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Natalie A. Afshari, Rachelle A. Rebong, Ricardo M. Santaella, Christopher P. Majka, Brian E. Goldhagen, William J. Steinbach; Study of Polyhexamethylene Biguanide and Calcineurin Inhibitors for the Treatment of Aspergillus Keratitis in a Murine Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2934.
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To establish a novel mouse model of Aspergillus keratitis and to assess the ability of the calcineurin-inhibitor cyclosporin A (CsA) to work synergistically with voriconazole (VCZ), amphotericin B (AMB), and polyhexamethylene biguanide (PHMB) against Aspergillus keratitis in vivo.
The corneas of BALB/c mice were scarred and then inoculated with wild type A. fumigatus to produce infection. An ophthalmologist masked to the treatment groups assessed disease severity daily based on a grading scale from 0 (no disease) to 4 (severe disease). Infected mice were randomly assigned to groups being treated with saline (control), AMB, VCZ, PHMB, CSA, VCZ+CSA, AMB+CSA, or PHMB+CSA. The mean change in disease score between groups was compared using an analysis of variance and the Student's t-test.
A novel murine model of Aspergillus keratitis was established with a 65% infection rate. The mean end change in disease score per group were as follows (mean end change ± SD): saline -1.08 ± 1.08, AMB -1.84 ± 1.28, AMB+CSA -1.11 ± 1.12, VCZ -1.53 ± 0.78, VCZ+CSA -0.42 ± 1.22, PHMB -0.96 ± 1.27, and PHMB+CSA -1.39 ± 1.16. Although all treatment groups showed significant disease improvement compared to the control group (p < 0.05), pairwise comparisons between treatment groups were not significant.
A novel murine model of Aspergillus keratitis was established. PHMB is effective in treating Aspergillus keratitis in vivo. The use of calcineurin inhibitors to treat Aspergillus keratitis warrants further investigation.
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