Shahar Jonathan, Avery Robert L, Heilweil Gad, Barak Adiel, Zemel Esther, Lewis Geoffrey P, Johnson Patrick T, Fisher Steven K, Perlman Ido, Loewenstein Anat
Department of Ophthalmology, Tel-Aviv Medical Center, Israel.
Retina. 2006 Mar;26(3):262-9. doi: 10.1097/00006982-200603000-00002.
Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab.
Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration.
The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks.
Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.
玻璃体内注射贝伐单抗(阿瓦斯汀;基因泰克公司,加利福尼亚州旧金山)是年龄相关性黄斑变性的一种新治疗方法。本研究的目的是评估贝伐单抗的视网膜穿透性和毒性。
10只白化兔一只眼玻璃体内注射0.1 mL(2.5 mg)阿瓦斯汀,另一只眼注射0.1 mL生理盐水。分别于3小时、3天以及1、2和4周后记录视网膜电图(ERG)。4周后记录视觉诱发电位(VEP)。采用共聚焦免疫组织化学法评估视网膜穿透情况。
在整个随访期内,对照眼和实验眼的ERG反应在振幅和波形上相似。实验眼的闪光VEP反应波形和振幅正常,与仅刺激对照眼所记录的结果无差异。24小时时可见全层视网膜穿透,4周时基本消失。
基于电生理学研究,发现贝伐单抗对兔视网膜无毒。全层视网膜穿透可能解释了玻璃体内注射贝伐单抗所观察到的临床效果。尽管难以直接类推至人类,但我们的研究支持玻璃体内注射贝伐单抗的安全使用。