Ameri Hossein, Chader Gerald J, Kim June-Gone, Sadda Srinivas R, Rao Narsing A, Humayun Mark S
Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA.
Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5708-15. doi: 10.1167/iovs.07-0731.
To evaluate the effects of intravitreous bevacizumab in a rabbit retinal neovascularization model.
Twenty-four rabbits were divided into five groups. Group A included four rabbits; all other groups included five rabbits each. Group A received intravitreous VEGF only, and group E received intravitreous bevacizumab only. In groups B, C, and D, bevacizumab was injected at the same time, at day 2 and at week 1 after VEGF injection, respectively. Follow-up evaluations continued for 3 weeks and included color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Enucleated eyes were processed for hematoxylin and eosin (H&E) staining.
Intravitreous VEGF was associated with disc hyperemia, vascular dilatation and tortuosity, and fluorescein leakage at the disc and in the anterior chamber (AC) at day 2 and with formation of retinal neovascular membranes (NVM) by week 1. At weeks 2 and 3, the NVM was replaced by a fibrotic membrane and mild to moderate capillary nonperfusion. In groups B and C, injection of bevacizumab was very effective in preventing or stopping fluorescein leakage but was not able to prevent or reverse vascular dilatation and tortuosity completely. In group D, bevacizumab injection resulted in severe capillary nonperfusion at week 2.
Intravitreous injection of VEGF in rabbits results in florid retinal neovascularization within the first week, followed by closure of normal capillaries by week 2. Early intravitreous injection of bevacizumab can prevent these effects, whereas late injection may be associated with more significant closure of normal capillaries. A sudden drop in effective VEGF concentration may be responsible for the closure of the normal capillaries.
评估玻璃体内注射贝伐单抗在兔视网膜新生血管模型中的效果。
24只兔分为五组。A组4只兔;其他各组每组5只兔。A组仅玻璃体内注射血管内皮生长因子(VEGF),E组仅玻璃体内注射贝伐单抗。B、C、D组分别在注射VEGF的同时、第2天和第1周注射贝伐单抗。随访评估持续3周,包括彩色眼底照相、荧光素血管造影(FA)和光学相干断层扫描(OCT)。摘除眼球进行苏木精-伊红(H&E)染色。
玻璃体内注射VEGF在第2天与视盘充血、血管扩张和迂曲以及视盘和前房(AC)荧光素渗漏有关,到第1周时与视网膜新生血管膜(NVM)形成有关。在第2周和第3周,NVM被纤维膜取代,伴有轻度至中度毛细血管无灌注。在B组和C组中,注射贝伐单抗在预防或阻止荧光素渗漏方面非常有效,但不能完全预防或逆转血管扩张和迂曲。在D组中,注射贝伐单抗在第2周导致严重的毛细血管无灌注。
兔玻璃体内注射VEGF在第一周内导致视网膜新生血管大量形成,随后在第2周正常毛细血管闭合。早期玻璃体内注射贝伐单抗可预防这些效应,而晚期注射可能与正常毛细血管更显著的闭合有关。有效VEGF浓度的突然下降可能是正常毛细血管闭合的原因。