Allergic Conjunctivitis
The primary methods used to evaluate ocular allergy medications are the conjunctival allergen challenge (CAC) and environmental studies. The CAC model was developed as a modification of the conjunctival provocation test to minimize variability seen with the allergen challenge model. The CAC model appears to provide comparable results to environmental studies within a more controlled setting especially when evaluating topical antihistamines.
Numerous classes of agents, both systemic and topical, have been used to manage the signs and symptoms of allergic conjunctivitis ( Table 3 ). Ocular surface lubricants such as isotonic saline, artificial tears, and ointments help to rinse antigens from the eye. Many of these products are available over-the-counter. However, these agents do not have direct efficacy on allergic mediators. These provide only temporary relief and have little or no effect on moderate-to-severe ocular allergy. They may also contain preservatives such that when used excessively, they can add insult to the already irritated ocular surface. Topical decongestants (vasoconstrictors) are α-agonists that act to reduce redness and edema. Overuse of these agents, however, can cause mydriasis (pupil dilation) and lead to rebound hyperemia of the conjunctiva. Generally speaking, vasoconstrictors are not recommended for treating ocular allergies, as the topical antihistamines are safer and more effective.
In recent years, topical antihistamines have become the mainstay of management for allergic conjunctivitis. The benefits of these agents are that they block histamine, stabilize the mast cell, and inhibit eosinophil activation and migration. Topical antihistamines address the signs and symptoms of ocular allergy, particularly itching. In a few cases these can cause local irritation and other side-effects, but these are more prevalent in older generation medications. Systemic antihistamines can be used, in some cases, but these medications tend to dry the ocular surface. For patients without comorbidities such as rhinitis, topical ophthalmic agents are preferred to administration of systemic antihistamines.
Mast cell stabilizers (inhibitors) prevent degranulation of mast cells. These agents are particularly effective in SAC and PAC in which the predominant cell types are the mast cell and eosinophil. Mast cell stabilizers address both the early and late phases of the allergic response.
Combination antihistamine/vasocontrictor (histamine blocker and α agonist) eyedrops are now available. These medications address itching, redness, and edema. Some tend to be slower in their onset of action, and relatively short acting. These can also cause sedation or excitability. Rebound hyperemia of the conjunctiva is also a concern.
A popular treatment in use today is the topical antihistamine/mast cell stabilizer (i.e. alcaftadine, azelastine, bepotastine, epinastine, and olopatadine.) These dual-acting medications relieve redness, hyperemia, itching, and irritation. They have a quick onset of action, which is likely to improve patient adherence compared with the pure mast cell stabilizers. Several of these agents require only once-a-day or twice-a-day dosing. Side-effects, which tend to be transient and mild, include: stinging, burning, bitter taste, cold symptoms, and sedation.
NSAIDs can address the itching associated with allergic conjunctivitis; however, only ketorolac tromethamine 0.5% has a Food And Drug Administration (FDA)-approved indication for the treatment of SAC. In general, NSAIDs are used in the management of postoperative pain and inflammation after cataract surgery but not as a first-line therapy for ocular allergies. These agents can cause discomfort upon instillation, which can in turn lead to reduced patient adherence.
Topical corticosteroids (i.e. loteprednol etabonate) inhibit the inflammatory process and are used for the acute phase of the allergic response. These agents provide relief from most ocular signs and symptoms of SAC. Historically, chronic corticosteroid use has been reported to carry a liability of increased intraocular pressure (IOP). However, loteprednol reportedly has a low propensity to cause elevations in IOP. The risk of cataract formation historically associated with steroids is also low for the more recently developed molecules. In the case of loteprednol, the C-20 ester corticosteroid structure prevents the formation of Schiff base intermediates with lens proteins as occurs with C20 ketone corticosteroid molecules.
Optimally, the treatment of allergic conjunctivitis should be based on severity ( Table 4 ). For the patient with mild signs and symptoms, education can be helpful in managing the disease. Many of the lifestyle modification factors that benefit ocular allergy sufferers are applicable to allergy sufferers in general, including:
When optimizing lifestyle factors proves inadequate, artificial tears can help rinse allergens from the ocular surface. Finally, topical antihistamines and/or mast cell stabilizers can be prescribed to provide symptom relief.
In addition to the above treatments, other prescription medications can be added or substituted for patients with moderate allergic conjunctivitis. Topical antihistamines/mast cell stabilizer agents provide dual actions to eliminate the signs and symptoms of ocular allergies. Corticosteroids can be added to the regimen administered in a brief pulse fashion during the acute phase. Avoid certain ophthalmic preservatives (i.e. benzalkonium choride) for patients who appear to be sensitive, particularly those suffering from chronic dry eye, as their ocular surface may already be compromised.
For patients with severe signs and symptoms, topical antihistamines/mast cell stabilizers in combination with a stronger corticosteroid may be warranted. Individuals in this group are candidates for referral/comanagement as their condition will require a more aggressive treatment approach. Immunomodulators, such as cyclosporine A, tacrolimus, and pimecrolimus inhibit calcineurin and can be used as replacement therapy for corticosteroids, when long-term therapy is required. Tacrolimus ointment has been reported to reduce inflammatory cells, particularly eosinophils, in conjunctival cytology samples taken from atopic blepharoconjunctivitis patients. Cyclosporine A has shown some benefit in patients with AKC and VKC. However, it should be noted that these are off-label, unapproved uses of the product. The most common adverse effect of topical cyclosporine A is burning.
Treatment strategies for PAC are similar to those for SAC. Corticosteroids are beneficial for the early phase of treatment as pulse therapy. Topical antihistamines/mast cell stabilizers are effective for maintenance therapy throughout the year. Patients taking topical or systemic antihistamines, who are prone to dry eye, should be monitored for worsening of their symptoms.
Allergen-specific immunotherapy (SIT) can be effective for patients with severe allergic conjunctivitis/rhinoconjunctivitis. Increasing doses of the allergen are administered by the subcutaneous immunotherapy (SCIT) or sublingual immunotherapy route to achieve hyposensitization. Side-effects, including anaphylaxis, are known to occur with this form of therapy. SIT requires a long-term commitment from the patient and/or caregiver in terms of time (i.e. SCIT requires monthly injections for 3 years) and expense. This may not be practical for the SAC patient who does not suffer from other comorbidities.
Treatment
The primary methods used to evaluate ocular allergy medications are the conjunctival allergen challenge (CAC) and environmental studies. The CAC model was developed as a modification of the conjunctival provocation test to minimize variability seen with the allergen challenge model. The CAC model appears to provide comparable results to environmental studies within a more controlled setting especially when evaluating topical antihistamines.
Numerous classes of agents, both systemic and topical, have been used to manage the signs and symptoms of allergic conjunctivitis ( Table 3 ). Ocular surface lubricants such as isotonic saline, artificial tears, and ointments help to rinse antigens from the eye. Many of these products are available over-the-counter. However, these agents do not have direct efficacy on allergic mediators. These provide only temporary relief and have little or no effect on moderate-to-severe ocular allergy. They may also contain preservatives such that when used excessively, they can add insult to the already irritated ocular surface. Topical decongestants (vasoconstrictors) are α-agonists that act to reduce redness and edema. Overuse of these agents, however, can cause mydriasis (pupil dilation) and lead to rebound hyperemia of the conjunctiva. Generally speaking, vasoconstrictors are not recommended for treating ocular allergies, as the topical antihistamines are safer and more effective.
In recent years, topical antihistamines have become the mainstay of management for allergic conjunctivitis. The benefits of these agents are that they block histamine, stabilize the mast cell, and inhibit eosinophil activation and migration. Topical antihistamines address the signs and symptoms of ocular allergy, particularly itching. In a few cases these can cause local irritation and other side-effects, but these are more prevalent in older generation medications. Systemic antihistamines can be used, in some cases, but these medications tend to dry the ocular surface. For patients without comorbidities such as rhinitis, topical ophthalmic agents are preferred to administration of systemic antihistamines.
Mast cell stabilizers (inhibitors) prevent degranulation of mast cells. These agents are particularly effective in SAC and PAC in which the predominant cell types are the mast cell and eosinophil. Mast cell stabilizers address both the early and late phases of the allergic response.
Combination antihistamine/vasocontrictor (histamine blocker and α agonist) eyedrops are now available. These medications address itching, redness, and edema. Some tend to be slower in their onset of action, and relatively short acting. These can also cause sedation or excitability. Rebound hyperemia of the conjunctiva is also a concern.
A popular treatment in use today is the topical antihistamine/mast cell stabilizer (i.e. alcaftadine, azelastine, bepotastine, epinastine, and olopatadine.) These dual-acting medications relieve redness, hyperemia, itching, and irritation. They have a quick onset of action, which is likely to improve patient adherence compared with the pure mast cell stabilizers. Several of these agents require only once-a-day or twice-a-day dosing. Side-effects, which tend to be transient and mild, include: stinging, burning, bitter taste, cold symptoms, and sedation.
NSAIDs can address the itching associated with allergic conjunctivitis; however, only ketorolac tromethamine 0.5% has a Food And Drug Administration (FDA)-approved indication for the treatment of SAC. In general, NSAIDs are used in the management of postoperative pain and inflammation after cataract surgery but not as a first-line therapy for ocular allergies. These agents can cause discomfort upon instillation, which can in turn lead to reduced patient adherence.
Topical corticosteroids (i.e. loteprednol etabonate) inhibit the inflammatory process and are used for the acute phase of the allergic response. These agents provide relief from most ocular signs and symptoms of SAC. Historically, chronic corticosteroid use has been reported to carry a liability of increased intraocular pressure (IOP). However, loteprednol reportedly has a low propensity to cause elevations in IOP. The risk of cataract formation historically associated with steroids is also low for the more recently developed molecules. In the case of loteprednol, the C-20 ester corticosteroid structure prevents the formation of Schiff base intermediates with lens proteins as occurs with C20 ketone corticosteroid molecules.
Optimally, the treatment of allergic conjunctivitis should be based on severity ( Table 4 ). For the patient with mild signs and symptoms, education can be helpful in managing the disease. Many of the lifestyle modification factors that benefit ocular allergy sufferers are applicable to allergy sufferers in general, including:
Allergen avoidance – avoid being outdoors during times when pollen counts are high
Avoidance of animal exposure for sensitive individuals
Hypoallergenic bedding
Washing sheets in hot water, which denatures allergenic proteins (i.e. those from dust mites)
Showering and shampooing at bedtime to remove allergens
Sunglasses, which serve as a barrier to airborne allergens
Avoidance of eye rubbing – rubbing can introduce allergens into the eye and/or cause the release of more inflammatory mediators
Eyelid cleansers – foam cleansers and wipes help to remove allergens from the lids and lashes
Cool compresses – help to alleviate ocular itching
When optimizing lifestyle factors proves inadequate, artificial tears can help rinse allergens from the ocular surface. Finally, topical antihistamines and/or mast cell stabilizers can be prescribed to provide symptom relief.
In addition to the above treatments, other prescription medications can be added or substituted for patients with moderate allergic conjunctivitis. Topical antihistamines/mast cell stabilizer agents provide dual actions to eliminate the signs and symptoms of ocular allergies. Corticosteroids can be added to the regimen administered in a brief pulse fashion during the acute phase. Avoid certain ophthalmic preservatives (i.e. benzalkonium choride) for patients who appear to be sensitive, particularly those suffering from chronic dry eye, as their ocular surface may already be compromised.
For patients with severe signs and symptoms, topical antihistamines/mast cell stabilizers in combination with a stronger corticosteroid may be warranted. Individuals in this group are candidates for referral/comanagement as their condition will require a more aggressive treatment approach. Immunomodulators, such as cyclosporine A, tacrolimus, and pimecrolimus inhibit calcineurin and can be used as replacement therapy for corticosteroids, when long-term therapy is required. Tacrolimus ointment has been reported to reduce inflammatory cells, particularly eosinophils, in conjunctival cytology samples taken from atopic blepharoconjunctivitis patients. Cyclosporine A has shown some benefit in patients with AKC and VKC. However, it should be noted that these are off-label, unapproved uses of the product. The most common adverse effect of topical cyclosporine A is burning.
Treatment strategies for PAC are similar to those for SAC. Corticosteroids are beneficial for the early phase of treatment as pulse therapy. Topical antihistamines/mast cell stabilizers are effective for maintenance therapy throughout the year. Patients taking topical or systemic antihistamines, who are prone to dry eye, should be monitored for worsening of their symptoms.
Allergen-specific immunotherapy (SIT) can be effective for patients with severe allergic conjunctivitis/rhinoconjunctivitis. Increasing doses of the allergen are administered by the subcutaneous immunotherapy (SCIT) or sublingual immunotherapy route to achieve hyposensitization. Side-effects, including anaphylaxis, are known to occur with this form of therapy. SIT requires a long-term commitment from the patient and/or caregiver in terms of time (i.e. SCIT requires monthly injections for 3 years) and expense. This may not be practical for the SAC patient who does not suffer from other comorbidities.