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Andrew Perin, Valeriy V Lyzogubov, Nalini S Bora, Grant Morshedi; In Vitro Assessment of Moxifloxacin Toxicity to Human Iris Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5729.
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© ARVO (1962-2015); The Authors (2016-present)
Fluoroquinolone antibiotics, moxifloxacin (MFLX) in particular, have been suggested as causative agents of two recently described uveitic entities: bilateral acute iris transillumination (BAIT) and bilateral acute depigmentation of the iris (BADI). Furthermore, the popularity of intracameral MFLX use during surgery is growing. While dose-dependent toxicity of MFLX has been evaluated experimentally for several ocular cell lines, no study has investigated toxicity to human iris pigment epithelium (hIPE), which is implicated in BAIT and BADI. We hypothesize that MFLX does not exhibit direct toxicity to hIPE at therapeutic concentrations.
hIPE cells were cultured to 90% confluence and exposed to non-preserved MFLX hydrochloride at various concentrations (0, 1, 2, 5, 10, 50, 100, 150, 250, and 500µg/mL). 8 samples per concentration were analyzed. The cell cultures were incubated with MFLX for 48 hours at 37°C. Cell viability was then assessed utilizing an MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazonium bromide). An ELISA plate reader was used to measure the absorbance of each culture at a wavelength of 550nm. The absorbance data was converted to a cell viability percentage in relationship to the control. The peak and trough values were excluded for each concentration in the analysis. One-way ANOVA with post-hoc Dunnett t-test was used for statistical analysis with a significance level of p<0.05.
A significant toxicity effect emerged at concentrations of 100µg/mL and greater. At 100µg/mL, cell viability decreased to 84.12% (95% CI 77.21% to 91.02%) relative to the control group (95% CI 92.94% to 107.05%). This toxicity effect increased with greater MFLX concentrations, and at 500µg/mL cell viability decreased to 59.09% (95% CI 51.67% to 66.50%). No significant toxicity effect was observed for concentrations less than 100µg/mL.
The results confirm that MFLX does not exhibit direct toxicity to hIPE in vitro at therapeutic intraocular concentrations, which have been documented at ranges of 2-5µg/mL for systemic administration. While higher intraocular MFLX concentrations (up to 150µg/mL) can be achieved with intracameral administration, no reports of BAIT, BADI, or MFLX-associated uveitis exist following intracameral administration.
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