Document Detail


Mechanism of Voriconazole-Induced Transient Visual Disturbance: Reversible Dysfunction of Retinal ON-Bipolar Cells in Monkeys.
MedLine Citation:
PMID:  21436272     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE. To investigate the mechanism of voriconazole-induced transient visual disturbance in humans. METHODS. 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). RESULTS. 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. CONCLUSIONS. Our 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.
Authors:
Junzo Kinoshita; Noriaki Iwata; Mitsuhiro Ohba; Tomofumi Kimotsuki; Mitsuya Yasuda
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-24
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  -     ISSN:  1552-5783     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd., 717, Horikoshi, Fukuroi, Shizuoka 437-0065, Japan.
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