In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis

Purpose. Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis. Methods. Eight patients (6 male, 2 female; mean age 45.7±17.5 years) were included in the study. Doxycycline (100 mg) was administered orally, twice a day, for 2 weeks and once a day for an additional 2 weeks. Clinical signs and symptoms were evaluated and scored (0-3) at baseline and after 4 weeks. Total sign (TSS) and total symptom (TSyS) scores were calculated. Tear samples and conjunctival impression cytologies were collected at baseline and after 4 weeks of treatment to evaluate MMP-9 and TIMP-1 expression and activity. Results. An improvement in TSS (4.5±1.1 vs 2.7±1.5) and TSyS (6.6±1.3 vs. 3.1±1.9) was observed after 4 weeks, with significant amelioration of hyperemia, marginal blepharitis, and superficial punctuate keratopathy. Zymography revealed a decrease of MMP-9 activity after 4 weeks. MMP-9 mRNA and protein levels did not change, while an upregulation of TIMP-1 expression was observed. Conclusions. This study suggests that 4-week treatment with doxycycline significantly improved symptoms and signs in patients with chronic blepharitis in association with a decrease in MMP-9 activity. Upregulation of TIMP-1 is proposed as a possible mechanism of MMP-9 inactivation.