Methotrexate Reduces the Complications of Endophthalmitis Resulting from Intravitreal Injection Compared with Dexamethasone in a Rabbit Model

PURPOSE: The incidence of infectious endophthalmitis associated with intravitreal injection (IVI) of steroid has been reported to be as high as 0.87%. This study was designed to investigate whether the antimicrobial activity of intravitreal methotrexate (MTX) alters the incidence or course of bacterial endophthalmitis associated with IVI in a rabbit model. METHODS: A rabbit model of endophthalmitis induced by Staphylococcus epidermidis (S) was established. Six groups of rabbits had IVI of sterile balanced salt solution (BSS), MTX (400 microg), dexamethasone (Dex, 200 microg), S, S and MTX (S-MTX), or S and dexamethasone (S-Dex). On days 0, 1, 3, 6, 10, and 14, total intraocular inflammation was measured in each animal. Vitritis was graded by the degree of vitreal haze. An intravitreal tap was performed on two animals from groups S, S-Dex, and S-MTX. A histopathologic study was performed on day 14. RESULTS: No endophthalmitis was observed in the control groups BSS, MTX, and Dex. Group S-Dex had the highest and group S-MTX had the least total ocular inflammation and vitritis scores from days 3 to 14. The difference in total inflammation and vitritis among groups S, S-Dex, and S-MTX is significant (P = 0.046 and P = 0.001, respectively). Live bacteria were isolated only from groups S and S-Dex. Pathology revealed severe ocular destruction in groups S and S-Dex and intact structures in group S-MTX. CONCLUSIONS: MTX appears to reduce the risk of development of bacterial endophthalmitis and ocular destruction associated with IVI compared with Dex. IVI of MTX may be a safer alternative than steroid injection in treating noninfectious uveitis.