Conjunctivitis - Allergic, Seasonal & Perennial Management

Lubricants (Ophthalmic)¹

Lubricants consist of a saline solution combined with wetting and viscosity agents, which is used 2-6 times/day as needed. Non-preserved formulations are recommended if these will be used frequently to prevent allergic reactions secondary to preservatives. Formulations with Hyaluronic acid have been shown to improve wound healing and to prevent dryness. Lubricants increase the bioavailability of active pharmaceutical compounds in combined formulations due to the high viscosity of Hyaluronic acid. These assist in the removal and dilution of allergens that come in contact with the eye surface, such as cooled artificial tears. Lubricants do not alter the pathophysiology of the disease but treat co-existing tear deficiency. Washing the eyes frequently with water decreases the integrity of the layer of tears; hence, artificial tears may be used instead. Numerous lubricants that differ by class, osmolarity, and electrolyte composition are available. These may be sufficient for mild symptoms.

¹Various ophthalmic lubricants are available. Please see the latest MIMS for specific formulations and prescribing information.

Antihistamines (Ophthalmic)

Example drugs: Alcaftadine, Bilastine, Cetirizine, Emedastine, Levocabastine

Antihistamines compete for the histamine receptor sites. In the conjunctiva, stimulation of the H₁ receptor mediates symptoms of pruritus, while the H₂ receptor is involved in vasodilation. These reduce itching and vasodilation.

Bilastine is approved by the European Medicines Agency as a preservative-free ophthalmic solution for use in allergic conjunctivitis. This has a fast onset of action and efficacy for as long as 16 hours post-administration. This is suitable for once-daily dosing. An ophthalmic formulation of Cetirizine has been approved by the United States Food and Drug Authority (US FDA) for use in allergic conjunctivitis. Clinical trials showed significant reduction in ocular itching and hyperemia with an acceptable safety profile. This contains BAK as a preservative to maintain the sterility of the formulation. Emedastine was shown to be more effective than Levocabastine in decreasing chemosis, eyelid swelling, and other signs and symptoms of seasonal allergic conjunctivitis. This is a selective H₁ antagonist with no adrenergic, dopaminergic, or serotonergic effect.

Ophthalmic antihistamines provide immediate ocular relief as compared to oral antihistamines. These may be used as monotherapy or in combination with decongestants/vasoconstrictors in treating signs and symptoms of allergic conjunctivitis. Antihistamine or vasoconstrictor preparations may be used for short-term treatment (≤2 weeks) of acute allergic conjunctivitis. Antihistamines with decongestants or vasoconstrictors should not be used for >2 weeks without medical advice.

Ophthalmic antihistamines should not be used for >6 weeks without medical advice. Prolonged use of antihistamines that are non-selective may cause ciliary muscle paralysis, mydriasis, and photophobia, especially when used by patients with lighter irises. These may also cause angle-closure glaucoma, particularly in patients who are at risk (ie history of narrow-angle glaucoma, patients with narrow angles).

Antihistamines/Mast Cell Stabilizers (Ophthalmic)

Example drugs: Azelastine, Bepotastine, Epinastine, Ketotifen, Olopatadine 

Conjunctivitis - Allergic, Seasonal and Perennial_Management 2

Antihistamines/mast cell stabilizers have both mast cell-stabilizing and antihistaminic activity. These bind to H₁ and H₂ receptors, stabilize mast cell, and down-regulate inflammatory markers that affect early and late phases of the conjunctival allergic response. These may be used for either acute or chronic diseases. Antihistamines/mast cell stabilizers relieve acute symptoms (eg ocular itchiness and redness) and prevent recurrence of allergic conjunctivitis. These are fast-acting, effective, and generally well tolerated. For patients with seasonal allergic conjunctivitis, begin treatment at least 2-4 weeks prior to pollen season for optimal effectivity.

Antihistamines (Oral)

Oral antihistamines may be used as adjunctive therapy for moderate to severe allergic conjunctivitis and as a treatment option for occasional acute allergic conjunctivitis. These are useful in cases accompanied by non-ocular allergies (eg allergic rhinitis). Oral antihistamines are inferior to ophthalmic antihistamines primarily due to a 1- to 2-hour delay from systemic administration to delivery to ocular tissues but have a longer duration of action. These are more likely than topical antihistamines to cause side effects and may be associated with drying of mucosal membranes and decreased tear production, especially in patients with concomitant dry eye.

Mast Cell Stabilizers (Ophthalmic)

Example drugs: Cromoglicic acid, Lodoxamide, Nedocromil, Pemirolast

Mast cell stabilizers inhibit degranulation of mast cells, which limits the release of inflammatory mediators and platelet-activating factor. These are used for prevention of symptoms and for conditions that are recurrent or persistent. These have a slower onset of action as compared to antihistamines. The effects of Cromoglicic acid are evident 2-5 days after the initiation of the therapy, with maximum improvement of ocular symptoms after 15 days.

Mast cell stabilizers require multiple applications every day to show effects. These are most useful in the seasonal management of chronic allergic diseases of the eye. These are more effective when used prophylactically with a loading period and administered before the triggering of an allergic reaction. Mast cell stabilizers are usually given to patients with moderate symptoms after an ophthalmic decongestant has been administered to provide immediate relief.

Studies have shown that Lodoxamide is more effective than Cromoglicic acid in reducing eosinophil activation and clinical signs and symptoms. Pemirolast was shown to specifically inhibit mast cell degranulation, thus preventing the release of chemical mediators like histamine. Mast cell stabilizers may also help in improving symptoms of allergic rhinitis. These are generally well tolerated and may be used as long as needed.

Nonsteroidal Anti-inflammatory Drugs (Ophthalmic)

Example drugs: Diclofenac, Ketorolac

Ophthalmic nonsteroidal anti-inflammatory drugs inhibit the activity of cyclooxygenase, blocking the production of prostaglandins. These help reduce ocular signs and symptoms like itching or conjunctival hyperemia and do not mask ocular infections, affect wound healing or intraocular pressure (IOP), nor contribute to cataract formation. The use of ophthalmic nonsteroidal anti-inflammatory drugs should be limited to severe forms of seasonal and perennial allergic conjunctivitis or for severe exacerbations that cannot be controlled by other measures.

Vasoconstrictors (Ophthalmic)

Example drugs: Naphazoline, Phenylephrine, Tetrahydrozoline

Ophthalmic vasoconstrictors are sympathomimetic agents. These decrease vascular congestion and eyelid edema but do not affect allergic response. These are usually used in combination with ophthalmic antihistamines and have been shown to have a synergistic effect. Based on studies, Naphazoline plus Antazoline or Pheniramine was comparable in decreasing the signs and symptoms of allergic conjunctivitis. Chronic use (>10 days) of ophthalmic vasoconstrictors may cause conjunctivitis medicamentosa and rebound vasodilation after cessation of use.

Corticosteroids (Ophthalmic)

Ophthalmic corticosteroids should be given and supervised by an ophthalmologist. These reduce inflammatory cytokine production, mast cell proliferation, and cell-mediated immune response. Ophthalmic corticosteroids may be considered for use in the treatment of severe and chronic ocular allergy. These block inflammatory pathways that perpetuate the persistent and chronic forms of ocular allergy.

Ophthalmic corticosteroids may be used when a patient's symptoms have not responded to other agents. A 1- to 2-week course can be added to antihistamine/mast cell stabilizers if symptoms are not controlled. The lowest potency and frequency that relieves the patient’s symptoms should be given. These should only be used for a short period of time (≤2 weeks). Chronic use of topical steroids is associated with glaucoma, cataract formation, and infections of the cornea and conjunctiva. Inappropriate use in herpes simplex, fungal, and other viral or bacterial keratitis may cause complications that may threaten vision (eg corneal melting, perforation, and scarring).

Immunotherapy







Immunotherapy is used in patients with atopic disorders like seasonal allergic conjunctivitis, perennial allergic conjunctivitis, allergic rhinitis, or asthma. This desensitizes a patient against a specific allergen; however, ocular symptoms take longer than nasal symptoms. Topical Cyclosporine or Tacrolimus may be used in severe conditions. Cyclosporine A limits type IV allergic responses, thereby reducing infiltration of eosinophils. Tacrolimus reduces the action of T cells. Giant papillae and corneal lesions as well as total sign and symptom scores are reduced in refractory disease. Immunotherapy needs careful monitoring by a specialist. Its use is limited by cost, long-term patient commitment, and the possibility of anaphylaxis. 

General Eye Care Measures

Avoid excessive eye rubbing, as this may cause worsening of symptoms and degranulation due to mechanical disruption of mast cells. Apply a cold compress to reduce symptoms such as eyelid and periorbital edema. Cold compresses cause vasoconstriction, which can improve patient comfort by reducing itching. Reduce or avoid the use of contact lenses during seasonal flare-ups. Use eyelid cleansers to remove allergens.

Avoidance of Trigger Factors

To avoid trigger factors associated with allergic conjunctivitis, preventive measures such as closing the windows, filtering the air, removing pets and stuffed toys, and vacuuming and dusting regularly should be done. This is the mainstay of managing allergic conjunctivitis. Trial of avoidance may identify antigens. The use of glasses (eg goggle-type, sunglasses) is recommended during the pollen-flying period. Sensitive patients should attempt to limit exposure to the outdoors during times of high pollen count or other allergen counts. House mites are common allergens and can be reduced by using dust mite-proof encasings on pillows and mattresses and washing sheets in hot water. Washing clothes frequently and bathing before bedtime may be helpful.