THERAPEUTIC INSIGHTS

Treat Lid Margin Disease

Topical antibiotic offers proven efficacy, high viscosity and may improve drug compliance.

Paul M. Karpecki, O.D., Cincinnati, Ohio

A recent addition to the antibiotic market should help in treating both Lid Margin Disease (LMD) and Conjunctivitis. LMD is a common, chronic disease, which often goes undiagnosed and is characterized by inflammation and often infection of the eyelids. Clinicians usually classify LMD as either anterior blepharitis or posterior blepharitis, also called Meibomian Gland Dysfunction (MGD). Anterior blepharitis affects predominantly the lid region around the lashes and is defined as inflammation associated with excessive colonization in this region. The most common bacteria associated with anterior blepharitis are Staphylococcus aureus and Staphylococcus epidermidis. Anterior blepharitis usually presents with scaling, debris and lid crusting. Posterior blepharitis involves the lid posterior to the lashes and results from disorders of the meibomian gland, such as inspissation. MGD presents with inflammation and a thickening of the posterior lid margin. Many MGD patients also have dry-eye disease due to the change in lipids secreted by the meibomian gland.

Conjunctivitis, whether due to bacteria, viruses or allergies, is also a common clinical complaint. Most cases of acute bacterial conjunctivitis result from some change in the host's defenses, such as disruption of the corneal epithelial layer. This allows normal flora found on the surface tissues or in the ocular adnexa to overgrow.¹ The most common of these types of pathogens are strains of Streptococci, Staphylococci or Corynebacterium.² Inoculation of the eye with external pathogens by a contaminated finger is also common.

Azasite may improve drug compliance in patients who have bacterial conjunctivitis.

Bacterial conjunctivitis is particularly prevalent in infants, school-aged children and the elderly, though you can encounter it in patients of any age. You can often differentiate the acute on-set of bacterial conjunctivitis from other etiologies, such as blepharoconjunctivitis, as it has a characteristic purulent or muco-purulent discharge not associated with a history of allergies or recent exposure to a potential toxin. (Therapy, however, may be reasonable if signs remain mild to moderate.)

Here are the four reasons azithromycin 1% ophthalmic solution (Azasite, Inspire Pharmaceuticals) is part of my antibiotic armamentarium.

1. Proven efficacy

The Food and Drug Administration (FDA) approved azithromycin 1% ophthalmic solution in April, 2007 for the treatment of bacterial conjunctivitis caused by Haemophilus influenzae, Streptococcus mitis group, Streptococcus pneumoniae, Staphylococcus aureus and CDC coryneform group G. The FDA granted approval of 1% azithromycin based on a series of clinical trials with placebo and active controls. In a phase III double-blind study, researchers randomized 743 adults and children older than age one who had bacterial conjunctivitis at 47 sites to 1% azithromycin or to 0.3% tobramycin (Tobrex, Alcon).³

Both groups received drops q.i.d. for five days. Those in the 1% azithromycin group received therapy b.i.d. on days one and two and followed by q.d. dosing on days three to five.

The researchers evaluated efficacy and safety at two follow-up visits. The 1% azithromycin and 0.3% tobramycin achieved nearly identical rates of clinical and bacteriological eradication.³ The researchers also observed a similarity in efficacy when they compared eradication rates for all gram-positive or all gram-negative pathogens and in comparing bacteriologic cure rates for the most common pathogens, such as S. aureus or H. Influenzae.

Both therapies were well tolerated. The most common side effects for azithromycin, occurring in less than 2% of patients, were eye irritation and conjunctival hyperemia.

2. Prolonged concentration

Azithromycin 1% has demonstrated prolonged high levels in drug-targeted ocular tissue.⁴ In its topical formulation, the vehicle DuraSite, a combination of polycarbophil, edetate disodium and sodium chloride, provides gel-forming particles that enlarge in the aqueous environment, increasing the viscosity and extending exposure of ocular tissues to the antibiotic. The viscosity of the formulation resists washout by tears, increasing the likelihood of bactericidal drug concentrations.

In addition, the viscosity of 1% azithromycin may provide relief for the dry eye that commonly accompanies bacterial conjunctivitis. I've noticed this anecdotally. Further, in the phase III studies, 94% achieved symptom relief by day three.^1,5

3. Anti-inflammatory effects

Research has shown oral azithromycin 1% to have significant anti-inflammatory and immuno-modulatory effects, as demonstrated by reductions in inflammatory cell infiltration, edema, mucus hypersecretion and expression of pro-inflammatory cytokines. The anti-inflammatory activity is much higher in cells exposed to bacterial products than in normal cells. The advantage in blepharitis: It exerts anti-inflammatory activity along with antibacterial activity.^6-9

4. Improved compliance

Azithromycin 1% may improve compliance, enabling the quick eradication of bacterial conjunctivitis, as it has a dosing schedule of one drop twice per day for the first two days, followed by one drop daily for the following five days. Nine drops is the total number per treatment course. The traditional dosing schedule for topical antibiotic treatment of bacterial conjunctivitis is four drops per day for five-to-seven days.

I've found that my adult patients comply with this treatment schedule because they appreciate the convenience of instilling less drops. Also, caregivers of young children who have bacterial conjunctivitis have cited this as a particular advantage, as this population is often uncooperative with drops, due to the discomfort of instillation.

Because 1% azithromycin helps LMD patients, is clinically effective in eradicating bacterial conjunctivitis, has a high viscosity and offers a dosing schedule that has improved drug compliance, I recommend you make it part of your antibiotic armamentarium as well. OM

1. Hovding G. Acute bacterial conjunctivitis. Acta Ophthalmol (Oxf) 2008 Feb;86(1):5-17.
2. Friedlaender MH. A review of the causes and treatment of bacterial and allergic conjunctivitis. Clin Ther. 1995 Sep-Oct;17(5):800-10; discussion 779.
3. Protzko E, Bowman L, Abelson M, et al. Phase 3 safety comparisons for 1.0% azithromycin in polymeric mucoadhesive eye drops versus 0.3% tobramycin eye drops for bacterial conjunctivitis. Invest Ophthalmol Vis Sci 2007 Aug;48(8):3425-3429.
4. Tabbara KF, al-Kharashi SA, al-Mansouri SM, et al. Ocular levels of azithromycin. Arch Ophthalmol 1998 Dec;116(12):1625-8.
5. Abelson MB, Shapiro AM, Heller W, and AzaSite Clinical Study Group. Efficacy of azithromycin 1% eye drops vs. vehicle as first-line therapy for bacterial conjunctivitis. Annual meeting of American Academy of Ophthalmology 2006; Abstract 74.
6. Masaharu S, Rubin BK. Macrolides and airway inflammation in children. Paediatr Respir Rev. 2005 Sep;6(3):227-35.
7. Amsden GW. Anti-inflammatory effects of macrolides — an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother. 2005 Jan;55(1):10-21.
8. Ianaro A, Ialenti A, Maffia P, et al. Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther. 2000 Jan;292(1):156-63.
9. Gladue RP, Bright GM, Isaacson RE, Newborg MF. In vitro and in vivo uptake of azithromycin (CP-62,993) by phagocytic cells: possible mechanism of delivery and release at sites of infection. Antimicrob Agents Chemother. 1989 Mar;33(3):277-82.

Dr. Karpecki, chair of the Refractive Surgery Advisory Committee to the American Optometric Association, is head of Research for the Cornea and Ocular Surface Disease Division at the Cincinnati Eye Institute. He serves on the editorial board of several professional journals. E-mail him at paul@karpecki.com.