CONTINUING EDUCATION

Making an Impact On Allergies

A combination antihistamine and mast cell stabilizer offers immediate and long-term action.

By Laurie Sorrenson, O.D., F.A.A.O.

The 2003-2004 Gallup Study of Allergy reports that as many as 50% of the U.S. population is affected by allergies. Of these, 83% suffer ocular symptoms. This translates to about 120 million Americans with ocular allergies, and in the spring, it feels like all of them are coming to see us.

Most allergic conjunctivitis cases are seasonal (SAC) or perennial (PAC), and treatment for both types should be directed at the underlying etiology of the disease. As I'll discuss here, studies show that a dual-action, daily-dose medication that combines an antihistamine and a mast cell stabilizer is a safe, effective and convenient option.

Behind the itch

Itching is the hallmark sign of SAC or PAC. Your patients' eyelids are swollen, and their eyes are red, chemotic and watery. Scrapings show elevated eosinophils. Whether the problem is seasonal (pollens) or perennial (dust mites, animal dander and mold), your patients' allergies are causing ocular surface inflammation and maddening discomfort.

Ocular allergies result in swollen eyelids and red, chemotic watery eyes.

The allergic reaction is triggered by antigens, which cross-link with the immunoglobulin E antibody (IgE) on the mast cells, leading to mast cell degranulation. This, in turn, releases histamines and proinflammatory mediators, such as prostaglandins, tryptase and heparin. The histamine quickly binds with H1 receptor sites on the nerves and causes itching. It also binds to H1 receptor sites on the blood vessels, causing redness, chemosis and fluid leakage. The proinflammatory mediators only add to the redness and swelling, and there's no end in sight, because antigens continue to bombard the eyes as part of the inflammatory cascade.

Dual effects

If we follow the etiology of allergic conjunctivitis, we can discern some important information. With 50 million mast cells in the human conjunctiva, the mast cell is central to the ocular allergic response. Allergies cause mast cell degranulation and the release of histamines and proinflammatory mediators. Therefore, the most effective medications will address both problems and will rapidly relieve symptoms.

Antigens that cross-link with the IgE antibody on the mast cells trigger the allergic response. This leads to mast cell degranulation and the release of histamines and proinflammatory mediators.

An antihistamine's mechanism of action is simple. It's attracted to the same H1 receptor sites that histamine seeks. It binds to those sites, effectively blocking the attachment of histamines and preventing itching and redness. Clearly, it's beneficial to put an antihistamine to work early in the inflammatory process.

We also need to use a mast cell stabilizer to effectively treat ocular allergy. These drugs prevent recurrence of the allergic response by inhibiting the release of proinflammatory mediators.

Study results

The most commonly prescribed drugs for ocular allergies are olopatadine 0.1% (Patanol, Alcon), olopatadine 0.2% (Pataday, Alcon), epinastine (Elestat, Allergan), ketotifen fumarate (Zaditor, Novartis Ophthalmics) and azelastine (Optivar, Meda Pharmaceuticals Inc.).

Olopatadine 0.1% is the market leader because studies have shown it's clinically effective as a specific H1 antagonist and mast cell stabilizer. It has a quick onset of action, and it's been shown to be comfortable and safe for patients.^1–11

In a conjunctival allergen challenge (CAC) study, which compared olopatadine 0.1% to azelastine⁵ and epinastine¹¹, mean itching scores at 5 minutes were better for olopatadine with statistical significance. The drug also performed better in ocular redness at onset and 10, 15 and 20 minutes post-challenge. Another study showed that olopatadine was significantly more comfortable in the eye than azelastine.⁶

While results are satisfying, another factor has driven the development of another olopatadine formulation: olopatadine 0.2%. Some studies show overall improvements in adherence, patient quality of life, patient satisfaction and cost when patients can dose less frequently.¹² What's more, 95% of allergy patients say that a long-lasting allergy medication is important, so they may be more satisfied if they can use fewer drops.¹³

A once-a-day drug like olopatadine 0.2% could improve compliance over olopatadine 0.1%, and increased compliance through daily dosing has been shown to give patients better symptom control.¹² In an in vitro animal comparison of the two concentrations, olopatadine 0.1% lasted 14 to 15 hours, compared to 24 hours for olopatadine 0.2%.¹⁴

Newest option

Indicated for the treatment of ocular itching associated with allergic conjunctivitis, olopatadine 0.2% has the same safety profile as olopatadine 0.1%. Olopatadine 0.2% has an increased concentration and longer duration, which is why patients need to use it only once a day.^15,16

An antihistamine is attracted to the same H1 receptor sites that histamine seeks. It binds to those sites, effectively blocking the attachment of histamines, thereby preventing ocular itching and redness.

During in vitro studies, both doses of olopatadine thwarted the biphasic process that degranulates mast cells and releases mediators, while epinastine, azelastine and ketotifen did not.^17,18

In more than 10 clinical trials, more than 1,000 patients have been exposed to olopatadine 0.2%. In a randomized, double-masked, placebo-controlled CAC trial¹⁹ that studied 45 people with a history of allergic conjunctivitis, researchers checked patients for itching and redness at onset and after 24 hours. They found that olopatadine 0.2% significantly reduced ocular itching compared to placebo. In the same study, researchers also found a beneficial effect on conjunctival redness.

A multicenter, 10-week study²⁰ looked at the efficacy of olopatadine 0.2% against itching in 260 patients who were sensitive to grass pollen and experienced redness and tearing. They received 1 drop in each eye, once a day. In weekly assessments, patients rated olopatadine 0.2% significantly better than placebo in itching frequency. What's more, the results improved over time as the mast cell stabilizer had time to take effect. Ocular redness fared better than placebo in the same 10-week period.

In addition, the environmental study showed that 0.2% olopatadine was effective, even as allergen levels fluctuated from low to moderate.²⁰

In comparative drug studies, olopatadine 0.2% has continued to fare well. In the double-blind CAC trial²¹ against epinastine, 92 patients underwent screening, confirmation and an office visit.

Results showed that olopatadine 0.2% reduced itching and redness more effectively than epinastine and also scored well in the comfort comparison index.

Getting an edge

Should you choose olopatadine 0.2% over the 0.1% formulation? I'm beginning to do so because dosing matters. In a 4-week, multicenter trial,¹⁴ researchers evaluated 330 patients with a history of allergic conjunctivitis who were taking olopatadine 0.1% and felt satisfied. Some patients were switched to once-daily olopatadine 0.2%. Scores showed that patient satisfaction increased significantly among olopatadine 0.2% users. In their perception, olopatadine 0.2% was comfortable in the eyes (93%) and allowed them to wear contact lenses as desired (87.5%).

We want to be sure that we provide the most effective therapy. We want an antihistaminic effect because the patient feels it immediately. And we want mast cell stabilizing activity to prevent a recurrence of mast cell degranulation. In olopatadine 0.2%, we have a robust option for achieving both of those goals. OM

Dr. Sorrenson is in a group practice in Austin, Texas. She's a part-time faculty member at the University of Houston College of Optometry.