The Effect of Low-Dose Doxycycline Therapy in Chronic Meibomian Gland Dysfunction

Abstract

Blepharitis is a relatively common disorder that manifests various clinical signs such as foreign body sensation, tearing and dry sensation, etc. The complete treatment of this condition is believed to be difficult because of abnormal meibomian gland function and changes in the normal flora of conjunctiva. Consequently, the course is often chronic, frustrating both clinicians and patients. Meibomian gland dysfunction is a common type of chronic blepharitis and although it is so common it can be easy to overlook clinically. Because symptoms can improve with appropriate treatment, it is very important to identify the disorder in patients who complain of dry eye symptoms.Chronic meibomian gland dysfunction particularly affects the lipid layer of tear film, destabilizing the tear film and quickening the tear film's evaporation, and ultimately causes many disorders of the external eye, including dry eye syndrome. 1In order to treat this dysfunction, physicians have reported prescribing 200 mg twice-daily doxycycline (α -6 deoxy-5 hydroxytetracycline), a long acting analogue of tetracycline that inhibits collagenase and also has antichemotactic effects, thus improving patients' symptoms by stabilizing the lipid layer of tear film. Recently, in the field of dentistry, low-dose doxycycline hyclate (20 mg) has been used to treat and prevent periodontitis by inhibiting collagenase. 3 The authors wanted to investigate the effectiveness of such therapy in the chronic meibomian gland dysfunction patients.One hundred fifty patients were selected (55 male, 95 female) that reported to the department of ophthalmology between January and December of 2003 and newly diagnosed with chronic meibomian gland dysfunction with grade 2 or worse meibomian gland destruction or meibomian gland Department of Ophthalmology, Dankook University College of Medicine, Cheonan, KoreaPurpose: The aim was to investigate the effect of low dose doxycycline (20 mg) therapy in patients with chronic meibomian gland dysfunction that were refractory to conventional therapy. Methods: The randomized prospective study enrolled 150 patients (300 eyes) who have chronic meibomian gland dysfunction and who didn't respond to lid hygiene and topical therapy for more than 2 months. All topical therapy was stopped for at least 2 weeks prior to beginning the study. After conducting the tear break up time test (TBUT) and Schirmer test, the authors randomly divided the patients into three groups a high dose group (doxycycline, 200 mg, twice a day), a low dose group (doxycycline, 20 mg, twice a day) and a control group (placebo). After one month, the author repeated the TBUT and Schirmer tests, and analyzed the degree of symptomatic improvement. Results: Compared to the control group, both the high and low dose group showed statistically significant differences after treatment in TBUT, Schirmer test, the number of symptoms reported and the degree of improvement of subjective symptoms. However, there was no statistically significant difference between the high and low dose ...

The evaluation of the treatment response in obstructive meibomian gland disease by in vivo laser confocal microscopy

“…Although MG drop-out and expressibility grades did not change at the end of 3 months in the anti-inflammatory treatment group, the tear stability and fluorescein staining scores improved significantly, along with improvement of lid injection and clearance of debris in slit-lamp microscopy. We attributed these favourable changes to the anti-inflammatory effects of minocycline, a tetracycline derivative, which has been reported to attenuate TNF-alpha production and downregulate proinflammatory cytokine output from lymphocytes, and decrease neutrophilic adhesion at sites of inflammation [22][23][24]. Topical steroid use, known to inhibit migration of a wide array of inflammatory cells, release of IL-1, TNFalpha and IL-6 from inflammatory cells and neutrophil adhesion might have very well acted together with minocycline to achieve these favorable effects on the tear film and the ocular surface [25].…”

“…Bacterial pathogens have been shown to release lipases which can break down meibomian lipids to diglycerides and free fatty acids, which are highly toxic to the ocular surface epithelium [23]. Minocycline has been shown to decrease the production of diglycerides and free fatty acids in MG secretions, through a direct effect on the ocular flora [22][23][24]. Tetracycline derivatives have also been shown to preserve the integrity of corneal epithelial tight junctions, barrier function, and decrease the corneal epithelial cell apoptosis and desquamation in murine dry eye models through a decrease in MMP-9 protein [28].…”

Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration

“…2 Additionally, doxycycline becomes concentrated in the meibomian and lacrimal glands, 3 and even low-dose oral administration of doxycycline has been reported to be effective at treating meibomian gland dysfunction in humans. 4 Furthermore, doxycycline is frequently administered to pinnipeds and has a broad spectrum of activity against Chlamydia spp, Mycoplasma spp, Rickettsia spp, aerobic and anaerobic Gram-positive and -negative bacteria, Brucella spp, Bartonella spp, and Leptospira spp, among others. 5,6 Pinnipeds are commonly infected with many of those important and often zoonotic pathogens, particularly those in the genera Leptospira, Brucella, and Bartonella, [7][8][9][10][11] making doxycycline a justifiable antimicrobial choice in many instances.…”

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.…”