[The effectiveness and safety of topical 0.1% tacrolimus after high-risk penetrating keratoplasty].

Objective: To observe the effectiveness and safety of topical 0.1% tacrolimus(FK506) as immunosuppressant in high-risk penetrating corneal transplantation to prevent the immune rejection and to compare the outcomes with topical 1% Cyclosporin A (CsA). Methods: The study consists of 49 patients (50 eyes), who were fitted with the high-risk corneal transplantation standard and undergone the penetrating keratoplasty(PKP) or combined operation in Beijing Tongren hospital between March 2015 to September. With the time sequence, the patients were divided into observation group (FK506 group) and the control group (CsA group). The observation group included 9 females and 16 males with an average age of 57.8±14.8. Twenty-four patients were in the control group (25 eyes), including 10 females and 14 males, with an average age of (45.1±16.2). Observation group was treated with topical 0.1% tacrolimus, and the control group treated with topical 1%CsA. Both groups' treatment combined glucocorticoid as well. Two groups had 1 year follow-up observation. The incidence of rejection was compared by statistical methods of Cox regression. The adverse reactions were graded and compared using Mann-Whitney U test. Results: After one year, 22 cases of the observation group and 23 cases of the control group were accomplished all observations. The rejection rate was 4.54% in observation group and 27.23% in control group. The difference between the groups was statistically significant (χ(2)=4.291, P=0.038). Control group had high rejection rate. Besides, there was no severe side effects happened in both groups. After 1 month after surgery, 36.4% of the observation group showed mild corneal edema. The ratio of mild to moderate corneal edema in the control group was 26.1% and 8.7%. Three months after surgery, 4.5% of the observation group showed mild corneal edema, while 13.0% and 13.0% of the control group was found mild to moderate corneal edema. Six months after surgery, 4.5% of the observation group showed moderate corneal edema. The ratio of mild, moderate to severe corneal edema in the control group was 17.4%, 17.4% and 8.7%. The degree of corneal edema in the control group was more serious in three monthes(Z=-2.770, -2.018, -2.941, P<0.05). The differences in both monthes were statistically significant. Mild neovascularization occurred in the 13.6% of observation group. Mild to severe neovascularization occurred in the 13.0%, 4.3%, and 4.3% control groups. The degree of neovascularization in the control group was higher than that in the observation group(Z=-3.221, P=0.001). The differences in both months were statistically significant. Mild to moderate neovascularization occurred in the 18.2% and 9.1% of observation group. Mild to extremely severe neovascularization occurred in the 17.4%, 26.1%, 4.3% and 4.3% control groups. The degree of neovascularization in the control group was higher than that in the observation group(Z=-1.988, P=0.047).The differences in both monthes were statistically significant. Conclusions: Both 0.1% tacrolimus and 1% cyclosporine A are safe and effective in reducing the rejection after high-risk corneal transplantation. (Chin J Ophthalmol, 2019, 55: 419-427).目的： 探讨0.1%他克莫司滴眼液预防高危穿透性角膜移植术后免疫排斥反应的有效性和安全性。 方法： 病例对照研究。收集2015年3至9月北京同仁眼科中心角膜病专科拟行穿透性角膜移植术的符合高危角膜移植标准的患者49例（50只眼），按先后顺序分为观察组25例（25只眼），其中女性9例，男性16例，年龄（57.8±14.8）岁。对照组24例（25只眼），其中女性10例，男性14例，平均年龄（45.1±16.2）岁。观察组患者使用0.1%他克莫司滴眼液治疗，对照组使用1%环孢素A滴眼液治疗。两组患者均随访1年，主要观察指标有视力、眼压、结膜充血水肿、角膜上皮缺损、角膜水肿、基质混浊、新生血管植入。免疫排斥反应的发生率采用Cox回归方法进行比较；不良反应按等级进行评分，采用Mann-Whitney U检验比较其分布情况。 结果： 观察组共22例完成随访，1年观察期内1例（4.54%）发生免疫排斥反应；对照组共23例完成随访，免疫排斥反应6例（27.23%）。两组排斥率的差异有统计学意义（χ(2)=4.291，P=0.038）。术后1个月，观察组有8例（36.4%）轻度角膜水肿，对照组有6例（26.1%）轻度及2例（8.7%）中度角膜水肿，两组差异有统计学意义（Z=-2.770，P=0.006）。术后3个月，观察组有1例（4.5%）轻度角膜水肿，对照组轻度及中度角膜水肿各3例（13.0%），两组差异有统计学意义（Z=-2.018，P=0.004）。术后6个月，观察组有1例（4.5%）轻度角膜水肿，对照组轻度及中度角膜水肿各4例（17.4%），重度2例（8.7%），差异有统计学意义（Z=-2.941，P=0.003）。术后1个月，观察组出现轻度新生血管者3例（13.6%），对照组轻度、中度及重度新生血管者共5例（21.7%），差异有统计学意义（Z=-3.221，P=0.001）。术后6个月，观察组轻度及中度新生血管者6例（27.3%），对照组出现轻度、中度、重度及极重度新生血管者12例（52.2%），差异有统计学意义（Z=-1.988，P=0.047）。两组患者的视力变化未见差异。观察组有4例患者眼压升高，对照组3例眼压升高。观察组与对照组均各出现1例角膜上皮缺损严重需佩戴治疗性角膜接触镜治疗。 结论： 局部使用0.1%他克莫司和1%环孢素A滴眼液预防高危角膜移植术后的免疫排斥反应方面均安全、有效；使用0.1%他克莫司滴眼液的患者免疫排斥反应发生率低，同时发生不良反应较少。（中华眼科杂志，2019，55：419-427）.