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S. Deng, D.A. Goldstein, S. Pendland, R. Fiscella, S. Gupta, D. Edward, H.H. Tessler; Antimicrobial Effect of Methotrexate in an Experimental Model of Bacterial Endophthalmitis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2781.
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Purpose: Intraocular injection (IVI) of corticosteroid is becoming a frequently used treatment for many ocular conditions. However, the incidence of bacterial endophthalmitis associated with IVI of steroid has been reported to be as high as 0.87%. Intravitreal methotrexate (MTX) is used to treat intraocular lymphoma, and there is evidence from animal studies that it could be used to treat intraocular inflammation. This study was designed to investigate whether the antimicrobial activity of intravitreal MTX could reduce the risk or alter the course of bacterial endophthalmitis in a rabbit model. Methods: A rabbit model of endophthalmitis induced by Staphylococcus epidermidis (Staph) was established. Six groups of rabbits had IVI of sterile balanced salt solution (BSS), MTX, dexamethosone (Dex), Staph(S), Staph and MTX (S–MTX), or Staph and Dex (S–Dex), respectively. On days 0, 1, 3, 6, 10 and 14, intraocular inflammation was measured by the severity of conjunctival hyperemia, anterior chamber reaction, and vitreal haze. Intravitreal tap was performed on 2 eyes with significant vitritis in groups S, S–Dex and S–MTX to recover live bacteria. One or 2 eyes representative of each group were enucleated for pathologic study on day 14. Results:No endophthalmitis was observed in groups BSS, MTX and Dex. Ocular inflammation reached maximum on day 6 then declined in groups S, S–MTX, and S–Dex. There was significantly more vitritis in group S–Dex than in group S–MTX (P<0.05). A consistent trend of increasing ocular inflammation was noted from group S–MTX, S to S–Dex since day 1 (day 14, S–Dex vs S–MTX, P<0.05; S vs S–MTX , P=0.067). Group S–Dex had higher risk of developing endophthalmitis than group S–MTX (100% vs 56%, P= 0.08). Live bacteria were isolated from both eyes in groups S and S–Dex, but none from group S–MTX on day 6. Pathologic study revealed various degrees of vitreous abscess, retinal necrosis, and choroiditis in both groups S and S–Dex. Minimal localized retinal infiltrates and intact ocular structures were observed in group S–MTX. Conclusions: This study demonstrated that the in vivo antimicrobial activity of MTX appeared to reduce risk of developing bacterial endophthalmitis associated with IVI, shorten the course of the infection, and result in less ocular inflammation and destruction. Intravitreally injected MTX may be a safer treatment option than intravitreal steroid for intraocular inflammation.
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