Favorable profile makes azithromycin a rationale choice for anterior and posterior blepharitis

March 15, 2008

Azithromycin 1% ophthalmic solution (AzaSite, Inspire Pharmaceuticals) has many properties that make it a rational choice for the treatment of blepharitis. Evaluations conducted by two ophthalmologists yielded favorable results in showing azithromycin was safe, well-tolerated, and resulted in rapid and dramatic improvement of both anterior and posterior lid margin disease.

Key Points

Results from small studies undertaken by independent investigators indicate that azithromycin 1% ophthalmic solution (AzaSite, Inspire Pharmaceuticals) offers promise as a safe, well-tolerated, and rapidly effective therapy for anterior and posterior blepharitis.

Jodi Luchs, MD, explored the potential of azithromycin 1% as a treatment for blepharitis in an uncontrolled pilot study including 12 patients with posterior blepharitis and 12 patients with anterior lid margin disease. Patients with posterior blepharitis used the azithromycin twice daily, instilling it into the eye or onto the lid surface, while anterior blepharitis patients used the drop twice daily for 1 week and then decreased the dosing frequency to once daily. All patients were also instructed in lid hygiene procedures, including application of warm compresses plus use of lid scrubs by the anterior blepharitis patients.

When evaluated 2 weeks after starting azithromycin, all anterior blepharitis patients demonstrated resolution of crusting and collarettes along with significant reduction in lid margin inflammation and improvement in subjective symptoms. Ten of the 12 posterior blepharitis patients demonstrated reduced lid margin erythema and improvement in the appearance of the meibomian orifices and/or meibomian gland secretions. Especially noteworthy was the fact that most of the 10 responders in the posterior blepharitis group reported onset of benefits after just 1 week of starting treatment, said Dr. Luchs, director, department of refractive surgery, North Shore/Long Island Jewish Health System, Manhasset, NY, and assistant clinical professor of ophthalmology and visual sciences, Albert Einstein College of Medicine, Bronx, NY.

The efficacy of azithromycin for treating both anterior and posterior blepharitis may be attributed to multiple features of this agent, including a dual mechanism of action; azithromycin has both antimicrobial and anti-inflammatory properties, as well as excellent penetration into target tissues.

"There are data to show that azithromycin has anti-inflammatory activity independent of its antimicrobial effects and also documenting that it achieves high concentrations in the cornea, conjunctiva, and lid after topical administration of just a single drop. The latter feature relates to both an intrinsic property of the molecule and the DuraSite drug delivery system used to formulate AzaSite that enhances drug tissue penetration by prolonging drug delivery," explained Dr. Luchs.

He noted that the efficacy of azithromycin in treating anterior blepharitis was anticipated considering azithromycin provides good coverage against staphylococcal bacteria implicated in the pathogenesis of this form of lid margin disease. The rapid and significant improvement achieved by patients with posterior blepharitis was more unexpected when considered relative to the responses achieved with other commonly used treatments for posterior blepharitis. For example, it can take 6 weeks or longer for patients to respond to anti-inflammatory treatment with oral doxycycline whereas management with lid hygiene measures alone is unlikely to afford such dramatic symptomatic and objective improvement, especially after just a few weeks of therapy, noted Dr. Luchs.

"On the other hand, the efficacy of azithromycin in treating posterior blepharitis is not that surprising if one takes into account its anti-inflammatory activity and tissue penetration properties," Dr. Luchs said.

Treatment with azithromycin was also very well-tolerated. One patient with anterior blepharitis stopped azithromycin prematurely due to stinging upon instillation, but even that patient reported symptomatic improvement and had clinical resolution of the lid margin findings. Of the two posterior blepharitis patients who did not respond adequately to azithromycin, one discontinued treatment because of stinging. No other adverse events were noted.

"Anterior blepharitis will respond to treatment with ophthalmic antibiotic ointments, such as bacitracin or erythromycin. However, these ointment preparations tend to have poor patient acceptance because they result in lid gumming and blurred vision. Systemic side effects can also be an issue with oral doxycycline that may be prescribed for patients with posterior blepharitis. Compared with these alternate regimens, azithromycin 1% ophthalmic solution is safer and better tolerated," noted Dr. Luchs.

He added that the ability of the DuraSite vehicle to coat the ocular surface is an added benefit of using azithromycin 1% considering that tear film dysfunction and ocular surface damage are common comorbid findings in patients with posterior blepharitis.

"A close relative of the DuraSite vehicle was previously marketed as an artificial tear. In addition to improving retention of the active ingredient on the ocular surface, this vehicle provides good ocular surface lubrication and helps to relieve dry eye symptoms that blepharitis patients may suffer as a result of an unstable tear film," said Dr. Luchs.

Dr. Luchs has just launched a controlled trial investigating azithromycin 1% for the treatment of posterior blepharitis in which patients are being randomized to lid massage alone or combined with azithromycin. A protocol for a controlled trial evaluating the efficacy and safety of azithromycin 1% for the treatment of anterior blepharitis is under development.