Cornea Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Cornea Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, New Jersey.
Ophthalmology. 2022 Aug;129(8):865-879. doi: 10.1016/j.ophtha.2022.03.024. Epub 2022 Mar 28.
To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation.
Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil.
Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.
Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks.
The 52-week endothelial immune rejection rate.
Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis.
In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.
评估局部（结膜下和局部）贝伐单抗（阿瓦斯汀）治疗行血管化高危角膜移植患者的疗效。
在美国、印度和巴西的 5 个临床中心进行的一项初步、前瞻性、随机、双盲、安慰剂对照临床试验。
年龄> 18 岁、行高危穿透性角膜移植术的患者，定义为角膜新生血管（NV）在 1 个或多个象限中距角膜缘≥2mm，或在先前失败的移植物中角膜 NV 延伸至移植物-宿主交界处。
患者在手术时随机接受结膜下贝伐单抗（2.5mg/0.1ml）或安慰剂，随后接受 4 次/天的局部贝伐单抗（10mg/ml）或局部安慰剂治疗，共 4 周。
52 周内皮免疫排斥率。
92 例患者随机分为贝伐单抗组（n=48）或对照组（n=44）。贝伐单抗组的 52 周内皮排斥率为 10%，对照组为 19%（P=0.20）。事后分析，在主要研究点的延长随访中，贝伐单抗组的内皮排斥率为 3%，对照组为 38%（P=0.003）。贝伐单抗治疗的 Cox 回归分析后发现，危险比为 0.15（95%置信区间，0.03-0.65，P=0.01）。
在血管化高危角膜移植患者中，与对照组相比，贝伐单抗治疗组在 1 年内内皮排斥率无统计学差异。本研究可能因效力不足而无法检测到治疗组之间的差异，综合来看，我们的数据表明，在当前试验设计中，贝伐单抗对内皮排斥有积极但尚未（显著）的作用。
