Unit of Ophthalmology, School of Clinical Sciences, University of Liverpool, Liverpool, UK.
Retina. 2010 Jul-Aug;30(7):1012-6. doi: 10.1097/IAE.0b013e3181cb463a.
The purpose of this study was to determine the histopathologic characteristics of bevacizumab-treated human proliferative diabetic retinopathy (PDR) membranes with particular regard to membrane vasculature as a step toward addressing the effects of the drug on PDR membranes. Intravitreous injection of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, has recently been advocated as an adjunct in surgery for PDR. In this context, a clinically observed decrease in PDR epiretinal membrane vascularity (vascular regression) occurs from 24 hours to 48 hours after injection, but the exact mechanisms of drug action are unknown.
A consecutive series of seven PDR membrane specimens that had been removed sequentially from seven bevacizumab-treated patients were studied retrospectively. The membrane specimens were examined using light microscopic methods, including immunohistochemistry.
Five of the seven membranes were clinically avascular (one contained "ghost" vessels) and did not hemorrhage during excision. Of these 5 specimens, which included 1 removed 7 days after a total of 6 intravitreous injections of 1.25 mg bevacizumab, 4 contained histologically detectable capillaries (1 did not). These blood vessels were lined by endothelial cells as determined by immunohistochemistry for the endothelial markers CD31 and CD34. The two remaining membranes were clinically and histologically still vascularized despite bevacizumab treatment. All the specimens also contained smooth muscle actin-containing fibroblastic cells within the collagenous stroma.
The findings do not support the concept that the clinical phenomenon of vascular regression in PDR membranes after bevacizumab injection in the vitreous is resulting from obliteration of the membrane blood vessels. Another mechanism appears to be involved in at least some patients, possibly a vasoconstrictive response. Such a mechanism might explain reversal of the effects of bevacizumab that has been reported after this treatment.
本研究旨在确定贝伐单抗治疗的增生性糖尿病视网膜病变（PDR）膜的组织病理学特征，特别是针对膜血管，以期了解药物对 PDR 膜的影响。玻璃体内注射贝伐单抗（一种抗血管内皮生长因子的单克隆抗体）最近被提倡作为 PDR 手术的辅助手段。在此背景下，注射后 24 至 48 小时，PDR 视网膜前膜血管密度（血管消退）出现临床观察到的下降，但确切的药物作用机制尚不清楚。
对连续 7 例接受贝伐单抗治疗的患者先后切除的 7 例 PDR 膜标本进行回顾性研究。使用光镜方法，包括免疫组织化学方法，对膜标本进行了检查。
7 个膜标本中有 5 个临床无血管（1 个包含“幽灵”血管），在切除过程中未出血。在这 5 个标本中，有 1 个标本在总共 6 次玻璃体内注射 1.25 毫克贝伐单抗 7 天后取出，包含组织学上可检测到的毛细血管（1 个没有）。这些血管通过免疫组织化学检测内皮标志物 CD31 和 CD34 被确定为由内皮细胞组成。尽管接受了贝伐单抗治疗，但其余 2 个膜标本在临床上和组织学上仍然是血管化的。所有标本还在胶原基质中含有平滑肌肌动蛋白阳性的成纤维细胞。
这些发现不支持贝伐单抗玻璃体注射后 PDR 膜中血管消退的临床现象是由于膜血管闭塞的概念。另一种机制似乎至少在一些患者中涉及，可能是血管收缩反应。这种机制可能解释了在这种治疗后报道的贝伐单抗作用的逆转。
