0.05％他克莫司滴眼液治疗难治性免疫相关角膜溃疡的疗效及安全性研究  

Safety and efficacy of 0.05% tacrolimus eye drops for refractory ulcerative keratitis

作　　者：祝磊[1] 王丽娅[1] 张俊杰[1] 王璐璐[1] 栗占荣[1] 余晓菲[1] 李金[1] 

机构地区：[1]河南省眼科研究所河南省立眼科医院,郑州450003

出　　处：《中华实验眼科杂志》2015年第9期823-827,共5页Chinese Journal Of Experimental Ophthalmology

摘　　要：背景 难治性免疫相关角膜溃疡的局部药物治疗难以奏效,全身使用糖皮质激素和免疫抑制剂有产生严重不良反应的可能.研究表明他克莫司局部用药可以抑制局部的免疫性炎症,但目前没有关于质量分数0.05％他克莫司滴眼剂治疗难治性免疫相关角膜溃疡疗效和安全性的研究. 目的 研究0.05％他克莫司滴眼液点眼治疗难治性免疫相关角膜溃疡的疗效及安全性. 方法 采用观察性研究方法,对2010年7月至2014年9月于河南省立眼科医院用0.05％他克莫司滴眼液治疗的难治性免疫相关角膜溃疡患者17例21眼的疗效进行评估,其中男11例14眼,女6例7眼;平均年龄52岁.患者中11例未发现全身疾病,免疫学检测未见异常;6例有全身免疫性疾病,包括Wegener肉芽肿1例,风湿性关节炎4例,溃疡性肠炎1例,全身免疫性疾病经内科治疗病情已控制.单眼发病者13例,双眼发病者4例.病灶大于3个象限者2例2眼,2个象限以下者15例19眼.患者均经局部质量分数1％环孢素A和糖皮质激素治疗后角膜溃疡不愈或持续进展.采用0.05％他克莫司滴眼液点眼,根据病情调整用药剂量,分别于治疗前、治疗后1周及1、3、6、12和24个月裂隙灯显微镜下动态观察角膜溃疡的病灶变化,采用激光扫描共焦显微镜HRT-Ⅲ检查角膜病灶区炎性细胞密度的变化,评价0.05％他克莫司滴眼液的疗效.治疗期间观察和记录用药后眼部的不良反应,定期应用化学发光微粒子免疫法检测患者的血药质量浓度,实验室检查包括患者血常规、血糖水平和肝肾功能,评价药物的安全性.结果 本组患者治疗疗程为8 ～ 24个月,平均18.1个月.9眼治疗12个月,12眼治疗24个月.裂隙灯显微镜检查可见治疗后1个月15例19眼角膜溃疡面积缩小,2例2眼因溃疡进展而行板层角膜移植术,术后继续给予0.05％他克莫司滴眼液治疗;治疗后3个月角膜溃疡愈合;治疗后6个月病灶部�Background Local medical treatment of refractory immunologic keratitis is unsuccessful,and systemic steroids and immunosuppressive agents could cause severe side-effects.Tacrolimus is a potent immunosuppressive drug,it has been proved that topical application of tacrolimus could reduce immunologic inflammation.The safety and efficacy of 0.05% tacrolimus eye drops for refractory immunologic keratitis has not been described.Objective This study was to evaluate efficacy and safety of 0.05% tacrolimus eye drops for refractory ulcerative keratitis.Methods A retrospective study was performed.Twenty-one eyes of 17 patients with refractory immunologic keratitis,which had uncontrolled inflammation despite initially treatment including topical steroids and 1% cyclosporine A,were enrolled,including 11 males and 6 females,with the mean ages of 52 years.Infectious ulcer was excluded by laboratory tests.No systemic disease was found in 11 patients,and Wegener＆#39;s granulomatosis,rheumatoid arthritis and ulcerative colitis were seen in 1 patient,4 patients and 1 patient respectively before presentation and they were all in remission under conventional systemic therapy.Four patients got binocularly involved and thirteen patients were monocularly involved.Of the 21 eyes,2 eyes with ulcer were ≥ 3 quarters of the limbus,and 19 eyes with ulcer were ≤ 2 quarters.All patients were treated with 0.05% tacrolimus eyedrops after discontinuing cyclosporine A.The dosage was adjusted according to the severity of inflammation and was gradually tapered when improvement occurred.The corneal lesions were examined under the slit lamp microscope and Heidelberg HRT3 Rostock Cornea Module regularly,and inflammatory cell infiltrations were analyzed with Cell Count（R） software （Heidelberg Engineering GmbH）.The safety variables were monitored regularly,including adverse response of eye,tacrolimus blood concentrations measured by chemiluminescent microparticle immunoassay （CMIA） and laboratory examinations of blood routine,blood gluc

关 键 词：角膜溃疡/药物疗法 滴眼剂 他克莫司/治疗 他克莫司/不良反应 共焦显微镜 治疗效果 

分 类 号：R772.21[医药卫生—眼科]