Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction:  a comparative clinical and spectroscopic pilot study.
OBJECTIVE
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 and principal component analysis. Terpenoids, short-chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (H-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 toward normal. Compared with 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 Fourier transform infrared spectroscopy-principal component analysis scores and relative area of the H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels 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 from 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 eyes. 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 eyes.
Department of Surgery, Robley Rex Veterans Affairs Medical Center, Louisville, KY, USA.
Gary N
GN
Foulks
Douglas
D
Borchman
Marta
M
Yappert
Shelley
S
Kakar
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D004318:Doxycycline / Q000627:therapeutic use*; D005141:Eyelid Diseases / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008537:Meibomian Glands / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010865:Pilot Projects; D025341:Principal Component Analysis; D011446:Prospective Studies; D017550:Spectroscopy, Fourier Transform Infrared; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D017963:Azithromycin; D004318:Doxycycline