不同浓度ZKY001滴眼液治疗原发性翼状胬肉切除术后角膜上皮缺损的疗效  

Efficacy of different concentrations of ZKY001 eyedrops in the treatment of corneal epithelial defect after primary pterygium excision

作　　者：高华 祝磊[2] 徐建江[3] 陶黎明[4] 董燕玲 陈陆霞[6] 晋秀明[7] 李贵刚[8] 吴护平 赵平 陈蔚[11] 李小羿 史伟云 Gao Hua;Zhu Lei;Xu Jianjiang;Tao Liming;Dong Yanling;Chen Luxia;Jin Xiuming;Li Guigang;Wu Huping;Zhao Ping;Chen Wei;Li Xiaoyi;Shi Weiyun(Eye Institute of Shandong First Medical University,Eye Hospital of Shandong First Medical University,Shandong Eye Hospital,State Key Laboratory Cultivation Base,Shandong Provincial Key Laboratory of Ophthalmology,School of Ophthalmology,Shandong First Medical University,Jinan 250021,Shandong Province,China;Henan Provincial People's Hospital,Henan Eye Hospital,Zhengzhou 450000,Henan Province,China;Eye&ENT Hospital of Fudan University,NHC/Chinese Academy of Medical Sciences Key Laboratory of Myopia,Shanghai 200031,China;Department of Ophthalmology,the Second Hospital of Anhui Medical University,Hefei 230601,Anhui Province,China;Qingdao Eye Hospital of Shandong First Medical University,Qingdao 266071,Shandong Province,China;Tianjin Eye Hospital,Nankai University Affiliated Eye Hospital,Clinical College of Ophthalmology of Tianjin Medical University,Tianjin Eye Institute,Tianjin Key Laboratory of Ophthalmology and Visual Science,Tianjin 300020,China;Eye Center,Second Affiliated Hospital of Zhejiang University School of Medicine,Zhejiang University Eye Hospital,Hangzhou 310009,Zhejiang Province,China;Department of Ophthalmology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China;Xiamen Eye Center of Xiamen University,Xiamen 361001,Fujian Province,China;Shenyang Aier Eye Hospital,Shenyang 110003,Liaoning Province,China;Ningbo Eye Hospital,Wenzhou Medical University Ningbo Eye Hospital,Ningbo 315000,Zhejiang Province,China;Zhaoke(Guangzhou)Ophthalmology Pharmaceutical Ltd.,Guangzhou 510060,Guangdong Province,China)

机构地区：[1]山东第一医科大学附属眼科研究所、山东第一医科大学附属眼科医院、山东省眼科医院山东省眼科学重点实验室-省部共建国家重点实验室培育基地、山东第一医科大学眼科学院,山东省济南市250021 [2]河南省人民医院河南省立眼科医院,河南省郑州市450000 [3]复旦大学附属眼耳鼻喉科医院国家卫生健康委员会/中国医学科学院近视眼重点实验室,上海市200031 [4]安徽医科大学第二附属医院眼科,安徽省合肥市230601 [5]山东第一医科大学附属青岛眼科医院,山东省青岛市266071 [6]天津市眼科医院南开大学附属眼科医院、天津医科大学眼科临床学院、天津市眼科研究所、天津市眼科学与视觉科学重点实验室,天津市300020 [7]浙江大学医学院附属第二医院眼科中心、浙江大学眼科医院,浙江省杭州市310009 [8]华中科技大学同济医学院附属同济医院眼科,湖北省武汉市430030 [9]厦门大学附属厦门眼科中心,福建省厦门市361001 [10]沈阳爱尔眼视光医院,辽宁省沈阳市110003 [11]宁波市眼科医院、温州医科大学宁波市眼科医院,浙江省315000 [12]兆科(广州)眼科药物有限公司,广东省广州市510060

出　　处：《国际眼科杂志》2024年第12期1888-1894,共7页International Eye Science

基　　金：广州市南沙区科技计划项目资助(No.2021ZD005);国家自然科学基金资助项目(No.82271058);山东省重点研发计划(重大科技创新工程)项目(No.2022CXGC010505)。

摘　　要：目的:探究不同浓度ZKY001滴眼液治疗原发性翼状胬肉切除术后角膜上皮缺损的有效性和安全性。方法:本研究为多中心、随机、双盲、安慰剂对照的Ⅱ期临床研究。选取2022-03-15/11-14全国12家三甲医院原发性翼状胬肉术后患者,采用区组随机化的方法按照1∶1∶1比例将患者178例178眼随机分为三组:安慰剂组(给予ZKY001模拟滴眼液治疗)60例60眼,0.002%ZKY001滴眼液组59例59眼,0.004%ZKY001滴眼液组59例59眼。各组患者接受研究药物每次1滴,每天4次,使用4 d。观察各组患者在不同时间点的角膜上皮缺损面积较基线改善百分比,角膜上皮缺损区首次完全愈合时间,角膜上皮缺损首次愈合人数,眼部不适(眼痛、异物感、畏光、流泪)等视觉模拟量表评分变化。结果:三组患者角膜上皮缺损首次愈合时间、在不同的随访点三组角膜上皮缺损面积较基线改善百分比、首次愈合人数百分比均无差异(均P>0.05)。但从数值上看,0.002%ZKY001组(67.87±21.688 h)、0.004%ZKY001组(61.48±22.091 h)角膜上皮缺损首次愈合时间较安慰剂组短(68.85±20.851 h)。在D1上午,0.004%ZKY001滴眼液组的角膜缺损面积较基线改善的百分比与安慰剂组的数值差值达到最大,且在后续的随访点保持着数值差值的优势。试验组在不同随访点的角膜上皮缺损区首次愈合人数较安慰剂组多。眼部不适改善方面:试验组较安慰剂组的VAS评分总分值降低多,以异物感评分、疼痛感评分降低为主,在D3时0.004%ZKY001滴眼液组对异物感的改善明显优于其他两组(P<0.017)。安全性方面:总体不良事件发生率低(9.0%),且三组间相似。结论:原发性翼状胬肉术后使用ZKY001滴眼液可改善角膜上皮缺损修复,改善术后因角膜上皮缺损引起的不适症状且安全性良好。AIM:To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS:This was a multicenter,randomized,double-blinded,placebo-controlled phase II clinical trial.From March 15,2022 to November 14,2022,patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China.Using block randomization,178 patients(178 eyes)were randomly assigned to 3 groups in a 1∶1∶1 ratio:0.002%ZKY001 group(n=59),0.004%ZKY001 group(n=59),and placebo group(n=60,receiving ZKY001 sham eye drops).Subjects in each group received 1 drop of the study drug 4 times per day for 4 d.The percentage of CED area recovery from baseline,the first complete healing time of CED area,the number of first complete healing cases of CED,and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain,foreign body sensation,tearing and photophobia were observed.RESULTS:In terms of improvement in CED,there were no statistically significant differences among the three groups including the first healing time of CED,the percentage improvement in CED area compared to baseline,and the percentage of first healing cases at different follow-up visits(all P>0.05).Numerically,the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002%ZKY001 group,61.48±22.091 h for the 0.004%ZKY001 group,and 68.85±20.851 h for the placebo group).On D1 morning,the percentage improvement in CED area compared to baseline was maximally different from the placebo group,and the numerical difference advantage was maintained at subsequent follow-up visits.The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group.In terms of improvement in ocular discomfort,the total VAS scores were lower in the test groups compared to the placebo group,mainly due to reductions in foreign body s

关 键 词：翼状胬肉切除术 ZKY001滴眼液 角膜上皮的缺损修复 缓解不适 有效性和安全性 

分 类 号：R779.6[医药卫生—眼科]