rx perspective
Ocular Allergy: Upping the Ante
A higher concentration of olopatadine makes drops more effective and convenient -- with no apparent downside.
By Steven J. Lichtenstein, M.D.

Several recent clinical trials have focused on Patanol 0.2%, a new product currently under review by the FDA that contains olopatadine 0.2%. The elevated concentration (previously 0.1%), along with other changes in the formulation, should keep drug concentration level in the eye above the active threshold longer, as well as have the potential for more potent activity. Most important, the drop only needs to be used once a day.

A number of advantageous characteristics of olopatadine have been demonstrated in recent studies:

Significant reduction in ocular allergy symptoms. A double masked, randomized, placebo controlled study involving olopatadine 0.2%, conducted by Abelson et al, was presented at this year's WSAAI (Western Society of Allergy, Asthma & Immunology) meeting. Subjects challenged with specific allergens in the eye showed significant reductions in itching and redness when challenged 27 minutes after medication instillation, 16 hours after instillation, and -- for the first time ever with a topical anti-allergy drug -- when challenged 24 hours after instillation. Ocular itching scores (compared with placebo) were significantly reduced at all three time points.

A reduction in the release of mast-cell mediators. A study presented by Nichols et al. at ARVO demonstrated that olopatadine, instilled before undergoing a conjunctival allergen challenge, reduced the release of histamine, expression of ICAM (an adhesion molecule that draws in migrating cells such as eosinophils), and eosinophils, neutrophils and total cells. This reduction correlated with a significant decrease in clinical signs and symptoms.

Olopatadine's effect on human ocular mast cells is important, considering the heterogeneity of mast cells and their varying reactivity to drugs in different tissues and species.

A lack of disruptive effects on cell membranes. A study conducted by Graff et al., reported at ARVO, examined the effects of anti-allergic agents on cell membranes, including human corneal epithelial cells and conjunctival mast cells. Unlike desloratadine, clemastine, azelastine, ketotifen and epinastine, olopatadine showed minimal disruptive ac-tivity and no detrimental effect on cell membrane integrity. (This may explain why olopatadine causes less discomfort than many drugs. It may also mean greater long-term safety.)

A track record of being safe and well-tolerated. A 6-week study of 351 subjects conducted by Lichtenstein et al., reported at WSAAI, indicated that olopatadine 0.2% is safe and well-tolerated in adults and children as young as 3 years of age. Adverse events and ocular parameters showed no difference between olopatadine- and placebo-treated subjects.

More Power, More Convenience

The increase in concentration may prove beneficial in several ways:

• It may lead to a higher efficacy and responder rate.
• Enhanced mast-cell stabilization may mean broader applicability, such as achieving superior attenuation of allergic signs (i.e., lid swelling), and facilitating proper ocular wound healing.
• A more potent drop may have a greater effect on nasal symptoms and the potential for treating severe forms of allergy such as atopic or vernal keratoconjunctivitis.

Also, once-daily dosing will mean greater convenience for pa-tients, particularly those unable to use more frequent dosing regimens, such as contact lens wearers. Parents won't need to send medication to school with children, or carry a bottle to work; one dose in the morning will last all day. This will also help with compliance, which is crucial to mast-cell stabilization.

Steven J. Lichtenstein, M.D,. is a pediatric ophthalmologist in Louisville, Ky. He is the current chair of the American Academy of Pediatrics, Section on Ophthalmology.