Intravitreal voriconazole - An electroretinographic and histopathologic study
Intravitreal voriconazole - An electroretinographic and histopathologic study
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DOI：
10.1001/archopht.122.11.1687
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发表时间：
2004-11-01
影响因子：
--
通讯作者：
Holz, ER
中科院分区：
文献类型：
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作者：
Gao, H;Pennesi, ME;Holz, ER
背景：伏立康唑是一种新型的三唑类抗真菌剂，对酵母菌和霉菌具有广泛的抑制作用。目的：探讨伏立康唑作为玻璃体内药物治疗真菌性眼内炎是否安全。方法：采用啮齿类动物模型检测伏立康唑的视网膜毒性。将Voriconazole溶液依次稀释后通过玻璃体注射到正常成年Sprague-Dawley大鼠眼内，最终玻璃体浓度分别为5、10、25、50、500杯子/mL（每个浓度组n=3）。将生理盐水注射到所有动物的眼睛中作为对照。注射后三周，测量视网膜电图，随后摘除眼球进行组织学检查。结果：在视网膜电图研究中，测量了最大暗位b波、半饱和所需的强度和饱和a波振幅。在任何浓度组中，对照眼与伏立康唑注射眼记录的这些参数均无统计学差异。玻璃体内注射伏立康唑5 ~ 25马克杯/毫升，光镜组织学检查未见视网膜异常。伏立康唑剂量为50和500马克杯/mL时，偶见外视网膜小灶性视网膜坏死，尤其是在伏立康唑剂量为500马克杯/mL时。结论：大鼠视网膜玻璃体内注射高达25 mg/mL的伏立康唑不会引起视网膜电图改变或组织学异常。这表明伏立康唑是一种安全的抗真菌药物，可用于啮齿类动物玻璃体内注射，并可用于治疗人类真菌性眼内炎。
Background: Voriconazole, a novel triazole antifungal agent, presents potent activity against a broad spectrum of yeast and molds.Objective: To determine whether voriconazole could be safely used as an intravitreal agent in the treatment of fungal endophthalmitis.Methods: Retinal toxicity of voriconazole was examined in a rodent animal model. Voriconazole solutions were serially diluted and injected intravitreally into the eyes of normal adult Sprague-Dawley rats so that the final intravitreal concentrations were 5 mug/mL, 10 mug/mL, 25 mug/mL, 50 mug/mL, and 500 mug/mL (n=3 for each concentration group). Saline was injected into the fellow eyes of all animals as controls. Three weeks after injections, etectroretinograms were measured, and eyes were subsequently enucleated for histologic examination.Results: In electroretinographic studies, maximum scotopic b-wave, intensity needed for half saturation, 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 mug/mL of intravitreal voriconazole. In the eyes with 50 mug/mL and 500 mug/mL of voriconazole, small foci of retinal necrosis were occasionally observed in the outer retina, especially in the eyes with 500 mug/mL of voriconazole.Conclusions: Our results demonstrate that intravitreal voriconazole of up to 25 mg/mL causes no electroretinographic change or histologic abnormality in rat retinas. This indicates that voriconazole is a safe antifungal agent for intravitreal injection in rodents and may be used in the treatment of human fungal endophthalmitis following further study.