Clinical Study Of Compound Anisodine Injection In The Treatment Of Chronic CSC And The Drug Effect Exploration

Objective:To study the efficacy,safety and possible mechanism of compound anisodine?CA?injection in the treatment of chronic central serous chorioretinopathy.Methods:A non-randomized concurrent control study.Patients with chronic serous chorioretinopathy were collected.According to the inclusion criteria and exclusion criteria,the patients were divided into two groups:CA injection combined with oral conventional drug therapy group and simple oral conventional drug treatment group.By observing the best corrected visual acuity?BCVA?,OCT and OCTA images of the two groups after 3 and 6 months treatment and using ImageJ software,the best corrected visual acuity?BCVA?,the central choroidal thickness?CCT?,the area of subretinal fluid?SRF?,the vessel density of the retinal superficial capillaries layers?SCL?,the deep capillaries layers?DCL?and the Choriocapillaries layer?CCL?in the macula were tested and compared with baseline in two groups.In vitro,ARPE-19 cells were cultured and the concentration gradient of compound anisodine?CA?and cobalt chloride?CoCl₂?was set up.The best safe concentration of CA and the hypoxia stimulation concentration of CoCl₂ were selected by MTT colorimetry.The effects of CA on the proliferation of ARPE-19 cells induced by CoCl₂ were detected by MTT colorimetry and JC-1 staining.Results:10 patients?11 eyes?were treated with oral conventional drugs,and 17patients?18 eyes?were treated with CA injection combined with oral conventional drug therapy.There was no significant difference in baseline between the two groups.The improvement of BCVA in the treatment group was significantly higher than that in the control group in 3 months and 6 months compared with the baseline?P<0.01?.At 6 months,the area of SRF in the two groups were both decreased comparing with baseline.However,the decreased area of SRF in the treatment group was sustaining during 6 months.The change of CCF in the treatment group was no different from that in the control group after 3 and 6 months treatment?P>0.05?.The vessel density of the DCL and the CCL at 6 months after treatment in two groups was significantly higher than that of the baseline,and there was a significant difference between the two groups?P<0.05?.In vivro,the results of MTT test showed that when the concentration of compound anisodine?CA?injection was higher than 15%?P<0.01?and the concentration of CoCl₂ was higher than 400uM?P<0.05?,the cell proliferation was obviously inhibited.Finally,we decided that the safe concentration of CA and CoCl₂ are 6%and 600uM,respectively.The cell proliferation of CA after CoCl₂ stimulated group,and the CA and CoCl₂ simultaneously stimulated group were significantly higher than that of the single CoCl₂ stimulation group?P<0.001,P<0.01?,and the mitochondrial membrane potential of the CA and CoCl₂ simultaneously stimulated group was significantly higher than that of the single CoCl₂ group.Conclusion:The BCVA of CA injection combined with oral conventional drug therapy was significantly improved in the treatment of CSC for 3 months and 6months.The results show that CA injection can promote the sustaining absorption of SRF and increase vessel density in the DCL and CCL after 6 months treatment.Thus,we consider that CA injection combined with conventional drug therapy can relieve the DCL and choroidal ischemic state of chronic CSC so that the BCVA of patients with chronic CSC can be improved effectively.The safety of CA injection was confirmed by no adverse events in treatment group.According to the results of cell experiments,CA injection has a protective and therapeutic effect on the hypoxia induced by cobalt chloride in the retinal pigment epithelial?RPE?cells during the safe concentration.