Therapeutic Insights
Mast Cell Stabilizers
Advice for using these agents to treat allergic conditions in pregnant patients and contact lens wearers.

By Robert B. DiMartino, O.D., M.S., Lafayette, Calif.

Seasonal allergic conjunctivitis is prevalent in the United States, with estimates that up to 20% of Americans suffer from some degree of this condition.

Research efforts are underway to better understand how mast cells are sensitized, with the hope of finding ways to stop the degranulation of the cells. Unfortunately, this research has a long way to go before finding a clinical therapy that will solve this problem.

In the interim, stabilizing mast cells has been an effective approach to treating external ocular immune conditions including seasonal allergic conjunctivitis, giant papillary conjunctivitis (GPC) and vernal keratoconjunctivitis (VKC).

Artificial tears

The antigens and preformed substances, such as histamines and the metabolized mediators of allergy, are concentrated in the tear film. Diluting the tears with artificial tears is an effective treatment for relieving allergic eye disease.

Although these topical drops are safe and effective, their usefulness in treating acute disease is somewhat limited. Effective mast cell stabilization often requires sustained treatment of 2 to 4 weeks. There are exceptions to this clinical observation. One of the newer mast cell stabilizers, nedocromil sodium 2% (Alocril), is reported to reduce symptoms in less time than older mast cell stabilizers. It's thought that nedocromil has other actions such as inhibiting allergic chemotaxis. These secondary actions help effectively relieve symptoms of acute allergic reactions.

Choosing your approach

You can choose from many approaches to treat allergic disease with mast cell stabilizers.

If a patient has a well-documented history of seasonal allergic conjunctivitis, consider pre-emptive treatment. I often start treatment at least 2 weeks before the typical onset of seasonal symptoms. I prescribe an old favorite -- lodoxamide tromethamine 0.1% (Alomide) or the newer agent, pemirolast potassium 0.1% (Alamast) -- on a q.i.d. basis, for 2 to 4 weeks before the historical onset of symptoms.

Continue therapy for the balance of allergy season, and you'll often spare the patient his first attack of allergic disease. Re-member that lodoxamide and pemirolast are available in 10-ml bottles and because you'll treat both eyes, you'll use a total of eight drops per day.

You can continue this therapy for up to 3 months, outlasting all but the most protracted allergy seasons. Three prescription refills will allow patients to complete the treatment cycle.

Pregnancy considerations

Because we often prescribe mast cell stabilizers for extended periods of time, we must consider the potential effects during pregnancy. Agents in this category of drugs are either Pregnancy Category B or C.

• Pregnancy Category B refers to reproductive studies in research animals that have failed to demonstrate adverse birth implications, but no studies have been conducted in humans. Use medicines in this category only if clearly indicated.
• Pregnancy Category C denotes that adverse birth implications were present in research animals. No well-controlled studies have been performed in humans and although animal studies aren't always predictive of human response, only use drugs in this category during pregnancy when the benefit outweighs the risk.

Acute sufferers

If a patient is in the acute phase of a seasonal allergic episode, consider an approach other than using a pure mast cell stabilizer, which is of limited value in these cases. For these patients, I use combinations of antihistamines and mast cell stabilizers. Although you can prescribe two different agents (lodoxamide and levocabastine HCl 0.05% [Livostin] or lodoxamide and emedastine difumarate 0.05% [Emadine]), it's often inconvenient for patients to use two medications four times per day.

Instead, use a single agent with both actions. Olopatadine HCl 0.1% (Patanol), ketotifen fumarate (Zaditor) or azelastine HCl 0.05% (Optivar) are effective choices for these patients.

All of these agents are prescribed in a b.i.d. dosage and are easy for patients to use. I usually re-evaluate patients with moderate to serious reactions 1 week after the initial visit.

Olopatadine, ketotifen and nedocromil are available in 5-ml bottles for 25 days of full therapy. The exception in this group is azelastine, which is available in a 6-ml bottle.

As a group, these agents are safe and effective for managing mild to moderate allergic conjunctivitis. The most common side effect patients experience is headache. Individual responses to these agents may vary, so you may need to go through some trial and error to find the agent that's most effective and free of adverse effects for a patient.

Contact lens wearers

The treatment of seasonal allergic conjunctivitis in the contact lens wearer presents special challenges. Although ophthalmic medications aren't typically approved for use with contact lenses, the contact lens wearing population is usually reluctant to return to spectacles.

I use a therapeutic approach for this special population that, in the strictest sense, is an off-label use, yet is effective and meets (at least in spirit) the recommendations for these medicines. I recommend that contact lens wearers suffering from seasonal allergic conjunctivitis instill 1 to 2 drops of an antihistamine/mast cell stabilizer when they wake up and wait at least 15 minutes before inserting their lenses.

I then advise patients to remove their lenses and instill their second dose for the day when they get home from work or school. This effective regimen allows the patient to continue wearing contact lenses even during the allergy season.

Adding steroids

Another approach to managing seasonal allergic conjunctivitis is using corticosteroids. One of the newer agents is loteprednol etabonate 0.2% (Alrex), which is approved for seasonal allergic conjunctivitis. It has a good safety profile for external disease and is rapidly metabolized with a low risk of elevating intraocular pressure.

As with all steroids, take care to avoid using loteprednol in the presence of herpetic infection. I use moderate to severe chemosis as an indication for steroids prescribed q.i.d. for 1 to 5 days. Loteprednol is available in both 5- or 10-ml bottles.

Managing papillary conjunctivitis

Another use for mast cell stabilizer agents for managing papillary conjunctivitis. The most common etiology for this condition is soft contact lenses, particularly those with an infrequent replacement cycle. The best treatment option for this condition is modifying both the contact lens replacement cycle and the patient's behavior.

The pharmacological management of papillary conjunctivitis often includes mast cell stabilizers. Lodoxamide, cromolyn sodium 4% (Crolom) or pemirolast are excellent choices. I prescribe these agents on a q.i.d. basis for as long as 2 months.

If the inflammation is significant, the patient will need quicker relief than mast cell stabilization therapy alone can achieve. In these cases, I prescribe a corticosteroid such as loteprednol etabonate 0.5% (Lotemax), rimexolone 1% (Vexol) or fluorometholone 0.1% (FML) q.i.d. 7 to 14 days along with the mast cell stabilizer. This combination hastens the recovery process and allows the patient to return to contact lens wear sooner and may reduce the treatment duration with the mast cell stabilizer.

Treating VKC

Vernal keratoconjunctivitis is another condition we treat in part with mast cell stabilizers. The population at risk for vernal disease is most often juvenile males who are thought to lack histaminase (the enzyme that breaks down histamine).

In addition to significant papillary changes, this condition is also characterized by limbal and corneal changes. Management of VKC usually includes steroids and mast cell stabilizers. Medical management is often continued for extended periods. Occasionally, tarsal conjunctival resection is necessary in those cases resistant to medical therapy.

An effective weapon

Mast cell stabilizers are valuable in the long-term control of many allergic conditions, and that's why they play a central role in treating seasonal allergic conjunctivitis, papillary conjunctivitis and VKC. These agents are safe and effective alone and when combined with an antihistamine, are still a safe treatment for allergic conjunctivitis. 

Dr. DiMartino is an assistant professor of Clinical Optometry at the University of California, Berkeley School of Optometry and is in group practice in Lafayette, Calif. He is also a fellow in the American Academy of Optometry.

Dr. Christensen has a partnership practice in Midwest City, Okla. He's a diplomate in the Cornea and Contact Lens Section of the American Academy of Optometry. He's also a member of National Academies of Practice.