摘要
目的比较0.05%环孢素与0.1%他克莫司滴眼液治疗慢性眼部移植物抗宿主病(oGVHD)后患者眼表干眼相关指标及泪液炎症因子的改变。方法采用随机对照研究方法,纳入2020年4月至2021年4月于北京大学第三医院眼科确诊为慢性oGVHD的患者60例60眼,采用随机数字表法将患者分为他克莫司组30例30眼和环孢素组30例30眼。他克莫司组主要采用0.1%他克莫司滴眼液点眼,2次/日;环孢素组采用0.05%环孢素滴眼液点眼,4次/日。此外,2个组患眼均采用0.1%氟米龙滴眼液2次/日、小牛血去蛋白提取物眼用凝胶3次/日、0.1%玻璃酸钠滴眼液8次/日点眼,进行抗炎和润滑治疗。用药后1个月随访并依据排除标准筛选患者,最终将他克莫司组21例21眼和环孢素组12例12眼纳入后续研究。分别于治疗前、治疗后1个月对患眼进行检查,主要评价指标包括眼表疾病指数(OSDI)问卷评分、角膜荧光素钠染色评分和泪膜破裂时间(BUT)。采用Luminex芯片法检测患眼治疗前后泪液中白细胞介素(IL)-6、IL-8、IL-17、表皮生长因子(EGF)和肿瘤坏死因子-α(TNF-α)的质量浓度并进行组间比较。结果他克莫司组和环孢素组治疗前后OSDI差值分别为0.4(-5.6,21.5)和27.2(4.6,45.0),环孢素组OSDI改善程度明显优于他克莫司组,差异有统计学意义(Z=-2.547,P=0.009)。他克莫司组和环孢素组治疗前后角膜荧光素钠染色评分差值分别为5.0(2.5,10.0)分和3.5(-0.5,13.8)分,BUT差值分别为0.0(-3.0,0.0)s和-1.5(-3.0,0.0)s,组间比较差异均无统计学意义(Z=-0.526、-0.804,均P>0.05)。他克莫司组与环孢素组治疗前后IL-6、IL-8、IL-17、EGF和TNF-α表达量差值比较,差异均无统计学意义(Z=-0.487、-0.112、-0.412、-1.085、-1.198,均P>0.05)。结论2种药物治疗慢性oGVHD后,患者泪液中各因子含量的改变程度均未见显著差异。慢性oGVHD患者应用0.05%环孢素滴眼液治疗可能比0.1%他克莫司滴眼液有更好的舒适度。
Objective To compare ocular surface dry eye-related indexes and tear cytokine level changes in chronic ocular graft-versus-host disease(oGVHD)patients after receiving topical treatment of 0.05%cyclosporine or 0.1%tacrolimus eye drops.Methods A randomized controlled study was conducted.A total of 60 chronic oGVHD patients(60 eyes)were recruited at Beijing University Third Hospital from April 2020 to April 2021.The patients were divided into tacrolimus group and cyclosporine group by a random number table,with 30 patients(30 eyes)in each group.Patients in tacrolimus group used 0.1%tacrolimus eye drops(twice a day)and patients in cyclosporine group used 0.05%cyclosporine eye drops(4 times a day).Additionally,0.1%flumetholon(twice a day),deproteinized calf blood extract(3 times a day),and 0.1%sodium hyaluronate eye drops(8 times a day)were applied for anti-inflammation and lubrication in both groups.Patients were screened according to exclusion criteria after 1-month treatment.Eventually,21 patients(21 eyes)in tacrolimus group and 12 patients(12 eyes)in cyclosporine group were included for further study.Patients were examined before and 1 month after treatment.The primary evaluation indexes included Ocular Surface Disease Index(OSDI),corneal fluorescein staining scores and tear film break-up time(BUT).Expressions of interleukin(IL)-6,IL-8,IL-17,epidermal growth factor(EGF),and tumor necrosis factor-α(TNF-α)in tears were detected before and after treatment using Luminex chip.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital(No.M2020489).Written informed consent was obtained from each subject before any medical examination.Results The OSDI differences between before and after treatment were 0.4(-5.6,2.5)in tacrolimus group and 27.2(4.6,45.0)in cyclosporine group,and the OSDI improvement was significantly greater in cyclosporine group than in tacrolimus group(Z=-2.547,P=0.009).The differences of corneal fluorescein staining scores and BUT between before and after treatment were 5.0(2.5,10.0)scores and 3.5(-0.5,13.8)seconds in tacrolimus group,0.0(-3.0,0.0)scores and-1.5(-3.0,0.0)seconds in cyclosporine group,respectively,with no significantly difference between both groups(Z=-0.526,-0.804;both at P>0.05).The differences of IL-6,IL-8,IL-17,EGF and TNF-αexpressions between before and after treatment in tacrolimus group and cyclosporine group were not significantly different(Z=-0.487,-0.112,-0.412,-1.085,-1.198;all at P>0.05).Conclusions Altered levels of all tested cytokines in oGVHD tears are of no significant differences between tacrolimus and cyclos porine treatment.In addition,0.05%cyclosporine eye drops may be more comfortable than 1%tacrolimus for chronic oGVHD patients.
作者
马骄
申展
胡博浩
赵英涵
刘姝婉
吴蓉
彭荣梅
洪晶
Ma Jiao;Shen Zhan;Hu Bohao;Zhao Yinghan;Liu Shuwan;Wu Rong;Peng Rongmei;Hong Jing(Department of Ophthalmology,Peking University Third Hospital,Beijing Key Laboratory of Restoration of Damaged Ocular Nerve,Beijing 100191,China;Department of Ophthalmology,Peking University Shenzhen Hospital,Shenzhen 518000,China)
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2023年第10期980-984,共5页
Chinese Journal Of Experimental Ophthalmology
基金
国家自然科学基金项目(81970768)
北京白求恩公益基金项目(BJ-GY2021003J)。
关键词
移植物抗宿主病
干眼
泪液
细胞因子
环孢素
他克莫司
Graft vs host disease
Dry eye syndromes
Tears
Cytokines
Cyclosporine
Tacrolimus
