Importance of Prophylaxis for Lid Margin and Ocular Surface Disease in the Surgical Setting

ByJodi I. Luchs, MD, FACS

The clinical signs and symptomatology of blepharitis result in physical, cosmetic, and social discomfort and can interfere with daily activities. In addition, these diseases can have a serious impact on the success and outcome of ocular surgery, as exemplified in Foulks’ classification of blepharitis (Figure 1).¹ For example, anterior blepharitis is presumed to be an infectious condition due to the overgrowth of gram-positive staphylococcus and streptococcus bacteria on the lid margin. Studies performed in the early 1990s demonstrated that the primary source of causative organisms in postoperative infections was the patient’s lids, lashes, and conjunctiva.² In 1 study, these bacteria were responsible for 94% of postoperative endophthalmitis cases and, in another more recent study, they were responsible for 36% of infections following refractive surgery.^3,4 In addition, atypical mycobacteria, another organism that colonizes lid margins, was responsible for 48% of post-LASIK infections.⁴

Figure 1: Foulks Classification System of Blepharitis/Lid Margin Disease

Accordingly, if a condition characterized by an overgrowth of bacteria is encountered, such as anterior blepharitis, it is essential to treat it preoperatively to reduce the risk of postoperative surgical infection. This practice should be applied in cases of posterior blepharitis as well, which is characterized by reduction and changes in meibomian gland secretions that result in an abnormal, unstable lipid layer in the tear film. A normal lipid layer assists with lubrication and restricts evaporation to 5% to 10% of tear flow, which is disrupted in cases of posterior blepharitis. In addition to increased evaporative tear loss, an unstable tear film leads to fluctuations in visual acuity, which can potentially delay visual recovery following ocular surgery. In fact, several studies have shown that optimization of the tear film preoperatively is associated with the best visual result following refractive surgery. In addition, the unstable tear film can potentially affect or delay corneal healing after clear corneal cataract surgery or corneal refractive surgery and can also worsen post-LASIK dry eye. A stable tear film is necessary to achieve an optimal keratometry reading before cataract surgery and to allow optimal corneal topography and reliable wavefront readings prior to refractive surgery. With increasing patient expectations as well as current technological advances including clear corneal cataract surgery, topical anesthesia, presbyopic IOLs, and toric IOLs, it is essential to optimize the tear film preoperatively. Therefore, preexisting blepharitis and lid margin disease must be appropriately treated to reduce the risk of infection, maximize tear-film stability, and optimize recovery of vision postoperatively.

Classic treatments for anterior blepharitis include warm compresses and lid scrubs to reduce crusting and staphylococcal bacteria on the lid margin (Figure 2), and application of antibiotic ointments including bacitracin and erythromycin. The effectiveness of an ointment is hampered by limited compliance due to difficulty with the application, gumming of the ointment on the eyelids, and interference with vision. Classic treatments for posterior blepharitis include warm compresses and lid massage; however, patients are poorly compliant with this therapy and it may require several weeks or months of treatment to improve the quality of the meibomian gland secretions. Oral tetracycline antibiotics including tetracycline, minocycline, and doxycycline, and oral macrolides including erythromycin are also used. These agents can relieve inflammation and open the obstructed glands; however, they may also require long-term treatment to be effective and can be poorly tolerated due to systemic side effects.

These limitations indicate that an ideal treatment is not yet available. Accordingly, the classic treatments for both anterior and posterior disease tend to be inadequate for patients undergoing ocular surgery. Characteristics of an ideal therapy include sufficient antibiotic effectiveness and adequate penetration into the affected tissues. In addition, anti-lipase activity is important to inhibit breakdown of the abnormal meibomian gland secretions into the fatty acids and soaps that cause significant discomfort and inflammation on the ocular surface. Anti-inflammatory activity on the lid margin and ocular surface is important to relieve patient discomfort. Finally, dosing regimen and formulation should be convenient to promote patient compliance.

Azithromycin opththalmic solution, currently indicated for the treatment of bacterial conjunctivitis, possesses many of these attributes; accordingly, it is a potential candidate for the treatment of lid margin disease, especially prior to ocular surgery. It is an effective broad-spectrum antibiotic, active against most of the common bacteria that are responsible for producing lid margin disease. The oral and intravenous formulations are associated with high tissue penetration, and the topical ophthalmic formulation now available also produces sustained high levels of the drug on the ocular surface and in ocular surface tissues, as demonstrated in both animal and human studies. The azithromycin ophthalmic solution vehicle forms a muco-adhesive matrix with the azithromycin that binds to the mucin-coated surfaces of the eye, increasing its bioavailability by enhancing its retention on the ocular surface and allowing high drug concentrations to develop in ocular surface tissues. Azithromycin has anti-inflammatory properties as well, which have been demonstrated in several tissues. Anti-inflammatory activity in ocular tissues, especially against matrix metalloproteinases, is currently under investigation.

Phase 4 studies have evaluated the efficacy of azithromycin for treating lid margin disease and were discussed earlier in this monograph. To briefly review 3 major studies, azithromycin ophthalmic solution was shown to be more effective than erythromycin ointment for the treatment of anterior blepharitis after 4 weeks of therapy. A multicenter 4-week study demonstrated the efficacy of azithromycin ophthalmic solution as a monotherapy for mixed anterior and posterior blepharitis. Finally, azithromycin combined with standard warm compress therapy was superior to compress therapy alone for the treatment of posterior blepharitis after 2 weeks of therapy. In that study, 44% of patients demonstrated complete resolution of meibomian gland plugging after the 2-week treatment, and 22% had a complete normalization of the quality of the meibomian gland secretions.

In summary, blepharitis, when not treated successfully prior to ocular surgery, can be associated with suboptimal surgical outcomes including infection, poor healing, suboptimal recovery of visual acuity, and a potential increase in postoperative discomfort. Conventional therapies may not be adequate for preoperative patients. Azithromycin ophthalmic solution has been shown to be efficacious for the treatment of anterior and posterior lid margin disease and may be an effective and convenient option for patients with blepharitis who are undergoing ocular surgery.

References

Foulks GN. Blepharitis: Lid margin disease and the ocular surface. In: Holland EJ, Mannis MJ, eds. Ocular Surface Disease: Medical and Surgical Management. Springer. 2002:39-48.
Speaker MG, Milch FA, Shah MK, Eisner W, Kreiswirth BN. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology. 1991;98:639-649.
EVS Study Group. Results of the Endophthalmitis Vitrectomy Study: A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthlmitis. Archives of Ophthalmology. 1991;98:639-649.
Soloman R, Donnenfeld ED, Azar DT, Holland EJ, Palmon FR, Pflugfelder SC, Rubenstein JB. Infectious keratitis after laser in situ keratomileusis: results of an ASCRS survey. Journal of Cataract and Refractive Surgery. 2003;29:2001-2006.