Combination drops are first-line therapy for allergies

Ocular allergies

Combination drops are first-line therapy for allergies

by Jena Passut EyeWorld Staff Writer

Most practitioners agree that combination drops are the go-to therapy for SAC (pictured here) Source: Andrea Leonardi, M.D.


Many ocular allergy suffers first try to quash symptoms by self-medicating with over-the-counter drops, but different classes of medications, especially combination antihistamine/mast cell stabilizers, are quite effective treating the irritating condition, according to several practitioners who spoke to EyeWorld.

More than 90% of patients with ocular allergy symptoms are affected by either seasonal allergic conjunctivitis (SAC) or perennial allergic conjunctivitis (PAC), with swelling and itching being hallmark symptoms.

Drop therapies available today attempt to stave off allergic conjunctivitis by focusing on the characteristic mast cell degranulation that is associated with the condition. Mast cell stabilizers help prevent the release of numerous pro-allergy mediators, while antihistamines block histamine from binding at its receptors after it already has escaped from the mast cell, according to Mark B. Abelson, M.D., associate clinical professor of ophthalmology, Harvard Medical School, Boston.

There is tremendous overlap of symptoms with dry eye disease, Dr. Abelson said.

"Once your tear volume is decreased you have less of a diluent eyewash and barrier protection effect of the normal tears, and the epithelial surface breaks down and the junctional complexes between the cells fall apart," he said. E-cadherins and other keratins are broken down in a SAC patient's conjunctiva, which may explain why the epithelium in these patients is less able to protect against allergens, said Paul Gomes, M.S., vice president of allergy research, Ora, Andover, Mass., an independent ophthalmic drug and device development firm founded by Dr. Abelson. Both Mr. Gomes and Dr. Abelson have been heavily involved in developing combination therapies for allergy suffers, especially over the past 15 years, Dr. Abelson said.

"There have been studies [with] biopsies of conjunctival tissue of allergy patients out of season compared to normal patients that show a degradation or a decrease in those junctional proteins that keep the epithelium barrier tight," Mr. Gomes said. "We've also done studies for the most recent antihistamine to be approved to show that antihistamines have the ability to prevent degradation of those type of proteins. We are looking at other therapies to prevent that from happening."

Before drops, ophthalmologists have to manage more than just the eyes of the patient, according to Terrence P. O'Brien, M.D., Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami. "We have to approach the patient both from a systemic point of view and ocular point of view because the eyes are obviously connected to the rest of the body," he said. "Some doctors view this as a nuisance to handle, but the impact on quality of life is substantial."

SAC often is accompanied by rhinitis, or runny nose.

"Patients usually focus on the nasal symptoms, even though the eye symptoms can make them miserable, too," Andrea Leonardi, M.D., neurosciences department, ophthalmology unit, University of Padua, Italy, said. Many ophthalmologists like Drs. Abelson, O'Brien, and Leonardi agree that avoidance is a key first step, but when that's not enough, there are a number of drugs in a doctor's armamentarium, including antihistamines and mast cell stabilizers.

Dr. Leonardi said his first line of treatment is using double multiple-action drugs, which contain a single molecule with multiple effects.

Dual-action antihistamine/mast cell stabilizers available on the market now are effective in many patients, he said. "Antihistamines with mast cell stabilizing abilities, also known as dual-acting agents, inhibit mast cell degranulation. They have a pretty good safety profile and have been used for a number of years with stable side effects," Dr. Leonardi said. "Combination antihistamines and vasoconstrictors can be used for occasional symptoms and redness, but I think they are usually preserved and the patients tend to use them chronically, which may give them drug-induced conjunctivitis."

The latest combination drop, Bepreve (bepotastine besilate ophthalmic solution 1.5%, Ista Pharmaceuticals, Irvine, Calif.), was approved by the FDA in 2009 for the treatment of ocular itching associated with allergic conjunctivitis. Others include Patanol (olopatadine hydrochloride ophthalmic solution 0.1%, Alcon, Fort Worth, Texas) and Elestat (epinastine HCl ophthalmic solution 0.05%, Allergan, Irvine, Calif.).

Combination therapy drops are a "mainstay treatment," Dr. O'Brien said. "They not only provide rapid relief of the itch, but there is the mast cell stabilization that prevents a cascade of symptoms," he said, adding that he has SAC patients keep the drops "at the ready" before allergy season and has them administer the drops twice a day during that time.

Dr. Abelson suggesting having the patients store the eye drops in the refrigerator for added cooling effects.

Over-the-counter drops such as Claritin Eye (ketotifen, Schering-Plough, Kenilworth, N.J.), Zyrtec (ketotifen, McNeil Consumer Healthcare, Fort Washington, Pa.), and Zaditor (ketotifen fumarate ophthalmic solution, Novartis, Basel, Switzerland) are readily available for a quick fix, but don't always work.

Antihistamine drops alone aren't as effective either, Dr. Abelson said. "Regular antihistamines are very short acting and don't have any anti-inflammatory effects," he said. Patients also may use mast cell stabilizers alone. Those include sodium cromoglicate (various manufacturers), nedocromil (Alocril, Allergan), and lodoxamide (Alomide, Alcon), but the doctors agreed that they aren't as effective as combination drops.

"We do not have a really good mast cell stabilizer alone," Dr. Abelson said. "Cromolyn was never approved for SAC, contrary to people's thoughts, and it has fallen out of use," Dr. Abelson said. "Others are very weak and rarely used."

Dr. O'Brien agreed that combination therapy is the standard of care. "It is very rare that you want to separate those actions—the antihistamine and the mast cell stabilizer," Dr. O'Brien said.

"Drugs that reduce eosinophil activation such as lodoxamide and spaglumic acid and systemic antihistamines also can be used as a standard treatment," for severe forms of allergy such as vernal keratoconjunctivitis or atopic keratoconjunctivitis, Dr. Leonardi said.



Editors' note: Dr. Abelson is the founder of Ora. Mr. Gomes is vice president of allergy research at Ora. Dr. Leonardi has no financial interests related to this article. Dr. O'Brien is an ad-hoc, non-salaried consultant for Alcon, Allergan, and Bausch + Lomb (Rochester, N.Y.).

Contact information
Abelson: mbabelson@oraclinical.com
Gomes: p.gomes@oraclinical.com
Leonardi: andrea.leonardi@unipd.it
O'Brien: 561-515 1544, tobrien@med.miami.edu