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INTRODUCTION — Allergic conjunctivitis is caused by airborne allergens contacting the eye, which leads to immunoglobulin E (IgE)-mediated local mast cell degranulation and allergic inflammation. It typically presents as bilateral ocular pruritus, redness, and watery discharge. This topic discusses the management of allergic conjunctivitis. The clinical manifestations, epidemiology, diagnosis, and differential diagnosis are reviewed separately. (See "Allergic conjunctivitis: Clinical manifestations and diagnosis".)
An overview of conjunctivitis and detailed reviews of other types of conjunctivitis are found elsewhere. (See "Conjunctivitis" and "Vernal keratoconjunctivitis" and "Atopic keratoconjunctivitis" and "Giant papillary conjunctivitis" and "Toxic conjunctivitis".)
Basic eye care — There are several general measures that are helpful to most patients with allergic conjunctivitis:
●Patients should not rub their eyes because rubbing can cause mechanical mast cell degranulation and worsening of symptoms.
●Cool compresses can help reduce eyelid and periorbital edema .
●Patients should reduce or stop use of contact lenses during symptomatic periods, given the propensity of allergens to adhere to contact lens surfaces.
Allergen avoidance — Avoidance or reduction of contact with known allergens and appropriate management of environmental exposure are critical to effective management of allergic conjunctivitis, especially in more severe cases.
●Preventive steps to reduce symptoms of seasonal allergic conjunctivitis (SAC) include use of air conditioning when possible, limiting outdoor exposure, and keeping car and home windows closed during the peak pollen seasons.
●For patients with perennial allergic conjunctivitis (PAC), prevention includes avoidance of the specific allergens that are causing symptoms in a specific patient. For those allergic to dust mites, helpful measures include replacing old pillows, blankets, and mattresses; using dust mite allergen impermeable covers for pillows, comforters, and mattresses; frequently washing beddings; reducing humidity; and frequently vacuuming and dusting the home. Additionally, other reservoirs of dust should be removed, such as old carpets, old furniture, and old curtains or drapes. When the culprit allergen is animal dander, the animal may need to be removed from the home, and old carpets, furniture, and curtains should be removed or cleaned thoroughly. The avoidance and reduction of indoor allergen levels are reviewed separately. (See "Allergen avoidance in the treatment of asthma and allergic rhinitis".)
Avoidance measures for indoor allergens can be expensive, and some clinicians prefer to pursue testing for sensitivity to specific allergens by an allergist prior to recommending involved allergen remediation measures. (See 'Referral' below.)
OVERVIEW OF THERAPIES — The therapies used in the management of allergic conjunctivitis, mechanisms of action, dosing, and adverse effects are discussed in this section. Treatment strategies for specific disorders are discussed subsequently. (See 'Treatment for specific disorders' below.)
Topical therapies — Topical therapies include antihistamine/vasoconstrictor combination products, antihistamines with mast cell stabilizing properties, mast cell stabilizers, and, for refractory symptoms, topical glucocorticoids (table 1).
Vasoconstrictor/antihistamine combinations — Eye drops containing both an antihistamine and a vasoconstrictor are widely available without a prescription. Although we do not specifically recommend these products if a patient presents for treatment, some patients have accessed these medications on their own. The antihistamine component competitively and reversibly blocks histamine receptors in the conjunctiva and eyelids, thus inhibiting the actions of the primary mast cell-derived mediator. The vasoconstrictor component activates the postjunctional, alpha-adrenergic receptors found in blood vessels, causing vasoconstriction and decreased conjunctival edema. Examples of topical antihistamine/vasoconstrictor drugs include naphazoline and pheniramine (available as Naphcon-A, Opcon-A, Visine-A, and others). Dosing is up to four times daily during acute symptoms.
These topical medications are appropriate for short-term (eg, less than two weeks) or episodic use only. Regular use for longer than two weeks can lead to rebound hyperemia because of the vasoconstrictor component . Patients should understand that they may have increased eye redness for several days when they stop using these medications. (See 'Acute allergic conjunctivitis' below.)
Single agent topical products (ie, vasoconstrictors or antihistamines only) are also available without a prescription, although the combination products usually work better .
Antihistamines with mast cell-stabilizing properties — Antihistamines with mast cell stabilizing properties include olopatadine (Patanol, Pataday, Pazeo), alcaftadine (Lastacaft), bepotastine (Bepreve), azelastine HCl (Optivar), epinastine (Elestat), ketotifen fumarate (generic, Ketotifen), and emedastine (Emadine). Ketotifen fumarate is available in a generic formulation and does not require a prescription (in the United States).
These agents have two main actions:
●As antihistamines, they competitively and reversibly block histamine receptors in the conjunctiva and eyelids, thus inhibiting the actions of the primary mast cell-derived mediator . This also helps reduce the late phase of the allergic response.
●As mast cell stabilizers, they inhibit mast cell degranulation, limiting the release of histamine, tryptase, and prostaglandin D2 (PGD2). Release of these proinflammatory mast cell mediators is the first step in the allergic cascade. These drugs also inhibit leukocyte activity and dampen mediator release from basophils, eosinophils, and neutrophils .
Dosing is twice per day for most products. Pataday, Pazeo, and Lastacaft are once-daily preparations. Onset of action is within minutes for most drugs. However, at least two weeks of therapy should be allowed in order to assess the full efficacy of prophylactic therapy with these agents, since it may take some time for the inflammation to be controlled and symptoms to subside completely.
Common side effects include stinging and burning upon instillation. Patients may find it helpful to refrigerate the drops and/or use refrigerated artificial tears before using these medications. Other adverse effects include headache and increased ocular dryness.
Mast cell stabilizers — Mast cell stabilizing agents include cromolyn sodium (generic, Opticrom), nedocromil (Alocril), lodoxamide-tromethamine (Alomide), and pemirolast (Alamast). Full efficacy is reached 5 to 14 days after therapy has been initiated and therefore these medicines are NOT useful for acute symptoms . In addition, dosing of mast cell stabilizers is four times daily, compared with twice daily for most agents with combined actions. Because of these limitations, mast cell stabilizers are often impractical, but they may provide an option for patients with seasonal allergic conjunctivitis (SAC) who do not tolerate other therapies and can anticipate when their symptoms will start. Such patients should begin treatment two to four weeks before the pollen season. However, for most patients, antihistamines with mast cell stabilizing properties are more convenient and effective:
●One randomized study compared the use of cromolyn sodium (4 percent, four times daily) for two weeks prior to allergen challenge with a single drop of ketotifen fumarate (0.025 percent) given just before allergen challenge. The single drop of ketotifen was superior in controlling itching and redness at 15 minutes and at 4 hours after challenge .
●An analysis comparing the economic cost with the United Kingdom's National Health Service of prescribing olopatadine or cromolyn concluded that the more expensive olopatadine resulted in sufficiently fewer return visits than it was for the more cost-effective option .
Nonsteroidal antiinflammatory drugs — Nonsteroidal antiinflammatory drugs (NSAIDs) block the action of cyclooxygenase and inhibit the conversion of arachidonic acid to prostaglandins and thromboxanes. Topical NSAIDs do have efficacy compared with placebo in the treatment of allergic conjunctivitis . However, they are less effective than topical antihistamines, and thus have limited utility in most cases [10,11].
Glucocorticoids — Topical glucocorticoid preparations may be considered in patients with refractory symptoms. However, they have potentially serious side effects that can be vision threatening, and their use should be supervised by an ophthalmologist. (See 'Refractory symptoms' below.)
Glucocorticoids suppress the late-phase reaction of allergic inflammation . They inhibit phospholipase A2, and, consequently, reduce the formation of lipid-derived mediators from arachidonic acid. This prevents leukocyte migration, hydrolytic enzyme release, fibroblast growth, and changes in vascular permeability.
Topical glucocorticoids should only be used for short "pulse therapy" of two weeks maximal duration in patients for whom antihistamines with mast cell stabilizing properties have not controlled symptoms adequately. Ocular side effects from glucocorticoids can be vision threatening and include cataract formation, elevated intraocular pressure (IOP), glaucoma, and secondary infections.
"Soft" steroids are a group of topical glucocorticoids that have a greatly reduced risk of causing increased IOP since they are formulated such that they undergo rapid inactivation upon penetration of the cornea . "Soft" steroids include Lotemax and Alrex (loteprednol), Vexol (rimexolone), Pred Mild (prednisolone), FML (fluorometholone), HMS (medrysone). The side effect risk profile is lowest with the newer generation steroids (loteprednol and rimexolone). Loteprednol is also available as a suspension, as a gel, and in 0.2 and 0.5 percent concentrations.
"Soft" steroids are administered two to four times per day for approximately two weeks. This can help slow the immune response so that the mast cell stabilizers, antihistamines, and artificial tears have a greater chance to work. In contrast, use of these medications for greater than six weeks is associated with a significantly increased risk of complications.
Topical glucocorticoids that have a much higher risk of raising IOP include prednisolone acetate (1 percent) and dexamethasone phosphate (0.1 percent). We do not recommend use of these agents by clinicians who are not experts in ophthalmology. These preparations are indicated for severe inflammation.
Use of multiple eye drops — For patients using multiple types of eye drops, such as a topical medication and artificial tears, it is advisable to space drops a few (three to five) minutes apart if possible, so that instillation of a second drop does not wash out the first. These recommendations need to be balanced with the lifestyle limitations and realities faced by the patient. In addition, closure of the eyelids for a few seconds after drug instillation helps absorption into ocular tissues. In contrast, repetitive blinking should be avoided as much as possible, as it generates negative pressure and causes topical medications to wash out of the ocular surface more quickly.
Systemic therapies — Oral antihistamines are often used in the management of allergic conjunctivitis that is associated with nonocular symptoms.
Oral antihistamines — Oral, nonsedating, over-the-counter, or prescription H1 antihistamines may be helpful for patients who also report rhinitis and generalized pruritus. However, when ocular symptoms are the main presenting problem, topical (ocular) medications are preferred because they are faster acting and less likely to cause systemic side effects. In addition, randomized trials have shown that topical medications are more effective than oral therapies for ocular symptoms. Specifically, topical olopatadine was more effective than oral loratadine or fexofenadine, and topical ketotifen was more effective than oral desloratadine [14-16]. In addition, oral antihistamines can cause drying of mucosal membranes and decreased tear production in some patients, especially those with concomitant dry eye . (See 'Concomitant dry eyes' below.)
Nonsedating oral antihistamines available without a prescription include fexofenadine (generic, Allegra), loratadine (generic, Claritin), cetirizine (generic, Zyrtec). Cetirizine causes sedation in up to 10 percent of patients, despite its categorization as nonsedating. In the United States, desloratadine (Clarinex) and levocetirizine (Xyzal) require a prescription. Dosing is discussed elsewhere. (See "Pharmacotherapy of allergic rhinitis", section on 'Second- and third-generation antihistamines'.)
Several oral antihistamines have demonstrated efficacy in the treatment of allergic conjunctivitis, compared with placebo, in studies of varying rigor [18-20]. Oral administration of antihistamines results in peak serum levels in 30 minutes to 3 hours, depending on the specific drug. Full effects are seen after several days of use. Thus, these agents have a slower onset of action compared with topical agents, although this is not relevant if they are taken prophylactically.
TREATMENT FOR SPECIFIC DISORDERS
Acute allergic conjunctivitis — Most cases of acute allergic conjunctivitis are self-limited (usually lasting less than 24 hours) and do not require long-term treatment, as mentioned previously. A common example of acute allergic conjunctivitis occurs in the cat-allergic patient who visits a home with a resident cat. The mainstay of management is future avoidance of the allergen.
If pharmacologic treatment is needed, then several options exist (table 1):
●Over-the-counter topical antihistamine/vasoconstrictors are usually sufficient in treating symptoms of short duration (eg, less than two weeks). Patients should be advised that these products are intended for short-term or episodic use only . (See 'Vasoconstrictor/antihistamine combinations' above.)
●Topical antihistamines with mast cell stabilizing properties are also effective in this setting. (See 'Antihistamines with mast cell-stabilizing properties' above.)
●Oral, nonsedating, over-the-counter or prescription antihistamines are another option for occasional acute allergic conjunctivitis. However, topical agents are faster acting and less likely to cause systemic side effects, and are therefore preferred when ocular symptoms are the main presenting problem, as previously discussed. (See 'Oral antihistamines' above.)
Anticipated exposures — For patients who can anticipate exposures to a specific allergen and premedicate, use of a topical antihistamine with mast cell stabilizing properties beginning the day before the exposure and continuing for a day after the exposure is usually effective in partially or completely preventing symptoms.
Frequent episodes — For frequent attacks of acute allergic conjunctivitis (ie, occurring more than two days per month), a topical antihistamine with mast cell stabilizing properties is a better choice than a preparation containing a vasoconstrictor (because of the rebound hyperemia associated with long-term vasoconstrictor use). (See 'Antihistamines with mast cell-stabilizing properties' above.)
Seasonal and perennial allergic conjunctivitis — Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are managed similarly.
Preferred agents — Topical antihistamines with mast cell stabilizing properties are the agents of choice in treating SAC and PAC, since they address both the acute and more chronic aspects of these conditions. Other useful agents include topical mast cell stabilizers and oral antihistamines. However, each of the latter options has limitations compared with combination topical mast cell stabilizer/antihistamine medications. (See 'Mast cell stabilizers' above and 'Oral antihistamines' above.)
For patients with SAC, treatment should be initiated at least two to four weeks before the anticipated onset of symptoms whenever possible to optimize effectiveness. The onset of SAC can often be predicted based upon the patient's experience in past seasons. This approach will result in superior symptom control compared with initiating therapy once symptoms have developed. (See 'Antihistamines with mast cell-stabilizing properties' above.)
Patients with concomitant rhinitis — In patients with concomitant allergic rhinitis, the addition of an intranasal glucocorticoid or an oral antihistamine can be helpful.
In a randomized study, olopatadine combined with fluticasone propionate nasal spray was superior to olopatadine combined with oral fexofenadine . The relative merits of intranasal glucocorticoids and oral antihistamines in the treatment of allergic rhinitis are reviewed elsewhere. (See "Pharmacotherapy of allergic rhinitis".)
REFRACTORY SYMPTOMS — A minority of patients with persistent symptoms will not achieve control of their allergic conjunctivitis after two or three weeks of consistent therapy with a topical antihistamine with mast cell stabilizing properties. Reasons for treatment failure include severe disease, the presence of concomitant dry eye, coexisting toxic conjunctivitis, and incorrect diagnosis. The differential diagnosis of allergic conjunctivitis is discussed separately. (See "Allergic conjunctivitis: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)
Referral — For patients with refractory symptoms, referral to an ophthalmology or allergy expert is appropriate:
●Referral to an ophthalmologist is highly recommended for patients who do not respond to two or three weeks of consistent therapy with an antihistamine/mast cell stabilizer agent. Ophthalmology experts will evaluate for other disorders, especially concomitant drug eye, and may prescribe additional therapy, such as topical glucocorticoids. Patients whose disease is severe enough to require topical glucocorticoids should also be referred to an allergist for definitive identification of the culprit allergen and possible allergen immunotherapy.
●Referral to an allergy specialist for possible skin testing is indicated for severe allergic conjunctivitis that is not controlled adequately by standard therapy and initial attempts at allergen avoidance. Patients with coexisting allergic rhinitis and asthma that is not well controlled are also candidates for referral.
Allergy specialists can assist the patient in the correct identification and avoidance of the culprit allergens, help guide pharmacotherapy, and offer allergen immunotherapy to appropriate patients. Injection (subcutaneous) allergen immunotherapy (SCIT) is the best established form of immunotherapy. SCIT is a three- to five-year process that involves the gradual administration of increasing amounts of allergen to induce protective immunologic responses. Sublingual forms of immunotherapy are also available for some allergens. Immunotherapy is the only means of altering the abnormal immune response that underlies allergic disease in a semipermanent manner. (See "Subcutaneous immunotherapy for allergic disease: Indications and efficacy", section on 'Efficacy in allergic rhinitis' and "Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma".)
Concomitant dry eyes — Tear film insufficiency, or dry eyes, is an extremely common disorder, particularly among women and older adults. All patients with allergic conjunctivitis who do not respond fully to the standard treatments outlined previously should be evaluated for concomitant dry eyes by an eye care practitioner. The ophthalmologist will perform a thorough slit lamp evaluation along with other testing to assess the status of the patient's lacrimal functional unit to determine the severity of dry eye disease and possible etiologies. Simply asking whether the eyes feel dry may not adequately detect affected patients, as those with mild to moderate dry eyes may not report symptoms. Dry eye is mentioned briefly here and discussed in more detail separately. (See "Dry eyes".)
Dry eye can coexist with allergic conjunctivitis and worsen it through two mechanisms :
●Concentration of allergen is higher with tear film insufficiency
●Ability to rinse away the offending allergen is diminished
Signs of tear film insufficiency include superficial punctate-keratopathy, reduced tear break-up time, and decreased production of tears as measured by the Schirmer's test. Various medications, such as oral antihistamines, can exacerbate tear film insufficiency because they cause a decrease in tear production due to their anticholinergic effects.
Concomitant toxic conjunctivitis — Coexisting toxic conjunctivitis should be considered in patients with refractory symptoms and is discussed separately. (See "Toxic conjunctivitis".)
Need for more aggressive therapy — In a minority of patients with severe allergic conjunctivitis, topical antihistamines with mast cell stabilizing properties are inadequate to control symptoms. In such patients, topical "soft" steroid preparations may be considered. However, they should only be used for short "pulse therapy," no longer than two weeks in duration, and treatment should be supervised by an ophthalmologist, as discussed previously. (See 'Glucocorticoids' above.)
Topical cyclosporine and tacrolimus have been used off label and in highly varied dosing schedules and concentrations for severe allergic eye disease [23-25]. However, there are no clear guidelines for the use of these agents, and efficacy data from randomized trials comparing them with topical glucocorticoids are lacking.
SPECIAL POPULATIONS — Management of allergic rhinitis in pregnant women and young children begins with optimizing allergen avoidance and general nonpharmacologic measures. (See 'Initial measures' above.)
Pregnant women — If nonpharmacologic measures and allergen avoidance do not control symptoms adequately, cromolyn sodium eye drops (generic, Opticrom) may be tried next. The dose is one or two drops per eye, four times daily and cromolyn takes one to two weeks to be fully effective. If allergen exposure is predictable (eg, pollen season), therapy should be initiated two weeks before. (See 'Mast cell stabilizers' above.)
If cromolyn sodium drops are not sufficient, various antihistamine drops may be administered. Although these agents were assigned a category C by the US Food and Drug Administration (FDA) in the past, reports of adverse effects are lacking and most ophthalmologists are comfortable with their safety. Of note, this categorization system is being retired . (See 'Antihistamines with mast cell-stabilizing properties' above.)
Topical glucocorticoids should be used with caution in pregnant women and under the supervision of both an ophthalmologist and an obstetrician. Issues surrounding use of topical glucocorticoids in pregnancy are discussed separately. (See "Recognition and management of allergic disease during pregnancy", section on 'Glucocorticoid nasal sprays'.)
Allergen immunotherapy is another option for severe symptoms. Immunotherapy is not initiated during pregnancy, although it may be continued in women who were already receiving it, tolerating it, and deriving benefit. (See "Recognition and management of allergic disease during pregnancy", section on 'Allergen immunotherapy'.)
Vasoconstrictor and decongestant eye drops are generally avoided during pregnancy.
Young children — The approach to treating allergic conjunctivitis in young children is similar to that in adults. Many of the topical medications are approved for children as young as two years of age (table 1).
Children with severe symptoms should be referred to an allergist for consideration of allergen immunotherapy, which can address the underlying allergic disease in a more permanent manner. Sublingual immunotherapy is another form of allergen immunotherapy that is widely available in many parts of the world, and became available in 2014 in the United States for some pollens. (See "Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Allergic conjunctivitis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●General management of allergic conjunctivitis includes instructions to not rub the eyes, to discontinue the use of contact lenses during symptomatic periods, to apply cool compresses, and to liberally use refrigerated artificial tears throughout the day. (See 'Initial measures' above.)
●Allergen avoidance measures are important in all forms of allergic conjunctivitis. These are reviewed separately. (See "Allergen avoidance in the treatment of asthma and allergic rhinitis".)
●For patients requiring short-term treatment (ie, two weeks or less) to reduce symptoms, over-the-counter topical antihistamine/vasoconstrictor preparations may be adequate. The vasoconstrictor component reduces redness and conjunctival edema, but can cause rebound hyperemia beyond two weeks of use. Examples include naphazoline HCl/pheniramine maleate (Naphcon-A, Opcon-A, Visine-A, and others). Dosing is up to four times daily. (See 'Acute allergic conjunctivitis' above.)
●For patients with frequent episodes (ie, occurring more than two days per month), and for those with seasonal or perennial allergic conjunctivitis, we recommend a topical antihistamine with mast cell stabilizing properties in preference to other therapies (Grade 1A). Examples include olopatadine (Patanol, Pataday, Pazeo), alcaftadine (Lastacaft), bepotastine (Bepreve), azelastine HCl (Optivar), epinastine (Elestat), and ketotifen fumarate (generic, Ketotifen) (table 1). Onset of action is within minutes for most drugs. At least two weeks of therapy should be allowed in order to assess the full efficacy of these agents. (See 'Frequent episodes' above and 'Seasonal and perennial allergic conjunctivitis' above.)
•For patients with seasonal allergic conjunctivitis (SAC), treatment should be initiated at least two to four weeks before the pollen season to optimize effectiveness. (See 'Seasonal and perennial allergic conjunctivitis' above.)
•In patients with concomitant allergic rhinitis, the addition of an intranasal glucocorticoid spray is more effective than a nonsedating oral antihistamine. (See 'Patients with concomitant rhinitis' above.)
•In patients who also have dry eyes, oral antihistamines can worsen dry eye symptoms and should be avoided. (See 'Oral antihistamines' above.)
●Patients with severe ocular symptoms that persist despite at least three weeks of antihistamines/mast cell stabilizer therapy should be referred to an ophthalmologist for confirmation of the diagnosis, evaluation for concomitant dry eye, and further management. A short course of a topical "soft" steroid preparation may be required to control symptoms. (See 'Refractory symptoms' above and 'Glucocorticoids' above.)
●Patients who wish to minimize use of medications, cannot adequately avoid the culprit allergen(s), or have severe and recurrent symptoms despite appropriate medications should be referred to an allergy specialist. Allergen immunotherapy may be appropriate for such patients. (See 'Referral' above.)
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