Match the ocular allergy treatment to the patient, the symptoms

Issue: April 1999

As symptoms differ widely among the 23 million ocular allergy sufferers in the United States, doctors are challenged to choose appropriate therapies to provide relief. These choices are based on efficacy, safety, convenience of dosing and comfort of administration for the patient. The objectives of treatment include decreased inflammation, minimal dosing, ease of compliance, minimum side effects and increased tolerance to allergy triggers.

The most common complaint among ocular allergy sufferers, practitioners agree, is itchy, watery eyes. Ocular allergic reactions cause mast cells to release mediators, including histamine, which creates the symptoms of allergic ophthalmologic problems. “But the main thing with this is it is not only a histamine phenomenon,” said Dennis L. Spangler, MD, at the American Academy of Ophthalmology meeting. “It also is a chronic inflammation phenomenon. As the allergic reaction continues, there is infiltration of the eye by the cells of chronic inflammation, including eosinophilia and lymphocytes, that contribute to a hyper-irritability state that occurs not only in the lung and the nose, but also in the eye.”

Dr. Spangler, associate clinical professor at the Medical College of Atlanta and chief medical officer at the Atlanta Allergy and Asthma Clinic, added that if you want to control the allergic symptom process both acute and chronic inflammation must be addressed. Inflammation is often overlooked. When patients have nasal stuffiness and asthma, the ophthalmologic symptoms are often just as significant and chronic, but might not be mentioned, according to Dr. Spangler. “They have a tendency to overlook that symptomatology,” Dr. Spangler said. “It’s important to ask about these symptoms.”

Other symptoms include lid swelling, redness, hyperemia, chemosis, eyelid edema and significant mucous discharge.

Treatments for mild symptoms

Approaches to ocular allergy management differ as symptoms vary. For very mild symptoms, a cold compress can be effective in relieving itching, said Valarie Conrad, OD, an associate professor at the Illinois College of Optometry.

“The relief is brief, but if the symptoms are mild and sporadic, that may be all you need. If it seems more involved than that, you look into ocular medications,” she said.

“First is the obvious, is the easiest, is the cheapest and has the least amount of problems — tears,” Dr. Spangler said. “They provide a washing agent and increase the barrier, but they have a limited benefit.”

“Many doctors forget about artificial tears as a means of helping in the realm of ocular allergies,” said Charles B. Slonim, MD, FACS, associate clinical professor of ophthalmology at the University of South Florida College of Medicine in Tampa, Fla., and private practitioner in Tampa. “Artificial tears are an important part of ocular allergy treatment, mainly because you get pollen stuck on the tear film and a portion of the artificial tears is literally washing these potential allergens off the surface of the eye.”

Artificial tears must be used frequently by patients to be effective; however, if the patient is symptomatic, this may not be the best treatment choice. Artificial tears can help wash out or dilute antigens, but the underlying causes will remain, Dr. Conrad said.

“I prefer to go with a vasoconstrictor and antihistamine combination product for mild symptoms, such as Naphcon-A (pheniramine maleate 0.3%, naphazoline HCl 0.025%, Alcon), because then I’m really getting at the root of the problem, as opposed to giving just very brief comfort as I would with an artificial tear,” Dr. Conrad said.

Other vasoconstrictor and antihistamine combination products now available over the counter include OcuHist (pheniramine maleate, naphazoline HCl, Pfizer) and Opcon-A (naphazoline HCl, pheniramine maleate, Bausch & Lomb). Dr. Slonim tends to use these frequently.

“Patients love them,” Dr. Slonim said. “Naphcon-A, Opcon-A and OcuHist were prescription drugs until about 2 or 3 years ago, and the Food and Drug Administration let them go over the counter, which was the greatest thing for me and my staff.” Dr. Slonim mentioned that in his patients who have used vasoconstrictors for long periods of time, there has been no ill effect.

Rebound effects

However, some doctors have complained that these products are associated with rebound effects. The vasoconstrictors constrict blood vessels, and patients tend to get hooked on these types of products. They make the eye white temporarily. “I tend not to use the vasoconstrictors, because I don’t like them,” said Michael B. Raizman, MD, from the New England Eye Center. “I don’t think they address the underlying problems. They can lead to major problems, such as rebound hyperemia, if they are used for a long time.”

According to Dr. Raizman, the antihistamine in these combination products is extremely weak. If patients have pure itching and no other symptoms, Dr. Raizman usually gives them an antihistamine. If patients have burning and irritation, Dr. Raizman usually uses a topical nonsteroidal anti-inflammatory.

“Some antihistamines and decongestants work in the eye, and I would say most people tend to use something with a vasoconstrictor or decongestant and an antihistamine combined,” said allergist Ira Finegold, MD. “That was the tradition until about a year ago.”

According to Dr. Finegold, the introduction of Patanol (olopatadine HCl ophthalmic solution, Alcon), a drug with combined antihistamine and mast cell stabilizer properties, hit the market and has been quite effective. Dr. Finegold reports that, in the past, physicians were instructed to start with a less potent drug and gradually work their way up. “Now, you can come in, hit it hard and avoid the whole [allergic response],” Dr. Finegold said.

Antihistamines

For patients with more acute symptomatology, antihistamines may provide faster relief, said Gary E. Oliver, OD, from TLC The Laser Center in Plymouth Meeting, Pa. If these symptoms do not appear likely to continue through the complete allergy season, they would likely benefit from an antihistamine drop, such as Livostin (levocabastine, Ciba Vision) or Emadine (emedastine, Alcon).

“A patient who is exposed to an antigen for the first time may not have a lot of tissue changes in the conjunctiva but may have itching related to free histamine in the tear film. Many of those patients will get quicker relief from an antihistamine drop,” Dr. Oliver said.

Though prescribed for use two to four times daily, patients can usually use the drops as needed, he said.

After using vasoconstrictors as a first line of treatment, Dr. Slonim said he may turn to antihistamines such as Livostin, Emadine and Patanol. “I think Patanol is a good antihistamine, but I’m not impressed by its mast-cell stabilizing properties,” Dr. Slonim said. “In my 17 years of practice, I have used tons of cromolyn.”

Cromolyn sodium is the active chemical in Crolom (cromolyn sodium, Bausch & Lomb) and Opticrom (cromolyn sodium, Allergan).

Dr. Slonim added that Patanol is a good antihistamine, but a problem lies in the dosage of the drug, which is one to two drops a day, twice a day, 6 to 8 hours apart. “If you use it only twice a day as it is detailed by the sales reps, you don’t keep a therapeutic level because patients go into the trough level overnight,” Dr. Slonim said. He added that practitioners and patients will find that when Patanol is used three times a day, it will work better. Dr. Slonim said that he tends to use an over-the-counter antihistamine/decongestant and will add the prescription mast-cell stabilizer Crolom as his first- and second-line drugs.

On the other hand, Dr. Oliver is more impressed with Patanol’s effectiveness as a mast-cell stabilizer than its antihistamine properties. “While it has strong antihistamine properties, I’m not sure those properties are as strong as a straight antihistamine such as emedastine,” he said.

He prefers Patanol for its role in stopping the mechanisms that cause much of the discomfort associated with ocular allergies. “It stops the mast-cell degranulation process, which is the major part of the seasonal ocular allergy mechanism, and it is clearly the drug of choice for patients who have seasonal problems that last for weeks or months,” Dr. Oliver said.

“The other benefit of olopatadine is that it is one of two mast-cell stabilizing drugs that also have a strong impact on preventing eosinophil migration and breakdown of eosinophils. When eosinophils break down, they release a substance called the major basic protein, which is a major cause of some of the tissue irritation that you get in chronic seasonal allergies,” Dr. Oliver said.

Topical steroids

The newer allergy drugs have replaced the use of topical steroids to some degree, according to Dr. Finegold. “We tend not to use topical steroids in the eye because, if it turns out as a misdiagnosis and it is a viral disease, steroids tend to make the virus worse,” Dr. Finegold said. “With topical steroids, you do have certain side effects.”

Dr. Finegold added that when it seems a topical corticosteroid is needed the patient should be referred for a second or third opinion. He said that with a drug such as Patanol, doctors seldom have to follow that route any longer.

Topical steroids are still helpful when a primary therapy to treat the allergy does not work, Dr. Oliver said. He recommends prescribing steroids in a pulse fashion concurrently with the primary therapy. The steroid is used at a high dosage to start, then is rapidly tapered off after a few days, while the maintenance treatment drug is continued.

“The reason you are prescribing them in that manner is that you are using the steroid to quickly suppress the immune response to allow the other maintenance drugs — the antihistamine or mast-cell stabilizer — to work,” Dr. Oliver said.

Systemic antihistamines

When topical therapies fail to treat the ocular symptoms, practitioners should consider prescribing systemic antihistamines to treat the underlying cause, Dr. Oliver said. If the patient is experiencing deep tissue changes associated with the allergy, such as blepharoconjunctivitis with swelling of the eyelids, particularly in the morning, topical drops will not help.

The doctor should use a slit lamp to evaluate the meibomian glands and assess the bulbar and palpebral conjunctiva, said David W. Hansen, OD, in private practice in Des Moines, Iowa.

“When we have severe seasonal allergy, we will get what is known as a Mag sign, when you externally pull down the lower lid and see a proptosis or bulging out of the inferior palpebral conjunctiva. It doesn’t have to be hyperemic; it can be mildly injected or inflamed. Then you know you are dealing with a seasonal ocular allergy,” Dr. Hansen said.

The systemic antihistamines Dr. Hansen recommends include Allegra (fexofenadine HCl, Hoechst Marion Roussel), Zyrtec (cetirizine HCl, Pfizer), Claritin (loratadine, Schering) and Hycomine (phenylpropanolamine, hydrocodone, DuPont).

Another reason to prescribe a systemic antihistamine is if there are other related medical findings, such as rhinitis, otitis media or upper respiratory problems.

“Patients who have associated systemic symptoms and clinical ocular disease are going to be better served by being on a systemic antihistamine and then using the topical therapy as a supplement,” Dr. Oliver said.

Nonsteroidal anti-inflammatories

Acular (ketorolac tromethamine, Allergan) is the only nonsteroidal with an ocular allergy indication for seasonal allergic conjunctivitis. According to Dr. Slonim, patients frequently complain about this product because of the burn level, which has led him to not prescribe it. He added that Acular only works on the cyclooxygenase arm of allergic reactions and not the lipoxygenase pathway. This would prevent the production of prostaglandins but would not prevent the production of leukotrienes, which also are potent inflammatory chemical mediators, according to Dr. Slonim. “Acular only affects one area of the inflammatory chain; therefore, why bother unless you are going to get both arms,” he said.

According to Dr. Slonim, research is underway to find a nonsteroidal anti-inflammatory drug that works specifically on both the cyclooxygenase and lipoxygenase pathways. Other research includes cyclosporine being used for allergies.

Dr. Slonim mentioned that he uses more topical steroids for treating both acute and chronic seasonal allergic conjunctivitis. “I use Alrex (loteprednol etabonate, Bausch & Lomb) because of its efficacy in treating the signs and symptoms of seasonal allergic conjunctivitis, but mainly because of its safety profile,” Dr. Slonim said. “Relief from itching and redness occurs in less than 1 hour.”

Dr. Slonim said that many eye care practitioners are steroid shy when it comes to treating external ocular inflammatory processes, especially seasonal allergic conjunctivitis. He had similar concerns about topical steroids until he started administering Alrex. “I appreciate Alrex’s safety profile, which has made me less steroid shy in using topical steroids as a first-line drug for ocular allergic reactions. In Florida, we have 12 months of seasonal allergies; therefore, seasonal allergic conjunctivitis is a year-round problem in my practice,” he said.

Dr. Raizman noted that all of the topical nonsteroidal and antihistamine drops can cause irritation in certain patients, but these drops are extremely safe and the irritation is short-lived. “If patients are reassured that no harm is caused by the drops, they usually do not have any problem using them,” Dr. Raizman said. “Topical nonsteroidal drops work not only to reduce inflammatory mediators but also to directly inhibit pain responses. They are a very effective pain killer on the ocular surface.”

For Your Information:

Dennis L. Spangler, MD, can be reached at Atlanta Allergy and Asthma Clinic, Atlanta, GA 6667 Vernon Woods Dr., Suite A-3, Atlanta, GA 30328; (404) 252-4207; fax: (404) 303-2758. Dr. Spangler has no direct financial interest in the products mentioned in this article. He is a member of Alcon’s Speaker’s Bureau.

Valarie Conrad, OD, can be reached at at the Illinois College of Optometry, 3241 S. Michigan Ave., Chicago, IL 60616; (312) 949-7304; fax: (312) 949-7660. Dr. Conrad has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.

Charles B. Slonim, MD, FACS, can be reached at 4444 E. Fletcher Ave., Ste. D, Tampa, FL 33613; (813) 971-3846; fax: (813) 977-2611. Dr. Slonim has no direct financial interest in the products mentioned in this article. He is a paid consultant for Bausch & Lomb Pharmaceuticals.

Michael B. Raizman, MD, can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Boston, MA 02111; (617) 636-7625; fax: (617) 636-4866. Dr. Raizman has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Ira Finegold, MD, can be reached at 121 E. 60th St., New York, NY 10022; (212) 758-4633; fax: (914) 722-9175. Dr. Finegold has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Gary E. Oliver, OD, can be contacted at TLC The Laser Center at 600 W. Germantown Pike, Ste. 160, Plymouth Meeting, PA 19462; (610) 940-3937; fax: (610) 940-9566. Dr. Oliver has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

David W. Hansen, OD, can be reached at 2600 Grand Ave., Ste. 202, Des Moines, IA 50312; (515) 243-1667; fax: (515) 243-3604. Dr. Hansen has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.