INTRAVITREAL HUMAN IMMUNE GLOBULIN IN A RABBIT MODEL OF STAPHYLOCOCCUS AUREUS TOXIN-MEDIATED ENDOPHTHALMITIS: A POTENTIAL ADJUNCT IN THE TREATMENT OF ENDOPHTHALMITIS

Abstract

Objectives: To test the feasibility of human immune globulin (IG, Gamimune N, 10%) as a new treatment for endoph-thalmitis, the ocular tolerance, distribution, and ability of intravitreal IG to attenuate the toxic effects of Staphyloccocus aureus culture supernatant were evaluated in a rabbit model. Methods: Effects of intravitreally injected IG were assessed histologically and with Western blot analysis performed 1 to 5 days after injection. IG reactivity to products of S aureus strain RN4220 was tested by Western blotting, using known toxins (beta hemolysin and toxic shock syndrome toxin-1) and a concentrated culture supernatant containing S aureus exotoxins (pooled toxin, PT). Endophthalmitis was induced by intravitreal PT injection. For treatment, IG and PT were mixed and injected simultaneously, or IG was injected immediately after, or 6 hours after, PT injection. PT toxicity was graded clinically and histologically over 9 days. Results: IG persisted intravitreally at least 5 days, inducing no clinical inflammation and minimal mononuclear cell infil-tration. In the endophthalmitis model, toxicity from PT was significantly reduced when IG was mixed with PT and injected simultaneously, or when IG was delivered immediately after PT. Only minimal clinically detectable reductions were observed when IG delivery was delayed 6 hours. Conclusions: Intravitreal IG is well tolerated in the rabbit eye and attenuates the toxicity of culture supernatant contain-ing S aureus exotoxins. Because toxin elaboration likely occurs gradually in true infection, reduced effects observed with delayed treatment in this toxin-injected model do not preclude clinical application. IG may represent a novel adjunct in endophthalmitis treatment. Trans Am Ophthalmol Soc 2004;102:305-32