Antiscarring effect of intraoperative bevacizumab in experimental glaucoma filtration surgery

ABSTRACT Purpose: To determine the effects of bevacizumab and mitomycin C alone and in combination on intraocular pressure and the scarring process after modified glaucoma filtration surgery in rabbits. Methods: The rabbits underwent modified glaucoma filtration surgery and were allocated into three groups to receive intraoperative treatment with subconjunctival bevacizumab (group A), mitomycin C and subconjunctival bevacizumab (group B), or mitomycin C (group C). Intraocular pressure was measured immediately preoperatively and on postoperative days 8, 14, 17, 21, 26, and 30. The scarring process was assessed 30 days after surgery by tissue section using hematoxylin and eosin, Masson’s trichrome, and picrosirius. Expression of vascular endothelial growth factor (VEGF) was assessed by immunohistochemical analyses. All analyses were performed by a masked observer. Results: Animals in group A had higher intraocular pressure than those in groups B and C (p<0.01). Intraocular pressure did not differ significantly between groups B and C. The amount of fibrosis was similar with all stains used: group A had the highest level of fibrosis compared with groups B and C (p>0.05). There was less VEGF expression in group A than in groups B and C (p<0.01). Groups B and C did not differ in VEGF expression. Conclusion: Mean intraocular pressure and fibrosis were lower in animals receiving bevacizumab in combination with mitomycin C but did not differ from values in animals receiving mitomycin C alone. Inhibition of VEGF was greater when bevacizumab was used alone than when bevacizumab was combined with mitomycin C.

摘要 目的：探讨贝伐单抗（bevacizumab）与丝裂霉素C（mitomycin C）单独及联合应用，对兔改良青光眼滤过术后眼内压（intraocular pressure）及瘢痕形成过程的影响。方法：对接受改良青光眼滤过术的兔进行分组，术中分别予以结膜下注射贝伐单抗（A组）、丝裂霉素C联合结膜下注射贝伐单抗（B组），以及单纯丝裂霉素C（C组）。分别于术前即刻及术后第8、14、17、21、26、30天检测眼内压。术后30天，采用苏木精-伊红（hematoxylin and eosin）染色、马松三色（Masson’s trichrome）染色及天狼星红（picrosirius）染色对组织切片进行评估，以分析瘢痕形成情况；通过免疫组织化学分析检测血管内皮生长因子（VEGF）的表达水平。所有分析均由设盲观察者（masked observer）完成。结果：A组兔的眼内压显著高于B组与C组（p<0.01）；B组与C组的眼内压无显著差异。三种染色方式下纤维化程度的评估结果一致：A组纤维化程度最高，但与B、C组相比差异无统计学意义（p>0.05）。A组的VEGF表达水平低于B、C组（p<0.01）；B组与C组的VEGF表达水平无显著差异。结论：联合应用贝伐单抗与丝裂霉素C的实验动物，其平均眼内压及纤维化程度均低于单独使用贝伐单抗的动物，但与单独使用丝裂霉素C的动物相比无显著差异。单独使用贝伐单抗时，对VEGF的抑制效果较二者联合应用时更为显著。