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November 1992

Toxicity of Intravitreous Ceftazidime in Primate Retina

Author Affiliations

From The Wilmer Eye Institute, The Johns Hopkins Hospital, Baltimore, Md. The authors have no proprietary interest in the materials and/or methods mentioned in this study.

Arch Ophthalmol. 1992;110(11):1625-1629. doi:10.1001/archopht.1992.01080230125035

• Squirrel monkeys were anesthetized and given intravitreous injections of 0.1 mL of balanced salt solution containing 0 mg (two eyes), 1 mg (three eyes), 2.25 mg (three eyes), or 10 mg (three eyes) of ceftazidime, a third-generation cephalosporin that provides excellent coverage for gram-negative infections. Ophthalmoscopic examinations were performed 48 hours after the injections and results were completely normal in all eyes except for those that were injected with 10 mg of ceftazidime, all three of which showed the appearance of cystic change in the macula. The monkeys were killed and the eyes were removed and examined by light and electron microscopy. All eyes were normal by light microscopy except for those injected with 10 mg of ceftazidime, which showed disruption of photoreceptors (primarily outer segments) in the foveas with cystic changes in all three and macular holes in two of three. Electron microscopy showed mild swelling of mitochondria and perinuclear halos around photoreceptor nuclei in both control eyes and in eyes injected with 1 and 2.25 mg. An eye injected with 10 mg showed severe damage to central photoreceptor outer segments consisting of disruption of plasma membranes and accumulation of intracytoplasmic granular material. Inner segments showed mild changes and there was loss of apical microvilli of the retinal pigmented epithelium. The inner retina was normal. These data suggest that high doses of intravitreous ceftazidime show toxicity primarily to photoreceptor cells, but a dose of 2.25 mg is safe as studied in this model and can be used instead of intravitreous aminoglycosides that have a narrow therapeutic window.

Vastine DW, Peyman GA, Guth SB.  Visual prognosis in bacterial endophthalmitis treated with intravitreal antibiotics . Ophthalmic Surg . 1979;10:76-83.
Puliafito CA, Baker AS, Haaf J, Foster CS.  Infectious endophthalmitis . Ophthalmology . 1982;89:921-929.Article
Davey PG, Barza M, Stuart M.  Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to 'late' treatment of infections . J Infect Dis . 1987;155:518-523.Article
Campochiaro PA, Conway BP.  Aminoglycoside toxicity—a survey of retinal specialists: implications for ocular use . Arch Ophthalmol . 1991;109:946-950.Article
Pflugfelder SC, Hernandez E, Fleisler SJ, Alvarez J, Pflugfelder ME, Forester RK.  Intravitreal vancomycin: retinal toxicity, clearance, and interaction with gentamicin . Arch Ophthalmol . 1987;105:831-837.Article
Snider JD III, Cohen HB, Chenoweth RG.  Acute ischemic retinopathy secondary to intraocular gentamicin . In: Ryan SJ, Division AK, Little HL, eds. Retinal Diseases . New York, NY: Grune & Stratton; 1985:227-232.
McDonald AR, Schatz H, Allen AW, et al.  Retinal toxicity secondary to intraocular gentamicin injection . Ophthalmology . 1986;93:871-877.Article
Conway BP, Campochiaro PA.  Macular infarction after endophthalmitis treated with vitrectomy and intravitreal gentamicin . Arch Ophthalmol . 1986;104:367-371.Article
Conway BP, Tabatabay CA, Campochiaro PA, D'Amico DJ, Hanninen LA, Kenyon KR.  Gentamicin toxicity in primate retina . Arch Ophthalmol . 1989;107:107-112.Article
Judson PH.  Aminoglycoside macular toxicity after subconjunctival injection . Arch Ophthalmol . 1989;107:1282-1283.Article
Verbist L, Verhaegen J.  GR-20263, a new aminothiazolyl cephalosporin with high activity against Pseudomonas and enterobacteriaceae . Antimicrob Agents Chemother . 1980;17:807-812.Article
Donowitz GR.  Third generation cephalosporins . Infect Dis Clin North Am . 1989;3:595-612.
Shockley RK, Fishman MD, Aziz M, Yannis RA, Jay WM.  Subconjunctival administration of ceftazidime in pigmented rabbit eyes . Arch Ophthalmol . 1986;104:266-268.Article
Jay WM, Fishman P, Aziz M, Shockley RK.  Intravitreal ceftazidime in a rabbit model: dose and time-dependent toxicity and pharmacokinetic analysis . J Ocul Pharmacol . 1987;3:257-262.Article
Fisher JP, Civiletto SE, Forster RK.  Toxicity, efficacy, and clearance of intravitreally injected cefazolin . Arch Ophthalmol . 1982;100:650-675.Article