真菌性角膜溃疡患者穿透角膜移植术前后泪液(1,3)-β-D-葡聚糖的变化

摘要

背景 穿透角膜移植术(PKP)近年来已成为治疗真菌性角膜溃疡的有效方法,但是术后糖皮质激素的使用时机目前暂无定论.研究发现真菌性角膜溃疡患者泪液中(1,3)-β-D-葡聚糖的质量浓度明显高于正常. 目的 检测真菌性角膜溃疡患者行PKP术前及术后泪液中(1,3)-β-D-葡聚糖的质量浓度变化,探讨其对术后应用抗真菌药物的持续时间和糖皮质激素类药物应用的时机. 方法 采用病例观察研究设计,收集2011年8月至2012年12月在青岛大学附属医院就诊的真菌性角膜溃疡行PKP的患者20例20眼,以患者的自身对侧眼作为对照组,分别于术前ld及术后1、7、14、21、28 d收集患者泪液各50μl,用G实验法检测泪液中(1,3)-β-D-葡聚糖质量浓度. 结果 对照组,实验组术前ld,术后1、7、14、21和28 d泪液中(1,3)-β-D-葡聚糖的质量浓度分别为(14.67±3.84)、(1 861.66±196.17)、(927.71±155.82)、(392.30±71.22)、(179.60±40.47)、(40.20±12.46)、(15.12± 1.80) mg/L,组间总体比较差异有统计学意义(F=883.45,P=0.00).随着术后时间的延长,术眼泪液中(1,3)-β-D-葡聚糖质量浓度逐渐下降,各时间点与前一时间点间比较差异均有统计学意义(t'=13.84、t=16.67、t'=11.02、t'=13.97、t'=-8.45,均P=0.00),术后28 d泪液中(1,3)-β-D-葡聚糖质量浓度接近对照组,差异无统计学意义(P=0.64).术后28 d内18例患眼感染无复发,2例患眼分别于术后第5天和第6天感染复发,泪液中(1,3)-β-D-葡聚糖质量浓度分别为2 350.24 mg/L和1 992.82 mg/L.结论 真菌性角膜溃疡患者PKP术后泪液中(1,3)-β-D-葡聚糖的质量浓度于术后28 d降至正常范围,提示真菌性角膜溃疡患者PKP术后抗真菌治疗至少需维持28 d,此时局部使用糖皮质激素抗排斥反应较为安全.%Background Penetrating keratoplasty (PKP) has become an effective method of treatment for fungal keratitis in recent years,but the application timing of glucocorticoids after PKP is still unclear.Literature reported that the concentration of tear (1,3)-β-D-glucan in fungal keratitis was significantly higher than that in normal.Objective This study was to investigate the change of tear (1,3)-β-D-glucan before and after PKP in fungal keratitis and to explore the application duration of anti-fungal drugs and application timing of glucocorticoids.Methods This study protocol was approved by ethic committee of Affiliated Hospital of Qingdao University.A serial cases-observational study was performed from August,2011 to December,2012.Twenty eyes of 20 patients with fungal keratitis were collected in Affiliated Hospital of Qingdao University.PKP was performed in affected eyes,and the fellow health eyes served as controls.Tear of 50 μl was obtained in the controls on 1 day before operation and 1 day,7,14,21 and 28 days after operation to detect tear (1,3)-β-D-glucan levels.Results Tear (1,3)-β-D-glucan levels were (14.67±3.84)mg/L,(1 861.66±196.17) mg/L,(927.71±155.82)mg/L,(392.30±71.22)mg/L,(179.60±40.47) mg/L,(40.20± 12.46) mg/L and (15.12± 1.80) mg/L in the control group,preoperative 1 day,postoperative 1 day,7,14,21,28 days,respectively,showing a significant difference among various time points (F=883.45,P=0.00).Tear (1,3)-β3-D-glucan levels were gradually reduced with the lapse of the postoperative time,with significant differences between adjacent timepoints (t' =13.84,t =16.67,t' =11.02,t' =13.97,t' =-8.45,all at P=0.00).Tear (1,3)-β-D-glucan levels in postoperative 28 days came near that of normal control group,without significant difference between them (P =0.64).Fungal keratitis recurred in 2 eyes on the fifth and sixth day after operation,with the tear (1,3)-β-D-glucan levels of 2 350.24 mg/L and 1 992.82 mg/L,respectively.Conclusions The concentration of (1,3)-β-D-glucan in the tears increases in the eyes with fungal keratitis and drops to normal range at 28 days after PKP,indicating that the antifungal eyedrops should be applied until 4 weeks after PKP,and this is an optimal timing of using corticosteroid eyedrops to resist reject reaction.