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Junzo Kinoshita, Noriaki Iwata, Mitsuhiro Ohba, Tomofumi Kimotsuki, Mitsuya Yasuda; Mechanism of Voriconazole-Induced Transient Visual Disturbance: Reversible Dysfunction of Retinal ON-Bipolar Cells in Monkeys. Invest. Ophthalmol. Vis. Sci. 2011;52(8):5058-5063. doi: 10.1167/iovs.11-7183.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the mechanism of voriconazole-induced transient visual disturbance in humans.
Standard full-field electroretinograms (ERGs) were recorded from monkeys treated intravenously with voriconazole. In addition, photopic ERGs elicited by long-duration stimuli (ON-OFF response) were also recorded from monkeys receiving intravenous voriconazole or intravitreal 2-amino-4-phosphonobutyric acid (APB).
Characteristic changes were observed in the waveform of the standard full-field ERGs obtained immediately after dosing of voriconazole as follows: electronegative combined rod-cone response (markedly attenuated b-wave and oscillatory potentials), undetectable rod response (eliminated b-wave); slightly abnormal single-flash cone response (flattened appearance in the bottom of the a-wave, mildly attenuated b-wave); and slightly abnormal 30 Hz flicker (mildly attenuated b-wave). The above changes fully recovered to baseline 24 hours after each dosing, along with a decrease in plasma voriconazole concentration. In addition, the change in the waveform of the ON-OFF response recorded in voriconazole-treated monkeys was quite similar to that recorded in APB-treated monkeys as follows: the b-wave was eliminated or prominently attenuated; and the a- and d-waves were not apparently attenuated.
The results strongly suggest that voriconazole induces selective and reversible dysfunction of the retinal ON-bipolar cells in both the rod and cone pathways in monkeys. From the results obtained in monkeys in this study, it is suggested that the function of the retinal ON-bipolar cells was selectively and reversibly affected in voriconazole-treated humans who complained of transient visual disturbances.
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