Clinical Study Of Keluoxin Capsule In The Treatment Of Non-Proliferative Diabetic Retinopathy

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,phase Ⅱa clinical trial.From May 2014 to December 2016,according to the International Clinical Classification Criteria for Diabetic Retinopathy(DR)in 2002,the patients diagnosed with moderate to severe NPDR who received Keroxin treatment in Central Theater General Hospital,Affiliated Eye Hospital of 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,retinal capillary non-perfusion area(RNP)and Early Treatment Diabetic Retinopathy Study(ETDRS)Diabetic Retinopathy Severity Scale(DRSS)grading changes 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 by χ2 test.Result: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 and 81.4 ± 6.3 letters,respectively.CMT were 249.5± 32.1 and 258.9 ± 22.2 μm,respectively.TMV were 8.79 ± 1.09 and 9.96±1.16 mm3,respectively.Retinal vascular leakage areas were 7.69 ± 10.63,10.45 ± 7.65 mm2,respectively.RNP were 2.48 ± 5.74,10.63 ± 20.06 mm2,respectively.There were 11(29.7%,11/37)and 4(28.6%,4/14)eyes with diabetic macular edema(DME),respectively.After 24 weeks treatment,BCVA in moderate and severe NPDR group increased by 1.3±5.2 and 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 and 269.8 ± 57.2 μm,respectively.There were no significant differences compared with baseline(t=-0.567,-0.925;P>0.05).TMV were 8.95±1.31,10.09±1.32 mm3,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 mm2,respectively.There were no significant differences compared with baseline(t=0.168,0.983;P>0.05).RNP were 3.01 ± 6.47,10.36 ± 19.57 mm2,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(χ2=11.919,4.571;P=0.001,0.033).The proportions of patients treated with keluoxin capsule with a 2step or more improvement in DRSS score at week 24 were 3.9%,with a 1-step or more improvement in DRSS score were 3.9%.There is no significant change were 72.6%.Only 1 eye progressed to 1-step in DRSS score(1.9%).Conclusion:Keluoxin capsules can stabilize or improve BCVA and DRSS score.Its safety and efficacy have been confirmed in this study.However,larger and longerterm prospective controlled clinical trials are desirable to confirm the efficacy of Keluoxin capsule in the treatment of NPDR scientifically.