Potential benefits of oral antibiotics for MGD put into perspective

By Cheryl Guttman Krader

Studies investigating oral antibiotics for management of meibomian gland dysfunction (MGD) have shown their use provides some benefit. Research on this topic is limited, however, and oral antibiotic treatment is not free of risk, reported Edward J. Wladis, MD.

“I tend to reach for oral antibiotics to manage MGD that is refractory to other treatments, but it is incredibly important to have a very frank discussion with patients about the benefits that can be expected and the risks,” said Dr. Wladis, associate professor, Department of Ophthalmology, Albany Medical Center, Albany, NY. “I am hoping in the future to see well-designed studies that will provide a clearer roadmap of the indications for using antibiotics in this frustrating clinical setting.”

The oral antibiotics used often to treat MGD include tetracyclines-doxycycline, tetracycline, and minocycline-along with azithromycin. Dr. Wladis said there is good biologic plausibility to suggest that these agents should be effective considering their multimodal mechanisms of action.

First, they all are antimicrobials, and it is known that patients with MGD associated with rosacea have increased skin colonization with Demodex. In addition, all of those medications inhibit nitric oxide, which is a potent vasodilator that contributes to telangiectatic blood vessel formation. They also have anti-inflammatory properties mediated by suppression of B cell activation and inhibition of interleukin-1.

Evidence base

Serving on the American Academy of Ophthalmology Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel, Dr. Wladis and colleagues undertook a review of the role of oral antibiotics in the management of meibomian gland-related ocular surface disease [Wladis EJ, et al. Ophthalmology. 2016;123:492-496]. The lack of scientific evidence was surprising to Dr. Wladis.

“Considering the prevalence of the disease and the common use of oral antibiotics, I was sure this was a Herculean task that would require review of extensive literature,” he said. “Our search, however, only identified eight articles that suffered serious methodological flaws.”

Of the eight papers, four reported on doxycycline, and only one included a control group. One uncontrolled study of 8 patients with blepharitis treated for 4 weeks found significant improvement in signs and symptoms, but not in visual acuity or keratitis. A second uncontrolled study, including 39 patients with ocular rosacea treated for 12 weeks, found improved tear breakup time (TBUT), Schirmer scores, and eyelid inflammatory signs, but no improvement in keratitis or corneal staining.

In an uncontrolled study of 15 patients with ocular rosacea treated for 8 months, there was no improvement in keratitis or visual acuity, but 87% of patients reported resolution or significant improvements in symptoms.

Some doxycycline benefit

A single, controlled trial investigating doxycycline randomized 150 patients to doxycycline 20 or 200 mg twice daily or placebo. Its results showed the doxycycline groups had significantly improved TBUT and Schirmer test scores compared with the controls. Doxycycline treatment was not associated with improvement in visual acuity or corneal staining.

“The findings of these studies suggest there is some benefit to doxycycline, but it is certainly not the home run we would expect for a medicine we reach for,” Dr. Wladis said.

The literature review identified two articles reporting on minocycline. One was a randomized trial assigning 60 patients to treatment with artificial tears with or without minocycline and found the minocycline group benefited with improved TBUT, staining scores, and lid margin health.

“These results suggest some benefit for minocycline, but it was compared to an inferior modality,” Dr. Wladis said.

The second report was an observational study of 16 patients treated for meibomitis. After 3 months, there was improvement in eyelid appearance and health, but not in corneal staining or the Schirmer scores.

Azithromycin evaluated

The remaining two reports evaluated oral azithromycin prescribed at a dose of 500 mg/day for 3 consecutive days repeated for 3 or 4 weekly cycles. One prospective series including 13 patients with posterior blepharitis not responding to topical antibiotics and corticosteroids found improvement in TBUT and eyelid health but not in corneal staining.

The second group treated patients with papulopustular rosacea and found no improvement in the Schirmer score, TBUT, or corneal staining, but 87% of the treated patients experienced symptomatic improvement

The potential risks associated with the antibiotics used for management of MGD include photosensitivity, gastrointestinal disturbances (emesis, diarrhea, and dyspepsia), hypersensitivity, interference with anticoagulant medications, and genitourinary symptoms, and their use can also promote microbial resistance.

“It is important to juxtapose these risks against what may be a modest benefit for patients,” Dr. Wladis said.

Edward J. Wladis, MD

e. tedwladis@gmail.com

This article is based on a presentation given by Dr. Wladis at the 2016 American Academy of Ophthalmology meeting. He has no proprietary or commercial interest in any materials discussed in this article.