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Paul P. Connell, Emily Hart, Yu Qin Li, Russell Tait, Penelope J. Allen, Roy Robbins-Browne; Clinical Outcomes and Inoculum Dose Response in a Rabbit Model of Bacterial Endophthalmitis: How Much is Too Much?. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5590.
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Endophthalmitis is a sight-threatening inflammatory condition of the intraocular cavities. Staphylococcus aureus is the leading cause of postoperative and posttraumatic endophthalmitis and is often associated with both rapid onset of symptoms, and a poor visual outcome. While the full pathogenic mechanisms responsible for poor visual prognosis in S. aureus endophthalmitis are not well understood, direct toxic effects of secreted bacterial factors, and indirect tissue damage resulting from the host inflammatory response are generally considered to be causative. A delayed diagnosis allowing further replication to proceed is also postulated to exacerbate the clinical presentation, but little is known about this relationship. A dose response model of bacterial endophthalmitis is described.
: A model of bacterial endophthalmitis was created in New Zealand White rabbits by injection of various doses of S. aureus ATCC strain 29213 into the posterior segment of the eye. Outcome measures included a modified clinical grading scheme, anterior segment and fundal photography.
Indirect ophthalmoscopy showed clinical presentation of endophthalmitis indistinguishable from that seen in humans (Peyman grades 0 to 4 across parameters), with severe disease developing within three to seven days after inoculation. Altering the dose of the infecting inoculum controlled the speed of onset and severity of symptoms, showing a predictable and graded response by the host immune system and histologically. While low doses (10 organisms) caused mild introacular inflammation, higher inoculum doses (>100 organisms) induced such an overwhelming host response that the health of the eye was unsalvageable. Conventional gold-standard treatment by intravitreal injection of Vancomycin (1.0 mg/ml) and Ceftazidime (2.25 mg/ml) ameliorated clinical signs and restored the experimental eye to a healthy state.
Confirming treatment validity in this model has now provided a platform for testing the efficacy of novel antimicrobial and anti-inflammatory treatment strategies in targeting bacterial endophthalmitis.
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