Topical Azithromycin and Oral Doxycycline Therapy of Meibomian Gland Dysfunction

Abstract

Purpose Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment. Methods Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid-lipid interaction strength, conformation and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy (FTIR) and principal component analysis (PCA). Terpenoids, short chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (1H-NMR) spectrometer. Results Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion towards normal. Compared to 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the FTIR PCA scores and relative area of the 1H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the 1H-NMR resonances at 5.2 and 7.9 ppm to normal levels. The level of meibum protein and meibum lipid oxidation were not influenced by azithromycin or doxycycline treatment. Conclusions The mechanism of action of doxycycline may be different than that of azithromycin in therapy of MGD. It is notable that when carotenoids in meibum are low, as in MGD, the tear film is unstable and patients have the signs and symptoms of dry eye. When carotenoids are restored with azithromycin and doxycycline treatment, tear film stability is restored and patients no longer have the signs and symptoms of dry eye.

Additional Instruction by a Nurse Enhanced the Effect of Eyelid Warming on Subjective Symptoms in Patients with Meibomian Gland Dysfunction

“…Various treatment options for MGD including the LipiFlow instrument, intense pulsed light, eyelid-warming devices, intraductal probing, as well as topical or oral application of drugs have been developed [11][12][13][14][15][16][17][18][19]. Our present results regarding additional instruction by nurses for improving the outcome of treatment with the Azuki-no-chikara eyelid-warming device may also be applicable to other treatment approaches.…”

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

“…6 Antibiotics that also have immunomodulatory functions such as macrolides (azithromycin) and tetracyclines (doxycycline) have yielded several reports of successful improvement in the signs and symptoms of MGD with topical and oral azithromycin, [36][37][38] and oral doxycycline. 36,39,40 All the refractory patients in our cohort had clinically non-apparent inflammation on IVCM, quantification of which demonstrated increased densities of both palpebral conjunctival epithelial and stromal immune cells as compared with MGD patients with improved symptoms. Corneal DC density was also elevated, which went undetected by routine slit-lamp examination.…”

Limited Azithromycin Localization to Rabbit Meibomian Glands Revealed by LC-MS-Based Bioanalysis and DESI Imaging

“…19,20) Indeed, topical azithromycin therapy relieved the signs and symptoms of MGD and restored the biophysical properties of meibomian lipids to normal. 5,21) Furthermore, azithromycin topical treatment significantly reduced the number of plugged orifices and ameliorated acinar atrophy in a special diet-induced MGD mouse model. 10) These reports support the hypothesis that azithromycin might exert its pharmacological effect directly on the meibomian gland cells to subsequently restore normal lipid properties.…”

“…Indeed, several clinical studies have demonstrated that topical azithromycin ophthalmic solution significantly relieved the clinical signs and symptoms of MGD. [4][5][6] Although significant progress has been made in human clinical studies to better understand the mechanism of MGD, fundamental pharmaceutical research still lags behind. Most recently, several animal models have been established based on MGD pathogenesis or specific signs.…”