le. Antihistamine or combination eyedrops dicated to relieve eye redness but have little or are preferred as they have a faster onset of ac- no effect on pruritus, and prolonged use may lead tion than mast-cell stabilizers alone,3 which to rebound hyperemia. Thus, they are not gen- have an onset of action of 3 to 5 days. The erally recommended for long-term treatment of combination drops provide an effect on the allergic conjunctivitis.3 Also, patients with glau- late-phase response and a longer duration of coma should be advised against long-term use of action. over-the-counter vasoconstrictor eyedrops.

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Corticosteroid eyedrops are reserved for subcutaneous immunotherapy, and sublingual refractory and severe cases. Their use requires tablet immunotherapy, recently approved by the close follow-up with an ophthalmologist to US Food and Drug Administration.9 Subcuta- monitor for complications such as increased neous immunotherapy targets specifi c aeroaller- intraocular pressure, infection, and cataracts.2 gens for patients allergic to multiple allergens. Patients presenting with an acute severe The new sublingual immunotherapy tablets tar- episode of allergic conjunctivitis that has not get only grass pollen and ragweed pollen.9 Most responded to oral antihistamines or combi- patients in the United States are polysensi- nation eyedrops may be treated with a short tized.10 Both forms of immunotherapy can result course of an oral corticosteroid, if the benefi t in sustained effectiveness following discontinu- outweighs the risk in that patient. ation. Sublingual therapy may be administered Oral antihistamines are generally less effec- year-round, before allergy season, or during al- tive than topical ophthalmic agents in reliev- lergy season (depending on the type of allergy). ing ocular allergy symptoms and have a slower onset of action.2 They are useful in patients ■ TAILORING TREATMENT who have an aversion to instilling eyedrops on a regular basis or who wear contact lenses. We recommend a case-by-case approach to the For patients who have associated allergic rhi- management of patients with allergic conjunc- nitis—ie, most patients with allergic conjuncti- tivitis, tailoring treatment to the patient’s symp- vitis—intranasal corticosteroids and intranasal toms, allergen profi le, and personal preferences. antihistamines are the most effective treatments For example, if adherence is a challenge for rhinitis and are also effective for allergic we recommend a once-daily combination conjunctivitis. Monotherapy with an intranasal eyedrop (olopatadine 0.2%, or alcaftadine). If medication may provide suffi cient relief of con- cost is a barrier, we recommend the combina- junctivitis symptoms or allow ocular medication over-the-counter drop (ketotifen). tions to be used on a less frequent basis. Medications may be used during allergy Allergen immunotherapy season or year-round depending on the pa- Referral to an allergist for consideration of al- tient’s symptom and allergen profi le. Patients lergen immunotherapy is an option when avoid- whose symptoms are not relieved with these ance measures are ineffective or unfeasible, when measures should be referred to an allergist for fi rst-line treatments are ineffective, and when the further evaluation and management, or to an patient does not wish to use medications. ophthalmologist to monitor for complications Allergen immunotherapy is the only disease- of topical steroid use and other warning signs, modifying therapy available for allergic con- as discussed earlier, or to weigh in on the dif- junctivitis. Two forms are available: traditional ferential diagnosis. ■ ■ REFERENCES 6. Ganz M, Koll E, Gausche J, Detjen P, Orfan N. Ketotifen fumarate and olopa- 1. Bielory L, Friedlaender MH. Allergic conjunctivitis. Immunol Allergy Clin tadine hydrochloride in the treatment of allergic conjunctivitis: a real-world North Am 2008; 28:43–58. comparison of effi cacy and ocular comfort. Adv Ther 2003; 20:79–91. 7. Aguilar AJ. Comparative study of clinical effi cacy and tolerance in 2. Bielory L, Meltzer EO, Nichols KK, Melton R, Thomas RK, Bartlett JD. An seasonal allergic conjunctivitis management with 0.1% olopatadine algorithm for the management of allergic conjunctivitis. Allergy Asthma hydrochloride versus 0.05% ketotifen fumarate. Acta Ophthalmol Scand Proc 2013; 34:408–420. Suppl 2000; 230:52–55. 3. Wallace DV, Dykewicz MS, Bernstein DI, et al; Joint Task Force on Practice; 8. Artal MN, Luna JD, Discepola M. A forced choice comfort study of American Academy of Allergy; Asthma & Immunology; American College olopatadine hydrochloride 0.1% versus ketotifen fumarate 0.05%. Acta of Allergy; Asthma and Immunology; Joint Council of Allergy, Asthma Ophthalmol Scand Suppl 2000; 230:64–65. and Immunology. The diagnosis and management of rhinitis: an updated 9. Cox L. Sublingual immunotherapy for aeroallergens: status in the practice parameter. J Allergy Clin Immunol 2008; 122(suppl 2):S1–S84. United States. Allergy Asthma Proc 2014; 35:34–42. 4. Guest JF, Clegg JP, Smith AF. Health economic impact of olopatadine 10. Salo PM, Arbes SJ Jr, Jaramillo R, et al. Prevalence of allergic sensitization in compared to branded and generic sodium cromoglycate in the treat- the United States: results from the National Health and Nutrition Examina- ment of seasonal allergic conjunctivitis in the UK. Curr Med Res Opin tion Survey (NHANES) 2005-2006. J Allergy Clin Immunol 2014; 134:350–359. 2006; 22:1777–1785. 5. Leonardi A, Zafi rakis P. Effi cacy and comfort of olopatadine versus ADDRESS: Lisanne P. Newton, MD, Department of Allergy and Clinical ketotifen ophthalmic solutions: a double-masked, environmental study Immunology, Respiratory Institute, A120, Cleveland Clinic, 9500 Euclid of patient preference. Curr Med Res Opin 2004; 20:1167–1173. Avenue, Cleveland, OH 44195; e-mail: [email protected]

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