Rx Perspective
Outsmarting Allergic Conjunctivitis
Therapies based on new insights bring our patients relief.

Allergic conjunctivitis is the most frequently occurring ocular condition seen in general practice. It affects more than 50 million Americans, causes extreme discomfort, and significantly impairs a patient's quality of life.

Fortunately, our ability to treat it has improved dramatically in the past few years. Today, dual- and multiple-action agents are available, which prevent mast-cell mediator release and recruitment of eosinophils and have a potent antihistaminic effect. The end result is much more efficacious therapy, which is also better tolerated and accepted by patients for regular use.

Furthermore, the enhanced ability of these agents to control allergic inflammation may result in a steroid-sparing effect. While steroids are needed most of the time to treat the more severe forms of ocular allergy, namely vernal keratoconjunctivitis and atopic keratoconjunctivitis, these newer agents appear to lessen that need.

TREATING BEYOND EARLY-PHASE INFLAMMATION

Historically, primarily due to a lack of understanding of the underlying pathogenesis, treatment of allergic conjunctivitis was based only on symptom relief and amelioration of clinical features.

Older therapies, which include vasoconstrictors, mainly alpha-adrenergic agents, reduce ocular redness by constricting blood vessels. Antihistamines, alone or in combination with vasoconstrictors, compete with histamine for binding at the H1 and H2 receptor sites, located on nerve endings and vascular endothelial cells, to prevent the common symptoms of itching, redness, tearing and chemosis.

However, because of their lack of effect on mediator release and late-phase inflammation, these drugs are only partially effective in relieving our patients' symptoms.

In addition, these over-the-counter agents may cause tachyphylaxis, rebound conjunctivitis and a permanent loss of ocular vessel tone with chronic use. Decreased accommodation, anisocoria, and blurred vision have also been reported with these older agents.

NEW THERAPIES AT A GLANCE

The newer therapeutic drops, including antihistamines and mast-cell stabilizers, alone or in combinations, are highly effective because they treat more than the early-phase reaction. They're often employed as monotherapy and have the added benefit of increasing patient and physician awareness of the importance of allergic conjunctivitis.

Here's a brief review of the newest agents, based on my experience:

• pemirolast potassium (Alamast) is a mast-cell stabilizer indicated for the prevention of ocular itching due to allergic conjunctivitis. It inhibits activation and release of allergic mediators.
• nedocromil sodium (Alocril), another mast-cell stabilizer, is indicated for the treatment of ocular itching and inhibits the release of mast-cell mediators. It is significantly more potent than an older agent, cromolyn sodium (Crolom), in mast-cell stabilization.
  Both pemirolast potassium and nedocromil sodium may need to be used more regularly for optimal benefit due to a lack of antihistaminic activity.
• olopatadine hydrochloride (Patanol) is a well-tolerated dual action combination antihistamine/mast cell stabilizer. Use generally results in relief of acute symptoms, as well as a more prolonged effect due to inhibition of mast-cell mediator release. It is indicated for treatment of the signs and symptoms of allergic conjunctivitis.
• azelastine hydrochloride (Optivar), while technically an antihistamine, has a multiple-action effect on mast-cell release and eosinophil inhibition. An effect on nasal cytokine concentration has also been shown. Like olopatadine, it is dosed twice daily.
• ketotifen fumarate (Zaditor) is a combination antihistamine/mast-cell stabilizer with distinct anti-inflammatory actions, including direct inhibition of eosinophil chemotaxis, activation and degranulation. Dosed twice daily, it can relieve ocular itching in 3 to 5 minutes, and provide a duration of action up to 12 hours.

EACH OF THESE NEW COMPOUNDS IS UNIQUE

All of these new agents represent a significant advance in our understanding and treatment of ocular allergies. However, each agent is unique, and the practicing clinician must use his or her judgment and clinical experience when choosing an agent for a particular individual. Important factors to consider:

• the agent's effect on acute symptoms and its ability to provide longer-duration relief
• how well patients tolerate the agent
• what side effects each agent was shown to produce in clinical trials and whether the data hold true in practice
• convenience of, and likely compliance with, dosage requirements.

Some of the medications have been shown to have therapeutic effects beyond their labeled indications.

Further studies and clinical experience will determine which agents are more effective and may result in greater symptom relief along with less use of ancillary medication.

Dr. Ganz, of the Ganz Allergy & Asthma Center in Racine, Wis., is board certified in Allergy & Immunology and is also an assistant clinical professor of medicine at the Medical College of Wisconsin.