Inflammatory cascade linked to allergic conjunctivitis

By understanding the inflammatory cascade that occurs during an allergic response, clinicians will be better equipped to choose effective medication for allergic conjunctivitis.

Key Points

By understanding the inflammatory cascade that occurs during an allergic response, clinicians will be better equipped to choose effective medication for allergic conjunctivitis. New drugs that inhibit multiple mediators of the inflammation response provide maximum relief while curbing unwanted systemic side effects. This treatment approach has additional benefits for dry eye and other related allergy symptoms.

Understanding of ocular surface problems and treatment has improved dramatically over the past 10 years, according to Bill G. Bell, MD, medical director of the Bell Eye Care Institute, Carlsbad, CA.

"Those of us who trained a few years ago used to dread seeing the itchy, burning, and watering eye because there was not much we could do about it," Dr. Bell said. "Yet, these are the most common symptoms we see. During seasonal allergies, these patients can't wear contact lenses, can't get out in the wind, and their vision gets more blurry."

"Steroids are the gold standard for stopping inflammation, but they also have the highest potential for adverse side effects," Dr. Bell said. "For example, if the oral corticosteroid you're taking produces measurable blood levels of steroid, we know without question your likelihood of inducing cataracts increases."

To a lesser degree, nasal corticosteroid sprays have been implicated in increased IOP and cataract risk. Topical medications incur the least side effects, and new pharmaceutical options make them more effective.

Cascade explained

In the June issue of Review of Ophthalmology, Dr. Bell and co-authors explained the inflammatory cascade, comparing the pharmaceutical properties of five currently available topical agents approved for allergic conjunctivitis. All five medications examined in the review article-azelastine HCl 0.05% (Optivar, MedPointe Pharmaceuticals), epinastine HCl 0.05% (Elestat, Inspire Pharmaceuticals and Allergan), ketotifen fumarate 0.25% (Zaditor, Novartis), olopatadine HCl 0.1% (Patanol, Alcon Laboratories), and olopatadine HCl 0.2% (Pataday, Alcon Laboratories)-stabilized mast cells and blocked histamines during the early phase of the inflammation response. During the later phase, however, two of the five achieved no mediation effect, and another two had limited effect. Azelastine alone inhibited and down-regulated four late-phase mediators: platelet activating factor, eosin-ophils, ICAM, and leukotriene.

The clinical goal, Dr. Bell said, is to block as many pathways to inflammation as possible, during both the early and late phase, while choosing medication with the fewest side effects.

"Based on the clinical and research data currently available about medications that combine antihistamine and mast cell stabilizing compounds, it appears that [azelastine] blocks more inflammation pathways," he added.

"All those products have good vehicles-the substance that the active ingredients are dissolved in," said John R. Favetta, MD, clinical instructor of ophthalmology, University of Medicine and Dentistry of New Jersey, Newark, who is among the co-authors of the June article. "Take as an example [azelastine]. Its formulation has some hydroxypropylmethylcellulose, or hypermellose. Hypermellose is an ocular lubricant that has been used on the surface of the eye to increase moisture content."

This effect becomes beneficial in treating allergic inflammation as well as dry eye symptoms.