Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

Abstract

BackgroundAny inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats.MethodsCorneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45+, CD4+, CD8+, CD25+, CD161+ and CD163+ cells were quantified via immunohistochemistry.ResultsAZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls.ConclusionsAlong with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Comparison of the Anti-angiogenic and Anti-inflammatory Effects of Two Antibiotics: Clarithromycin Versus Moxifloxacin

“…Antibiotics are used to prevent ocular infection after ocular trauma or surgery, 3,13-15 while steroids are used to prevent ocular inflammation and NV and to prevent immunological reactions such as graft rejection after corneal keratoplasty. [16][17][18][19] Among antibiotics, fluoroquinolone has been used worldwide perioperatively for several decades. 14,15 Recently, fourth generation fluoroquinolones have been developed and employed for their broad antibacterial activity.…”

“…However, azithromycin did not show any anti-angiogenic activity compared with control groups, even though it has activity sufficient to increase graft survival after corneal keratoplasty in rat and mouse models. 8,19 The purpose of using topical eyedrops after various ocular surgeries is to decrease infection, inflammation and angiogenesis. 18 Anti-angiogenesis and anti-LY may be important effects of topical agents such as topical steroid agents which are used perioperatively after ocular surgery.…”

Survey of Rejection Prophylaxis Following Suture Removal in Penetrating Keratoplasty in Germany

“…Lokal kann jedoch keines der bisher publizierten Medikamente die Effizienz von topischem Kortison erreichen [6]. Kortison allein [37,38]. Es wird bereits klinisch bei verschiedenen entzündlichen Oberflächenerkrankungen des Auges erprobt [39].…”

Effects of pre-transplant azithromycin administration on kidney graft function: study protocol for a double-blind randomized clinical trial

“…The effects of azithromycin in other organ transplantations have been previously shown. Azithromycin therapy following keratoplasty yielded results similar to those achieved with topical dexamethasone, without the risk of adverse effects commonly associated with steroidal drugs and enhanced graft survival in rats [ 17 ]. A study found that azithromycin promoted the survival of high-risk corneal allografts, apparently without modulating the immune system [ 18 ].…”