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.
Highlights
Corneal transparency is essential for optimal vision
We studied the effects of topically applied AZM in a wellestablished rat keratoplasty model [12,18] with a particular emphasis on the adequate time frame for treatment
Azithromycin (AZM) is a well-known antibiotic agent approved for topical use against ocular surface infections [21,22,23,24,25,26]
Summary
Corneal transparency is essential for optimal vision. Inflammatory processes at the ocular surface can severely affect corneal transparency because of possible leukocytic infiltration, vascularization and scar formation and subsequent disruption of the ocular immune privilege [1]. With less than 10% of corneal grafts being rejected [4] This is mainly due to the immune-privileged status of the eye and the cornea [5] and holds true for low-risk situations, e.g., keratokonus or Fuchs' dystrophy [4]. Even in these patients, topical corticosteroids are essential as a mainstay treatment during the first months following keratoplasty [6] to reduce corneal inflammation and corneal lymph- and hemangiogenesis [7,8]. Our data supports the use of AZM to prevent corneal graft rejection and we strongly suggest that short-term perioperative application is sufficient to abrogate graft failure
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