Clinical Research Of Chinese Medicinals Combined With Conbercept In The Treatment Of Diabetic Macular Edema

Diabetic macular edema is a major cause of visual loss in individuals with diabetes.The pathogenesis of diabetic macular edema is multifactorial and complex.At present,the main treatment are laser photocoagulation,vitreoretinal surgery,intraocular injection of drugs,and so on,all have a certain effect.The anti VEGF therapy revolutionized the treatment pattern and efficacy of DME patients.However,the efficacy of anti VEGF drugs is short and need to be injected repeatedly.With the continuous exploration and application of traditional chinese medicine in this field,its advantages and curative effects are gradually emerging.Chinese medicine treatment pays much attention to the holistic concept,combined with anti VEGF drugs,so that many patients benefit.However,there is still lack of evidence-based medical evidence of standardized design.Visual function evaluation in DME mainly adopts best corrected visual acuity,but it only represents the function of macular fovea "dot".Microperimetry provides a more comprehensive information for quantitative assessment of macular function.In this study,a randomized controlled double blind trial was designed to study the effect of Chinese medicinals on DME treatment,and preliminarily discuss the effect of Chinese medicinals on retina sensitivity and fixation stability.The relationship between visual function and structural features of DME was analyzed.Objective:1.To evaluate the efficacy and safety of Chinese medicinals combined with conbercept in the treatment of DME,verify the role of Chinese medicinals in the treatment of DME.2.To evaluate the relationship between visual functional parameters(MAIA microperimetry parameters and BCVA)and morphological structure characteristics(OCT)of macular area in DME.3.To preliminary evaluate retinal sensitivity and the fixation alterations in patients with diabetic macular edema(DME)under Chinese medicinals combined intravitreal conbercept therapy.Methods:1.It is a randomized double blind prospective study.The 156 patients with diabetic macular edema were randomly divided into two groups(Chinese medicinals combined with conbercept group and placebo combined with conbercept group).The two groups both were treated with intravitreal conbercept one time.The two groups were taken oral Chinese medicinals or placebo for 3 months respectively.The best corrected visual acuity,central retinal thickness and traditional Chinese medicine syndrome were observed before and after treatment 1 week,1 month,2 month and 3month.And the ophthalmic and combined use of drugs were recorded.The effectiveness of the two groups in the treatment DME was evaluated with the best corrected visual acuity as the main therapeutic index.The changes of liver and kidney function before and after treatment are used as an index to evaluate the safety of Chinese medicinals.2.This prospective,non-controlled,open study included 61 eyes of 38 consecutive patients with DME.All patients underwent best corrected visual acuity(BCVA)measurement,MAIA microperimetry,and SD-OCT.DME morphology,including central retinal thickness(CRT)and central retinal volume(CRV);integrity of the external limiting membrane(ELM)and photoreceptor inner segment/outer segment(IS/OS)junction;and deposition of hard macular exudates were assessed within a 1,000-μm central subfield area.The MAIA microperimetric parameters evaluated were average threshold(AT)-retinal sensitivity,macular integrity index(MI),fixation points within a circle of radius 1°(P1)and 2°(P2),and the bivariate contour ellipse area considering 63%and 95%of the fixation points(A63 and A95,respectively).3.It is a randomized double blind prospective study.Each group included 20 cases of DME patients,the same as the first part.Using microperimetry and OCT,observed 3 months,before and after the treatment,a monthly record of the best corrected visual acuity,central retinal thickness,retinal sensitivity,fixation characteristics(P1,P2).Results:1.After treatment,the number of BCVA letters in the two groups was significantly higher than that before the treatment.The Increased number of letters in the treatment group was significantly higher than that of the control group at 1 months and 3 months.The median letters number of BCVA improvement in treatment group in the 1 week,1 month,2 month and 3 month were 5(2),10(5),6(1),7.5(0.75)respectively.The median letters number of BCVA improvement in control group for 1 weeks,1 month,2 month and 3 month were 6(3),6(1),4(1.5),3(-1)respectively.In two groups,difference in median letters number of BCVA increased from baseline in for 1 weeks(P=0.901),1 month(P=0.022),2month(P=0.053),and 3 month(P=0.020).After treatment,the two groups of CRT were significantly lower than the baseline.The decrease of CRT in the treatment group was more significant than that of the control group at 2 months and 3 months.Central retinal thickness in two groups compared with the baseline was declined in 7 days,1 month,2 month and 3 month.In treatment group were 131.25±19.5μm,154.57±19.77μm,101.47±23.18μm,97.15±23.89μm respectively;In control group were 88.9±16.41μm,118.67±18.21μm,39.82±16.27μm,2.5±5.49μm.The treatment and control group BCVA increased more than 5 letters at 3 months respectively 64.3%,34.9%(P=0.006);more than 10 letters were 40.5%and 20.9%(P=0.042),there were significant differences between two groups.The treatment group in improving the symptoms of traditional Chinese medicine is obviously better than control group.In the two groups,the liver and kidney function were rechecked on 3 month end during the period of taking Chinese medicinals or placebo.There was no difference in two groups.2.MI was significantly bigger in eyes with ELM or IS/OS defects than in eyes with intact ELM and IS/OS.Compared with the intact IS/OS group the total retinal sensitivity,central retinal sensitivity and P2 were lower and logMAR BCVA,A63,A95 and CRT were higher in defective group and the difference was significant.Compared with the intact ELM group central retinal sensitivity was lower and logMAR BCVA and CRT were higher in defective group and the difference was significant.These parameters showed no statistical difference in the presence or absence of hard macular exudate deposition.CRV was not statistically different in the presence or absence of the integrity of ELM and IS/OS and hard macular exudate deposition.At the center and nasal and temporal sides of the fovea,significant negative correlations were observed between retinal thickness and the AT of the corresponding area.At the inferior and superior sides of the fovea,no correlations were observed between retinal thickness and the AT of the corresponding area.In the intact IS/OS group,significant negative correlations were observed between CRT and the center AT.Little to no association was observed between sensitivity and thickness when the IS/OS layer was absent.Multiple linear regression analysis revealed that IS/OS integrity was an independent factor affecting MI.3.The retinal sensitivity increased slightly after treatment in the two groups,but there was no significant difference between the two groups and over the course of treatment in control group.P1 and P2 in the two groups increased significantly after treatment.The increase of P1 in the treatment group was significantly higher than that in the control group at 2 months and 3 months.The increase of P2 in the treatment group was significantly higher than that of the control group at 3 months.Conclusion:1.The efficacy of Chinese medicinals combined with conbercept in the treatment DME was better than that single conbercept.The combined treatment of Chinese medicinals could improve the BCVA,reduce macular edema,delay the recurrence of macular edema,and improve patients’ systemic symptoms.It is safe and reliable.The combined treatment of Chinese medicinals did not increase the risk of liver and kidney damage.2.The visual function was correlated with the macular region structure in DME patients.The IS/OS junction and ELM integrity in the macular region were related to the maintenance of visual function.In intact IS/OS,the higher the CRT,the lower the BCVA and retinal sensitivity,and there is no correlation between CRT and BCVA,retinal sensitivity in defective IS/OS.The macular integrity index could be used to evaluate the macular visual function.3.Intravitreal conbercept could improve the fixation stability in DME patients,Chinese medicinals was conducive to improve and maintain fixation stability.Microperimetry is effective for quantitative evaluation visual function effect of DME intervention.Fixation stability might be an important parameter for assessing early visual function changes.