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M Livia Bajenaru, Andrea Rachelle Santos, Mitchell Falter, Marco Ruggeri, Jamie Ponmattam, Eleut Hernandez, Mohamed Abou Shousha, Victor Perez, Darlene Miller, Eduardo Alfonso; Preclinical evaluation of new therapies in a fungal keratitis rat model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5992.
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© ARVO (1962-2015); The Authors (2016-present)
One of the most important risk factors for infectious keratitis is extended contact lens (CL) wear. 6-20% of infectious keratitis cases are fungal, and Fusarium is the most causative organism. Delay in the diagnosis and relative resistance to antifungal treatment are responsible for significant morbidity in fungal keratitis. We recently characterized a new rat CL Fusarium keratitis model. The purpose of this study is to assess the diagnostic and follow-up capability of spectral domain optical coeherence tomography (SD-OCT) and a new combination antifungal therapy with Amphotericin B and rapamycin in CL related fungal keratitis.
Fusarium infection was initiated in Sprague-Dawley rats (n=24) by corneal epithelial abrasion and fitting CL soaked in Fusarium solani 105 CFU/ml for 4 hours. A saline soaked CL was used in control animals (n=6). Rats were treated daily with topical 0.15% Amphotericin B at days 1-7, 10, and 13 post-infection (n=6). 2mg/kg Rapamycin only (n=6), or in combination with Amphotericin B (n=6) was administered intraperitoneally in the same time regimen. The infection was monitored periodically by slit lamp (SL), and SD-OCT at 840 nm at 1, 3, 7, 9, 14 days post-infection. Central (CCT), and peripheral corneal thickness (PCT) were measured on selected radial B-scans.
SD-OCT imaging correlated well with SL and revealed thickening of the cornea, endothelial plaques, and inflammatory cells infiltrates. In infected animals the average CT was highly increased, CCT=245.5±69.9; PCT=229.6±62.27, when compared with control, CCT=155.72±11.2; PCT=151.5±10.46. Amphotericin treatment alone remarkably reduced CT to CCT=176.20±31.5; PCT=174.98±29.4, and rapamycin further potentiated the effect of amphotericin to CCT=171.76±46.66; PCT=162.02±36.7. CT reached a peak of CCT=343.1±71.9; PCT=322.41±38.85 at 3 days post-infection. This peak was decreased to CCT=265.20±8.02; PCT=228.9±12.5 by amphotericin, and to CCT=201.75±37.42; PCT=201.64±51.3 by combination amphotericin and rapamycin treatment. Combination therapy resulted also in faster recovery, CT reaching normal values at day 7, while amphotericin only treatment at day 9 post-infection.
We were able to quantitatively evaluate by SD-OCT the disease progression and treatment in the CL Fusarium keratitis model. Combination therapy with amphotericin B, and rapamycin efficiently reduced the severity of the infection and the time of recovery.
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