Manzano Roberta P A, Peyman Gholam A, Khan Palwasha, Kivilcim Muhamet
Department of Ophthalmology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112-2699, USA.
Retina. 2006 Mar;26(3):257-61. doi: 10.1097/00006982-200603000-00001.
To evaluate the retinal toxicity of varying doses of bevacizumab when injected intravitreally in rabbits. Bevacizumab has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer.
Twelve New Zealand albino rabbits were used for this study and divided into four groups. Four concentrations of bevacizumab were prepared: 500 microg/0.1 mL, 1.0 mg/0.1 mL, 2.5 mg/0.1 mL, and 5.0 mg/0.2 mL. Each concentration was injected intravitreally in one eye of each of three rabbits; 0.1 mL volume of sterile balanced saline solution was injected into the contralateral eyes. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, or toxicity. A baseline electroretinogram (ERG) was performed before the drug treatment and at day 14 before the animals were killed. The enucleated eyes were prepared for histologic evaluation of retinal toxicity.
Histologic and ERG results in all groups showed no retinal toxicity. However, some inflammatory cells were found in the vitreous at the 5-mg dose.
Intravitreal bevacizumab did not appear toxic to the retina in albino rabbits at a concentration of 2.5 mg. Intravitreally injected bevacizumab should be evaluated for efficacy in choroidal neovascularization and macular edema.
评估不同剂量的贝伐单抗玻璃体内注射对兔视网膜的毒性。贝伐单抗已获美国食品药品监督管理局批准用于治疗转移性结直肠癌。
本研究使用12只新西兰白化兔,分为四组。制备了四种浓度的贝伐单抗:500微克/0.1毫升、1.0毫克/0.1毫升、2.5毫克/0.1毫升和5.0毫克/0.2毫升。每种浓度分别注射到三只兔子每只眼睛的玻璃体中;对侧眼睛注射0.1毫升无菌平衡盐溶液。进行裂隙灯和眼底检查,并观察动物2周,以寻找感染、炎症或毒性迹象。在药物治疗前及处死动物前第14天进行基线视网膜电图(ERG)检查。摘除眼球,准备进行视网膜毒性的组织学评估。
所有组的组织学和ERG结果均未显示视网膜毒性。然而,在5毫克剂量组的玻璃体中发现了一些炎性细胞。
在白化兔中,2.5毫克浓度的玻璃体内注射贝伐单抗对视网膜似乎无毒。玻璃体内注射贝伐单抗在脉络膜新生血管和黄斑水肿方面的疗效应进行评估。