小牛血去蛋白提取物治疗机械性角膜上皮损伤的临床疗效分析

Efficacy of protein-free calf blood extract for mechanical corneal epithelial defects in human eyes

目的探讨小牛血去蛋白提取物与重组人表皮生长因子衍生物对机械性角膜上皮损伤的临床疗效。方法采用平行、阳性对照设计及多中心、随机、双盲方法。将2005年4至11月在复旦大学附属眼耳鼻喉科医院、上海交通大学医学院附属新华医院、浙江大学医学院附属第一医院、浙江大学医学院附属第二医院、青岛市立医院诊断为机械性角膜上皮损伤的240例（240只眼）患者以随机数字表法分入两组，即小牛血去蛋白提取物组（120只眼）与重组人表皮生长因子衍生物组（120只眼）。两组分别滴用20％小牛血去蛋白提取物滴眼液和5000IU／ml重组人表皮生长因子衍生物滴眼液，每天给药4次，每次1滴，疗程14d。用药前和用药后3、7、14d分别对症状、体征观察进行综合评分以及评价其安全性。采用非劣性检验、配对t检验、Wilcoxon秩和检验法、卡方检验、校正卡方检验、Fisher精确检验、方差分析及CMH）（2法等方法对数据进行统计学分析。结果小牛血去蛋白提取物组与重组人表皮生长因子衍生物组有效率的组间比较差异无统计学意义（用药后：3d x^2=1．5677，P=0．4566；7d x^2=1．7152，P=0．4242；14d x^2=3．0814，P=0．2142）。用药后第3天小牛血去蛋白提取物组症状体征综合评分下降幅度为（6．009±3．030）分，重组人表皮生长因子衍生物组为（5．177±2．582）分，差异有统计学意义（t=2．2367，P=0．0263）。用药前、后视力比较，两组之间无明显差别；烧灼感、眼痒方面的比较，两组之间差异无统计学意义（用药后烧灼感：3d x^2=0．4394，P=0．932；7d x^2=1．4710，P=0．479；14d x^2=2．1875，P=0．335。用药后眼痒：3d x^2=2．1045，P=0．349；7d x^2=2．0192，P=0．364；14d x^2=0．6863，P=0．407）。舒适性方面，用药后3d小牛血去蛋白提取物组较好，两者之间比较差异有统计学意义（x^2=6．626，P=0．0100）；但是，用药后7、14d眼部舒适性两组之间比较差异无统计学意义（用药后：7d x^2=7．8106，P=0．050；14d x^2=5．5278，P=0．063）。结论小牛血去蛋白提取物滴眼液能够有效治疗机械性角膜上皮损伤，起效时间短，安全性较好。

Objective To evaluate the clinical efficacy between protein-free calf blood extract eye drops and recombinant human epidermal growth factor （rhEGF） eye drops for mechanical corneal epithelial defects in human eyes. Methods A multi-center, randomized and double-blind study with a parallel, positive-control designation was carried out from April to November in 2005 at Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University, Xinhua Hospital of Shanghai Jiaotong University, the First Hospital of Zhejiang University, the Second Hospital of Zhejiang University and Qingdao Municipal Hospital. 240 patients（240 eyes）with confirmed diagnosis of corneal epithelial defects at that six hospitals were enrolled in this study and were randomly arranged into two groups in average. One group （ 120 eyes） were treated by 20% protein-free calf blood extract eye drops which was defined as the experimental group while the other （120 eyes） by 5000 IU/ml recombinant human epidermal growth factor （rhEGF） eye drops as the positive control group. The drug was delivered in both groups 4 times per day, one drop each time in the 14 days duration. The symptoms and signs were scored and the safety was evaluated on the pre-delivery day,the third post-delivery day （day 3） ,day 7 and day 14. The variants in the study were tested for the different efficacy and safety between the two drugs using non-inferiority test, paired t-test, Wilcoxon signedrank test, chi-square test, continuity correction chi-square test, Fisher＇s exact probabilities, analysis of variance, Cochran-Mantel-Haenszel chi-square test and so on. The criterion for statistical significance was P 〈 0. 05. Results There was no significant difference in efficacy between the protein-free calf blood extract group and the recombinant human epidermal growth factor group （ day 3 ： x^2 = 1. 5677, P = 0. 4566, day 7 ： x^2 = 1. 7152 ,P = 0. 4242, day 14 ：x^2 = 3. 0814, P = 0. 2142 ）. The total scores of symptoms and signs in experimental group had a obvious descending （6. 009 ± 3. 030） compared with the positive control group with a descending of （5. 177 ± 2. 582）, which reached the significant level （ t = 2. 2367, P = 0. 0263 ） . Ocular local stimulates and general side effect were not observed within the treatment course. There was no significant difference between the two groups in the comparison of pre-and post-therapy visual acuity. The difference was not significant when comparing the uncomfortable feelings, including eye burning and eye itching（eye burning：day 3：x^2 =0.4394,P =0.932,day 7：x^2 = 1.4710,P =0. 479,day 14：x^2=2. 1875, P=0. 335, and eye itching：day 3：x^2 =2. 1045,P = 0. 349,day 7：x^2 =2.0192,P =0. 364,day 14：x^2 = 0. 6863 ,P =0. 407）. And the positive control group gave priority to the experimental group in comfortability. A better comfortableness was reported in the protein-free calf blood extract group on the third day postdilivery （x^2 = 6. 626,P = 0. 0100）. However, no obvious difference was examined on day 7 and day 14 postdilivery. Conclusion Protein-free calf blood extract eye drops has confirmed efficacy, good safety, quick effect and better comfortableness.