他克莫司点眼治疗单纯疱疹病毒性盘状角膜基质炎的疗效及其对泪膜的影响
타극막사점안치료단순포진병독성반상각막기질염적료효급기대루막적영향
Efficacy of tacrolimus eyedrops topical application for herpes simplex disciform stromal keratitis and its influence on tear
  • 万方数据
    中华实验眼科杂志 중화실험안과잡지
    CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
    2015年 1期 60-65 ,共6页

    梁凌毅%林丽霞%刘祖国

    량릉의%림려하%류조국

    他克莫司/用法,剂量%免疫抑制剂/用法,剂量%疱疹角膜炎/治疗%用药方案%疗效 他剋莫司/用法,劑量%免疫抑製劑/用法,劑量%皰疹角膜炎/治療%用藥方案%療效
    타극막사/용법,제량%면역억제제/용법,제량%포진각막염/치료%용약방안%료효
    Tacrolimus/administration & dosage%Immunosuppressive agents/administration & dosage%Keratitis,herpetic/therapy%Drug administration schedul%Treatment outcome
    背景 单纯疱疹病毒(HSV)盘状角膜基质炎是一种抗原和抗体在角膜基质层内引起的T细胞介导的迟发型超敏反应,以往的疗法是糖皮质激素联合抗病毒药物的局部应用,但不能耐受糖皮质激素的患者治疗效果不佳,且糖皮质激素的局部应用存在严重的不良反应.FK506滴眼液具有糖皮质激素的免疫抑制和抗炎作用,又不存在糖皮质激素的不良反应,但FK506滴眼液对HSV盘状角膜基质炎的疗效研究很少.目的 探讨他克莫司滴眼液治疗HSV盘状角膜基质炎的疗效、安全性及其对泪膜的影响.方法 在中山大学中山眼科中心伦理委员会批准和患者知情同意下,采用系列病例观察研究设计,纳入2011年6月至2012年6月在中山大学中山眼科中心确诊为活动期HSV盘状角膜基质炎的患者18例18眼,采用质量分数0.05％他克莫司滴眼液局部应用联合抗病毒药物局部和全身应用的方案进行治疗,平均用药(56.0±7.9)d,分别于治疗前、治疗后1个月、2个月以及停药时进行裂隙灯显微镜检查、基础泪液分泌试验(SⅠt)、泪膜破裂时间(BUT)测定和角膜荧光素染色检查,动态观察0.05％他克莫司滴眼液对HSV盘状角膜基质炎的疗效、不良反应及其对泪膜稳定性的影响.结果 患者治疗后角膜厚度开始下降的平均时间为(8.3±2.5)d,角膜水肿消失的平均时间为(25.3±11.5)d,水肿消退最慢的2例患者为糖皮质激素治疗无效者.治疗前、治疗后1个月、治疗后2个月及停药时角膜荧光素染色评分分别为4(6,2)、1(2,1)、1(1,0)和0(1,0),差异有统计学意义(H=39.90,P＜0.001),患者治疗后各时间点间角膜荧光素染色评分均明显低于治疗前,差异均有统计学意义(均P＜0.01);患者治疗前后各时间点的SⅠt值分别为(6.78±1.90)、(7.39±3.53)、(8.06±2.92)和(8.11 ±3.05) mm/5 min,不同时间点SⅠt值的差异无统计学意义(F=0.90,P=0.43);患者治疗前后各时间点BUT值分别为(0.39±0.50)、(1.11±0.90)、(2.00±1.08)和(3.39±0.92)s,各时间点的总体差异有统计学意义(F=34.54,P＜0.01),治疗后各时间点的BUT值较治疗前均明显增加,差异均有统计学意义(均P＜0.00l).18例患者中2例于停药后2个月和5个月复发,再次按相同方案治疗后治愈.治疗期间未发生眼压升高或继发感染等并发症.结论 眼局部应用他克莫司滴眼液联合抗病毒治疗可减轻HSV盘状角膜炎患者的角膜水肿并促进泪膜修复,并可用于糖皮质激素局部应用无效者或有糖皮质激素禁忌证患者.
    배경 단순포진병독(HSV)반상각막기질염시일충항원화항체재각막기질층내인기적T세포개도적지발형초민반응,이왕적요법시당피질격소연합항병독약물적국부응용,단불능내수당피질격소적환자치료효과불가,차당피질격소적국부응용존재엄중적불량반응.FK506적안액구유당피질격소적면역억제화항염작용,우불존재당피질격소적불량반응,단FK506적안액대HSV반상각막기질염적료효연구흔소.목적 탐토타극막사적안액치료HSV반상각막기질염적료효、안전성급기대루막적영향.방법 재중산대학중산안과중심윤리위원회비준화환자지정동의하,채용계렬병례관찰연구설계,납입2011년6월지2012년6월재중산대학중산안과중심학진위활동기HSV반상각막기질염적환자18례18안,채용질량분수0.05％타극막사적안액국부응용연합항병독약물국부화전신응용적방안진행치료,평균용약(56.0±7.9)d,분별우치료전、치료후1개월、2개월이급정약시진행렬극등현미경검사、기출루액분비시험(SⅠt)、루막파렬시간(BUT)측정화각막형광소염색검사,동태관찰0.05％타극막사적안액대HSV반상각막기질염적료효、불량반응급기대루막은정성적영향.결과 환자치료후각막후도개시하강적평균시간위(8.3±2.5)d,각막수종소실적평균시간위(25.3±11.5)d,수종소퇴최만적2례환자위당피질격소치료무효자.치료전、치료후1개월、치료후2개월급정약시각막형광소염색평분분별위4(6,2)、1(2,1)、1(1,0)화0(1,0),차이유통계학의의(H=39.90,P＜0.001),환자치료후각시간점간각막형광소염색평분균명현저우치료전,차이균유통계학의의(균P＜0.01);환자치료전후각시간점적SⅠt치분별위(6.78±1.90)、(7.39±3.53)、(8.06±2.92)화(8.11 ±3.05) mm/5 min,불동시간점SⅠt치적차이무통계학의의(F=0.90,P=0.43);환자치료전후각시간점BUT치분별위(0.39±0.50)、(1.11±0.90)、(2.00±1.08)화(3.39±0.92)s,각시간점적총체차이유통계학의의(F=34.54,P＜0.01),치료후각시간점적BUT치교치료전균명현증가,차이균유통계학의의(균P＜0.00l).18례환자중2례우정약후2개월화5개월복발,재차안상동방안치료후치유.치료기간미발생안압승고혹계발감염등병발증.결론 안국부응용타극막사적안액연합항병독치료가감경HSV반상각막염환자적각막수종병촉진루막수복,병가용우당피질격소국부응용무효자혹유당피질격소금기증환자.
    Background Herpes simplex virus (HSV) disciform stromal keratitis is a T cell-mediated delayed-type hypersensitivity of corneal stroma.The treatment of HSV disciform stromal keratitis is the combination of glucocorticoid and antiviral drug before.However,the therapy is limited for intolerantble patients to glucocorticoid.In addition,the adverse reactions following usage of glucocorticoid can not be ignored.FKS06 solution is proved to has the immunosuppressive and antiinflammatory acttions with less side effects than glucocorticoid drug.But the study on the application of FK506 solution in treatment of HSV disciform stromal keratitis is lack.Objective This prospective clinical trail was to evaluate the efficacy of topical tacrolimus for HSV disciform stromal keratitis and its safety.Methods A prospective study was performed on 18 consecutive cases (18 eyes) who were diagnosed as active HSV disciform stromal keratitis from June 2011 to June 2012 in Zhongshan Ophthalmic Center under the approval of the Ethic Committee of Zhongshan Ophthalmic Center and informed consent of the patients,including 3 patients with refractory to prior steroid eyedrops.All patients received a combination topical tacrolimus eyedrops 4 times per day with topical and systemic anti-viral therapy for mean (56.0±7.9) days.Corneal thickness by slit lamp biomicroscope,visual acuity,intraocular pressure,corneal fluorescein staining,Schirmer Ⅰ test (S Ⅰ t) and tear breakup time (BUT) were performed on the patients before and 1 month,2 months after treatment and at the drug withdrawal to assess the treating efficacy of FK506,and the adverse reactions of eyes were recorded.Results Corneal edema was alleviated in (8.3 ± 2.5) days after treatment in all the patients and returned to normality in (25.3±11.5) days.Corneal edema of 2 eyes with refractory to previous steroid eyedrops showed a slower recovery procedure than that of the others.Corneal fluorescence staining scores were 4 (6,2),1 (2,1),1 (1,0) and 0 (1,0) before and 1 month,2 months and at drug withdrawal,respectively,with a significant difference among the four time points (H=39.90,P＜0.001),and the scores were significantly lower after treatment than before (all at P＜0.01).The S Ⅰ t values were (6.78±1.90),(7.39±3.53),(8.06±2.92) and (8.11±3.05) mm/5 min,respectively in the 4 time points,without statistically significant difference among various time points (F =0.94,P =0.43).The BUT values were (0.39 ± 0.50),(1.11 ± 0.90),(2.00 ± 1.08) and (3.39 ± 0.92) seconds,respectively,showing a significant difference among the 4 time points (F=34.54,P＜0.01) and had the increased values after treatment of FK506.Recurrence was seen in 2 eyes in 2 months and 5 months after cessation of tacrolimus.However,the eyes were healed after a second round regimen.No elevation of intraocular pressure and secondary infection were found in the patients during the treatment and follow-up period.Conclusions The combination therapy of tacrolimus with antiviral drug is effective and safe for HSV disciform stromal keratitis by alleviating corneal edema and promoting the rehabilitation of tear film.
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