Saravia Mario, Zapata Gustavo, Ferraiolo Paula, Racca Lourdes, Berra Alejandro
Laboratory of Investigation in Ophthalmology, Department of Pathology, School of Medicine, University of Buenos Aires, J.E. Uriburu 950, Buenos Aires, Argentina.
Graefes Arch Clin Exp Ophthalmol. 2009 Oct;247(10):1409-16. doi: 10.1007/s00417-009-1101-y. Epub 2009 Aug 5.
To determine the efficacy of bevacizumab (Avastin), an anti-VEGF monoclonal antibody, administrated via subconjunctival injection as a corneal anti-angiogenic treatment.
Right corneas of rabbits were infected with herpes simplex virus type 1, KOS strain. On day 13 post-infection (p.i.), animals were treated subconjunctivally (sc) with a single 10-microl dose (25 microg/microl) of bevacizumab (group A) or with the same volume of an isotype monoclonal antibody, as negative control (group B). All animals were observed clinically on days 2, 5, 7, 14, 21, and 28 p.i., and two corneas each day were obtained for histological assessment and viral titration.
Viral replication was observed no longer than 5 days after infection. By day 7 a dense neutrophil invasion of the cornea was detected, which significantly increased while herpetic stromal keratitis progressed in severity. Positive outcomes observed following the treatment with bevacizumab, compared to control, included: (1) Total involution of neovascularization, (2) reduction in disease severity, (3) improved corneal translucency, (4) absence of scarring, (5) preservation of corneal thickness, (6) no neutrophil infiltration of the cornea.
Subconjunctival administration of bevacizumab induced involution of new vessels, abolished inflammatory response, and resulted in return of corneal function. Furthermore, bevacizumab is a novel approach for the treatment of herpetic stromal keratitis.
确定通过结膜下注射给予抗血管内皮生长因子（VEGF）单克隆抗体贝伐单抗（阿瓦斯汀）作为角膜抗血管生成治疗的疗效。
用1型单纯疱疹病毒KOS株感染兔的右眼角膜。感染后第13天（p.i.），给动物结膜下（sc）注射单剂量10微升（25微克/微升）的贝伐单抗（A组）或相同体积的同型单克隆抗体作为阴性对照（B组）。在感染后第2、5、7、14、21和28天对所有动物进行临床观察，每天取两只角膜进行组织学评估和病毒滴定。
感染后观察到病毒复制不超过5天。到第7天，检测到角膜有密集的中性粒细胞浸润，随着疱疹性基质性角膜炎严重程度的进展，浸润显著增加。与对照组相比，贝伐单抗治疗后观察到的阳性结果包括：（1）新生血管完全消退，（2）疾病严重程度降低，（3）角膜透明度提高，（4）无瘢痕形成，（5）角膜厚度保持，（6）角膜无中性粒细胞浸润。
结膜下注射贝伐单抗可诱导新生血管消退，消除炎症反应，并使角膜功能恢复。此外，贝伐单抗是治疗疱疹性基质性角膜炎的一种新方法。
