Keshet Yariv, Gal-Or Orly, Schaap Fogler Michal, Mimouni Karin, Ben Ishai Meydan, Weinberger Dov, Dotan Assaf
Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Int J Retina Vitreous. 2021 Sep 8;7(1):53. doi: 10.1186/s40942-021-00322-8.
As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists.
Choroidal neovascular lesions (CNV) were induced in the right eye of 12 brown Norway rats, using indirect laser ophthalmoscope. Intravitreal Aflibercept injection (0.12 mg/3 µl) was performed 3 days after CNV induction. Rats were euthanized at predetermine time intervals of 3, 6, 24 and 48 h post injection, with immediate enucleation for histological analysis with H&E and immunofluorescence staining. Aflibercept molecules were stained with red fluorescence thanks to the formation of the immune complex Aflibercept-Rabbit anti human IgG-Anti rabbit antibodies-Cy3.
Immediately after the injection, a strong fluorescence signal was detected, indicating the presence of Aflibercept in the iridocorneal angle. At 3- and 6-h interval a strong signal of Aflibercept was still seen. Six hours post injection, the signal was highly concentrated in Schlemm's canal. In the 2 eyes harvested 24 h post Aflibercept injection, red fluorescence signal intensity was decreased in one eye, occupying mainly intra scleral venous plexuses, and absent in the other eye. At 48 h there was no fluorescence signal, confirming complete clearance of Aflibercept.
In our rat model, a complete clearance of Aflibercept from the anterior chamber angle, was seen 48 h after the injection. This finding refutes the theory of possible connection between IOP elevation and mechanical obstruction. Evacuation time of Aflibercept through the angle is of the same magnitude as that of Bevacizumab in the same rat model.
随着玻璃体内抗血管内皮生长因子（VEGF）注射成为许多视网膜疾病的主要治疗方法，继发性持续性眼压升高的原因仍不清楚。我们研究的目的是在大鼠模型中研究阿柏西普从前房角的清除情况，以测试是否存在聚集现象。
使用间接检眼镜在12只棕色挪威大鼠的右眼诱导脉络膜新生血管病变（CNV）。在CNV诱导后3天进行玻璃体内阿柏西普注射（0.12mg/3μl）。在注射后预先确定的3、6、24和48小时时间间隔对大鼠实施安乐死，并立即摘除眼球进行苏木精和伊红（H&E）染色及免疫荧光染色的组织学分析。由于阿柏西普-兔抗人IgG-抗兔抗体-赛罗菁（Cy3）免疫复合物的形成，阿柏西普分子被染成红色荧光。
注射后立即检测到强烈的荧光信号，表明前房角存在阿柏西普。在3小时和6小时间隔时仍可见强烈的阿柏西普信号。注射后6小时，信号高度集中在施莱姆管。在阿柏西普注射后24小时采集的2只眼中，一只眼中红色荧光信号强度降低，主要占据巩膜内静脉丛，另一只眼中则没有信号。在48小时时没有荧光信号，证实阿柏西普已完全清除。
在我们的大鼠模型中，注射后48小时可见阿柏西普从前房角完全清除。这一发现反驳了眼压升高与机械性阻塞之间可能存在联系的理论。在同一大鼠模型中，阿柏西普通过房角的排空时间与贝伐单抗的排空时间相当。
