渴络欣胶囊治疗中重度非增生型糖尿病视网膜病变的初步临床应用研究

Preliminary clinical application of Keluoxin capsule for treatment of moderate and severe non-proliferative diabetic retinopathy

目的观察中药渴络欣胶囊治疗中重度非增生型糖尿病视网膜病变(NPDR)的安全性及有效性。方法多中心、非盲、单臂、Ⅱa期临床研究。研究对象为2014年5月至2016年12月于中部战区总医院、南昌大学附属眼科医院、中国中医科学院西苑医院、中国中医科学院眼科医院检查确诊并接受渴络欣药物治疗的中重度NPDR患者,并据此分为中度NPDR组、重度NPDR组。所有患者均行最佳矫正视力(BCVA)、彩色眼底照相、光相干断层扫描、荧光素眼底血管造影以及实验室检查。在原有控制糖尿病的治疗基础上,给予患者口服渴络欣胶囊治疗,连续24周。以治疗后24周末为疗效判定时间点。对比观察两组患者基线及治疗后24周末BCVA、黄斑中心凹视网膜厚度(CMT)、6 mm直径范围内黄斑视网膜体积(TMV)、视网膜血管渗漏面积、视网膜无灌注区(RNP)面积变化。组间连续变量比较行独立样本Mann-Whitney U检验;分类资料比较行χ^(2)检验。结果共计纳入NPDR患者60例60只眼,失访9例,最终纳入51例51只眼,其中中度NPDR组、重度NPDR组分别为37、14只眼。基线时,中度NPDR组、重度NPDR组患眼BCVA分别为(80.1±6.8)、(81.4±6.3)个字母;CMT分别为(249.5±32.1)、(258.9±22.2)μm;TMV分别为(8.79±1.09)、(8.95±1.31)mm^(3);视网膜血管渗漏面积分别为(7.69±10.63)、(10.45±7.65)mm^(2);RNP面积分别为(2.48±5.74)、(10.63±20.06)mm^(2);伴糖尿病黄斑水肿(DME)分别为11(29.7%,11/37)、4(28.6%,4/14)只眼。治疗后24周,中度NPDR组、重度NPDR组患眼BCVA分别提高(1.3±5.2)、(3.2±3.0)个字母;与基线时比较,重度NPDR组差异有统计学意义(t=-3.986,P=0.033)。CMT分别为(252.1±45.6)、(269.8±57.2)μm;与基线时比较,差异均无统计学意义(t=-0.567、-0.925,P>0.05)。TMV分别为(9.96±1.16)、(10.09±1.32)mm^(3);与基线时比较,差异均无统计学意义(t=-0.996、-1.304,P>0.05)。视网膜血管渗漏面积分别减小(0.19±6.90)、(1.98±7.52)mm^(2);与基线时比较,差异均无统计学意义(t=0.168、0.983,P>0.05)。RNP面积分别为(3.01±6.47)、(10.36±19.57)mm^(2);与基线时比较,差异均无统计学意义(t=-1.267、0.553,P>0.05)。伴DME分别为8(21.6%,8/37)、3(21.4%,3/14)只眼;与基线时比较,差异有统计学意义(χ^(2)=11.919、4.571,P=0.001、0.033)。结论渴络欣胶囊可稳定或改善中重度NPDR患眼BCVA、CMT、TMV、RNP面积,降低视网膜血管渗漏面积。

Objective To observe the safety and efficacy of Keluoxin capsules in the treatment of moderate to severe non-proliferative diabetic retinopathy(NPDR).Methods An open-label,multi-center,single-arm,phaseⅡa clinical trial.From May 2014 to December 2016,the patients diagnosed with moderate to severe NPDR who received Keroxin treatment in General Hospital of Central Theater Command,Affiliated Eye Hospital to Nanchang University,Xiyuan Hospital of China Academy of Chinese Medical Sciences,and Eye Hospital China Academy of Chinese Medical Sciences were divided into moderate NPDR group and severe NPDR group.The baseline data of the patients were obtained,best-corrected visual acuity(BCVA),optical coherence tomography,fundus fluorescein angiography and fundus photography were performed.On the basis of maintaining the original diabetes treatment,all patients took Keluoxin capsules orally for 24 weeks;24 weeks after treatment was used as the time point for evaluating the efficacy.BCVA letters,central macular thickness(CMT)and 6 mm diameter total macular volume(TMV),retinal vascular leakage area,and retinal non-perfusion(RNP)area within an average diameter of 6 mm were compared between the two groups at baseline and 24 weeks after treatment.Independent sample Mann-Whitney U test was used to compare continuous variables between groups.Categorical data were compared byχ^(2) test.Results A total of 60 NPDR patients and 60 eyes were included,9 cases were lost to follow-up,and 51 cases and 51 eyes were finally included,including 37 eyes in the moderate NPDR group and 14 eyes in the severe NPDR group,respectively.At baseline,BCVA in moderate NPDR group and severe NPDR group were(80.1±6.8),(81.4±6.3)letters,respectively.CMT were(249.5±32.1),(258.9±22.2)μm,respectively.TMV were(8.79±1.09),(8.95±1.31)mm^(3),respectively.Retinal vascular leakage areas were(7.69±10.63),(10.45±7.65)mm^(2),respectively.RNP area were(2.48±5.74),(10.63±20.06)mm^(2),respectively.There were 11(29.7%,11/37)and 4(28.6%,4/14)eyes with diabetic macular edema(DME),respectively;24 weeks after treatment,BCVA in moderate NPDR group and severe NPDR group increased by(1.3±5.2),(3.2±3.0)letters,respectively.Compared with baseline,there was a statistically significant difference in the severe NPDR group(t=-3.986,P=0.033).CMT were(252.1±45.6),(269.8±57.2)μm,respectively.There were no significant differences compared with baseline(t=-0.567,-0.925;P>0.05).TMV were(9.96±1.16),(10.09±1.32)mm^(3),respectively.There were no significant differences compared with baseline(t=-0.996,-1.304;P>0.05).Retinal vascular leakage area decreased(0.19±6.90),(1.98±7.52)mm^(2),respectively.There were no significant differences compared with baseline(t=0.168,0.983;P>0.05).RNP area were(3.01±6.47),(10.36±19.57)mm^(2),respectively.Compared with baseline,the differences were statistically significant(t=-1.267,0.553;P>0.05).There were 8(21.6%,8/37)and 3(21.4%,3/14)eyes with DME,respectively.Compared with baseline,the difference was statistically significant(χ^(2)=11.919,4.571;P=0.001,0.033).Conclusion Keluoxin capsules can stabilize or improve BCVA,CMT,TMV and RNP area in patients with moderate and severe NPDR,and reduce the area of retinal vascular leakage.