0.05％环孢素A滴眼液治疗干眼的有效性和安全性临床评价

摘要

背景 干眼是常见的眼表疾病,质量分数0.05％环孢素A是一种免疫抑制剂,国外的研究表明其对干眼具有治疗作用,但中国尚未批准将0.05％环孢素A滴眼液用于干眼治疗. 目的 研究0.05％环孢素A治疗干跟的有效性和安全性. 方法 采用随机、双盲、安慰剂平行对照的优效试验方法,纳入2010年10月至2011年2月在四川大学华西医院确诊的干眼患者40例40眼,采用随机卡片法将经筛选期、基线期以及再次核查后符合纳入标准的患者随机分为2个组,2个组患者均给予羟丙基甲基纤维素滴眼液点眼作为基础治疗,同时分别给予0.05％环孢素A滴眼液(Ⅱ)和环孢素A滴眼液(Ⅱ)溶媒点眼84 d.患者均于用药后(7±1)、(28±2)、(56±3)、(84±3)d以及停药后14 d进行复查,将用药前后眼部症状、体征以及干眼相关检查指标作为有效性评价指标,将用药前后视力的改变、用药后不适感、全身安全性以及不良事件作为安全性评价指标,评估0.05％环孢素A滴眼液治疗干眼的有效性和安全性. 结果 治疗前后0.05％环孢素A滴眼液组和溶媒组的眼部症状评分、结膜充血评分、泪膜破裂时间(BUT)、Schirmer试验Ⅰ(SⅠ t)、角膜结膜染色总评分明显不同,差异均有统计学意义(均P＜0.01).0.05％环孢素A滴眼液组和溶媒组的临床总有效率分别为75％(15/20)和25％ (5/20),组间比较差异有统计学意义(P=0.000),0.05％环孢素A滴眼液组与溶媒组总有效率的差值的95％可信区间(CI)为30.80％ ～53.75％,证实0.05％环孢素A组较溶媒组的统计优效成立.治疗后84d2个组受试者视力的差异无统计学意义(P=0.890).大多数受试者用药后眼部无不适感,少数有轻中度不适.结论 0.05％环孢素A滴眼液(Ⅱ)对于治疗干眼有较好的疗效,并且具有良好的安全性.%Background Dry eye is a common disease worldwide.Cyclosporine A(CsA) is provided to be a immunosuppressive agent and is effective on dry eye.But in China,0.05％ CsA is not yet applied in dry eye treatment.Objective This study was to evaluate the efficacy and safety of 0.05％ CsA eye drops in the treatment of dry eye.Methods This was a randomized,double-blind,vehicle-controlled parallel group study.Forty eyes of 40 patients with moderate to severe dry eye were randomly divided into two groups,with the corresponding treatment of 0.05％ CsA eye drops or the vehicle emulsion.The patients in both the groups received non-preserved artificial tear.Symptoms and signs were observed before administration,(7±1),(28±2),(56±3),and (84±3) days and also 14 days after withdrawal.The clinical effective rate was considered as the primary outcome.The subjective assessment of the patients including total symptom scores and ocular surface disease index (OSDI) scores,Schirmer Ⅰ test (S Ⅰ t) with topical anaesthesia,tear film breakup time (BUT),rose Bengal and fluorescein staining scores were evaluated.The safety profile was evaluated by adverse events,visual acuity and ocular tolerance.Results At the end of this trial,the ocular symptoms scores,conjunctival hyperemia,BUT,S Ⅰ t and keratoconjunctiva staining scores of the two groups had statistically significant difference.The total effective rate of 0.05％ CsA treatment group was 75％ (15/20) and vehicle group was 25％ (5/20).There was a statistically significant difference between groups (P =0.000),and the 95％ confidence interval (C1) of the difference value of total effectiveness between the two groups was 30.80％-53.75％.At the end of this trial,there was no statistically significant difference in visual acuity distribution (P =0.890).No obvious discomfort was found in the patients received 0.05％ CsA eye drops.There were no adverse events during the follow-up duration.Conclusions 0.05％ CsA ophthalmic emulsion is an effective and safe treatment for dry eyes.