Safety of intravitreal voriconazole: Electroretinographic and histopathologic studies

Hua Gao, Mark Pennesi, Kekul Shah, Xiaoxi Qiao, Seenu M. Hariprasad, William F. Mieler, Samuel M. Wu, Eric R. Holz, George W. Blankenship, William F. Mieler

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose: Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds. To determine whether it could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis, retinal toxicity of voriconazole was examined in a rodent animal model. Methods: Voriconazole solutions were serially diluted and injected intravitreally into eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 μg, 10 μg, 25 μg, 50 μg, and 500 μg/mL (N = 3 for each concentration group), Saline was injected into the fellow eyes of each animal as controls. Three weeks after injections, electroretinograms (ERGs) were measured, and eyes were subsequently enucleated for histologic examination, exai-nination, Results: In ERG studies, maximum scotopic b-wave, bmax, intensity needed for half saturation, I0.5, and saturated a-wave amplitude were measured. There was no statistically significant difference in these parameters recorded between control eyes and voriconazole-injected eyes in any concentration groups, Histologic examination with light microscopy did not reveal any retinal abnormality in the eyes with 5 to 25 μg/mL intravitreal voriconazole. In the eyes with 50 μg/mL and 500 μg/mL voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 mg/mL voriconazole. Conclusion: Our results demonstrate that intravitreal voriconazole of up to 25 mg/mL causes no ERG change or histologic abnormality in rat retina. This indicates that voriconazole is a safe antifungal agent that may be employed by intravitreal injection in the treatment of fungal endophthalmitis.

Original languageEnglish (US)
Pages (from-to)183-189
Number of pages7
JournalTransactions of the American Ophthalmological Society
Volume101
StatePublished - 2003
Externally publishedYes

Fingerprint

Safety
Endophthalmitis
Antifungal Agents
Retina
Eye Abnormalities
Voriconazole
Intravitreal Injections
Triazoles
Sprague Dawley Rats
Microscopy
Rodentia
Fungi
Necrosis
Animal Models
Yeasts
Light
Injections
Therapeutics

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Gao, H., Pennesi, M., Shah, K., Qiao, X., Hariprasad, S. M., Mieler, W. F., ... Mieler, W. F. (2003). Safety of intravitreal voriconazole: Electroretinographic and histopathologic studies. Transactions of the American Ophthalmological Society, 101, 183-189.

Safety of intravitreal voriconazole : Electroretinographic and histopathologic studies. / Gao, Hua; Pennesi, Mark; Shah, Kekul; Qiao, Xiaoxi; Hariprasad, Seenu M.; Mieler, William F.; Wu, Samuel M.; Holz, Eric R.; Blankenship, George W.; Mieler, William F.

In: Transactions of the American Ophthalmological Society, Vol. 101, 2003, p. 183-189.

Research output: Contribution to journalArticle

Gao, H, Pennesi, M, Shah, K, Qiao, X, Hariprasad, SM, Mieler, WF, Wu, SM, Holz, ER, Blankenship, GW & Mieler, WF 2003, 'Safety of intravitreal voriconazole: Electroretinographic and histopathologic studies', Transactions of the American Ophthalmological Society, vol. 101, pp. 183-189.
Gao, Hua ; Pennesi, Mark ; Shah, Kekul ; Qiao, Xiaoxi ; Hariprasad, Seenu M. ; Mieler, William F. ; Wu, Samuel M. ; Holz, Eric R. ; Blankenship, George W. ; Mieler, William F. / Safety of intravitreal voriconazole : Electroretinographic and histopathologic studies. In: Transactions of the American Ophthalmological Society. 2003 ; Vol. 101. pp. 183-189.
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AU - Mieler, William F.

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N2 - Purpose: Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds. To determine whether it could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis, retinal toxicity of voriconazole was examined in a rodent animal model. Methods: Voriconazole solutions were serially diluted and injected intravitreally into eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 μg, 10 μg, 25 μg, 50 μg, and 500 μg/mL (N = 3 for each concentration group), Saline was injected into the fellow eyes of each animal as controls. Three weeks after injections, electroretinograms (ERGs) were measured, and eyes were subsequently enucleated for histologic examination, exai-nination, Results: In ERG studies, maximum scotopic b-wave, bmax, intensity needed for half saturation, I0.5, and saturated a-wave amplitude were measured. There was no statistically significant difference in these parameters recorded between control eyes and voriconazole-injected eyes in any concentration groups, Histologic examination with light microscopy did not reveal any retinal abnormality in the eyes with 5 to 25 μg/mL intravitreal voriconazole. In the eyes with 50 μg/mL and 500 μg/mL voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 mg/mL voriconazole. Conclusion: Our results demonstrate that intravitreal voriconazole of up to 25 mg/mL causes no ERG change or histologic abnormality in rat retina. This indicates that voriconazole is a safe antifungal agent that may be employed by intravitreal injection in the treatment of fungal endophthalmitis.

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