Future treatments for allergy may get away from steroids

Future ocular allergy treatments may include cyclosporine A, leukotriene receptor antagonist, customized medications and cell manipulation.

In the search for safe alternatives to steroid management of allergic diseases, physicians are turning to cyclosporine A and leukotriene receptor antagonists, two drugs with applications in other fields of medicine. Additionally, investigations are under way for future treatments, without steroids, that reach beyond pharmaceutical agents to include biological and environmental factors.

“The dangers of steroid are so great. The challenge has been to try to manage atopic and vernal keratoconjunctivitis with the minimal amount of steroid. Unfortunately, steroid is almost certainly necessary,” Roger J. Buckley, MA, FRCS, FRCOphth, said recently in an interview with Ocular Surgery News.

For years, steroids have been the first choice for serious allergic diseases that affect the cornea.

“However, the side effects of steroids can be vision-threatening, including viral infection, a rise in IOP, glaucoma and acceleration of cataract,” Dr. Buckley said.

Stefano Bonini, MD, of Rome, agreed.

“Studies have shown approximately 2% of patients with steroid treatment develop steroid-induced glaucoma. Whenever possible, only a brief course of steroid should be applied,” he said.

To minimize steroid use, doctors often prescribe mast cell stabilizers and antihistamines to treat allergic conditions. However, none of these therapies are as effective as steroids. As a result, doctors are eagerly looking ahead to safer, gentler treatments that effectively treat vernal keratoconjunctivitis and atopic keratoconjunctivitis without the side effects of steroids.

Immunotherapy in the eye

One treatment currently under investigation for allergy is cyclosporine A.

Cyclosporine A is an immunosuppressant that inactivates T-cell lymphocytes. These cells are involved in the body’s defense system. Doctors have found that the drug works “remarkably well” in the eye, Dr. Bonini said, and the drug is prescribed when steroids cannot be taken for medical reasons, or “just because steroids are not safe.”

“The drug is in clinical trials in treatment for conjunctivitis. In the past, cyclosporine A has been used to manage the rejection of transplant organs,” Dr. Buckley said. “It has been used a great deal in other fields. It’s effective and safe for suppressing the entire body’s immune system.”

To suppress only the eye’s immune system, the drug is applied topically to the ocular surface.

Cyclosporine A is currently under investigation for ocular diseases, and is not yet commercially available. If physicians want to use cyclosporine for this indication, the medication must be prepared in the clinic. It is dissolved in oil because it is insoluble in water, Dr. Buckley said. The medication is then administered via eye drops or an ointment.

Unfortunately, oily treatments in the eye are often difficult for patients to tolerate. However, if patients can tolerate this current form of the drug, it is to their advantage.

“It’s really quite remarkable. To some extent, cyclosporine A has revolutionized the treatment of these very two difficult conditions,” Dr. Buckley said.

Leukotriene receptor antagonists

Another medication attracting much interest for treating vernal and atopic keratoconjunctivitis is montelukast.

Like cyclosporine A, leukotriene receptor antagonists are not yet commercially available as topical eye medications. Dr. Bonini is currently conducting studies on one such drug.

“Montelukast is a lukotriene receptor antagonist. It seems the drug tries to block or prevent the activity of leukotriene mediators in the eye, to improve the signs and symptoms of allergic disease,” he said.

A series of leukotriene receptor antagonist drugs have become staple treatments for asthma in recent years. After the discovery of their effectiveness, doctors began applying leukotriene receptor antagonists systematically to benefit the eye, Dr. Bonini said.

Dr. Buckley said he believes using this drug on the eye “makes good sense.”

“I haven’t used it yet, but I’d like to,” he said.

Customized treatments

Dr. Buckley and colleagues are currently working on another form of steroid alternative that focuses on customized treatments. He is studying samples of human tissue and growing conjunctiva in culture to identify what inflammatory mediators are being produced in these cells.

“In the future we may be able to design individual treatments tailored for individual patients. We’ve done quite a lot of work and we hope to apply this knowledge in the future to design specific treatments,” he said.

According to Virginia Calder, BSc, PhD, a colleague working with Dr. Buckley at the London Institute of Ophthalmology, specific treatments in the future may include a greater understanding of genetics and environmental contributors.

“There are studies to show that regional differences throughout the world, different climates, different pollens and other allergens produce variations of conjunctivitis. Genetics, as well, may influence how each individual person responds to these various allergens,” she said.

Dr. Calder believes that in the future, when it comes to customizing treatment for the individual, these factors will play an important role in what medications are used.

“There are so many subtle differences involved. It is something that will take intensive research,” she added.

Cell manipulation

Another aspect of allergy management currently under investigation is the manipulation of T-cell lymphocyte cells. According to Dr. Bonini, there are two classes of T-cell lymphocytes: Th1 and Th2. Th1 is involved in infections, while Th2 is active in allergic diseases.

“In the future, if we are able to manipulate this response and switch from Th2 to Th1, we could improve the allergic condition,” he added.

Dr. Bonini said there are many approaches to this form of treatment. Currently, hormones and androgens can modify the response, but not enough clinical research has been done to really evaluate the ramifications.

“It’s under investigation, but I believe it could play a major role in allergy prevention,” he said.

For Your Information

• Roger J. Buckley, MA, FRCS, FRCOphth, can be reached at Moorfields Eye Hospital, 162 City Road, London, UK, EC1V2PD; +(44) 20-7493-0372; fax: +(44) 20-7935-5429; e-mail: RJBcity@aol.com.
• Virginia Calder, BSc, PhD, can be reached at the Institute of Ophthalmology, UCL, 11-43 Bath Street, London, UK, EC1V9EL; +(44) 20-7608-6848; fax: +(44) 20-7608-6954; e-mail v.calder@ucl.ac.uk.
• Stefano Bonini, MD, can be reached at Department of Ophthalmology, University of Rome, Tor Vergata; +(39) 06-350-3416; fax: +(39) 06 301-7436; e-mail: sbonini@mclink.it.