| ObjectiveTo make a summary on the status and problems of clinical trial outcomes and suggest outcomes setting advice consulting international outcomes status of Chinese medicine for diabetic retinopathy(DR). To assess the effect and safety of Chinese herbal medicines (CHMs) with syndrome differentiation and treatment for treating diabetic retinopathy(DR).MethodsWe searched for randomized clinical trials (RCTs) of Chinese medicine for DR in The Chinese Biomedical Literature Database(SinoMed), China National Knowledge Infrastructure (CNKI), Chinese VIP Information(VIP), Chinese Academic Conference Papers Database and Chinese Dissertation Database(Wangfang), PubMed, Cochrane Library from their inception to December,2015. We also searched for systematic reviews (SRs) for DR in Cochrane Library from their inception to December,2015. A data extraction form was used to extract data. Two authors independently screened for inclusion and extracted data, which inconsistent content decided by the third author.The risk of bias table which recommended by Cochrane handbook was used to evaluated methodological quality. SPSS 17.0 and RevMan 5.3 software were used to performed data analysis. Heterogeneity test were conducted using I2 test. Subgroup analysis was conducted depend on type of Chinese medicine and syndrome differentiation and treatment.According to GRADE system, GRADEpro3.6 software produced summary of finding table to evaluate evidence. Using SAS 8.2 software, Egger linear regression method and Macaskill’s test evaluate publication bias quantitatively.ResultsCHMs for DR included 93 RCTs 6776 participants and totally reported 11 outcomes and these outcomes were not divided into primary outcomes or secondary outcomes. The outcomes reported frequency from high to low were, in order, composite outcome (68trials, 4772 participants), vision (35 trials,2136 participants), fundus (24 trials,1828 participants), blood rheology(18 trials,1588 participants), glucose (13 trials,972 participants), adverse reactions (7 trials,594 participants), blood lipid (7 trails,363 participants), field of vision(6 trials,310 participants), visual electrophysiological examination (4 trials,288 participants), DR disease progression (2 trails,166 participants) and the quality of life (1 trial,119 participants). There were 68 trials(73.1%) reported composite outcome indicators, and 22 trials reported composite outcome indicators with reference standards, including 5 different reference standards. DR therapeutic systematic review(SR) were searched 5 papers published by Cochrane Library.The outcomes of five SRs were all divided into primary outcomes and secondary outcomes. These primary outcomes included progression of disease, end point events, vision and occurrence of disease. The secondary outcomes included progression of disease, end point events, vision, occurrence of disease, adverse events, quality of life, cost and fundus oculi.CHMs for DR included 56 RCTs 4104 participants. Three trials were assessed as low risk of bias and the other trials were high.34 meta-analysis in 37 trials have been performed. And 20 meta-analysis had statistical significant difference, they included that,whole blood high shear viscosity, whole blood low shear viscosity, plasma viscosity, fibrinogen and OPs total amplitude in CHMs plus conventional medicine versus conventional medicine; increased number of people vision, and vision is greater than the number 0.5 or 4.7 in CHMs plus laser photocoagulation treatment versus laser photocoagulation treatment;vision,micro hemangioma, hemorrhage absorption and effusion absorption time in CHMs plus western medicine plus laser photocoagulation treatment compared with laser photocoagulation treatment plus western medicine; retinal capillary perfusion area and scope of capillary leakage in CHMs plus conventional medicine versus placebo plus conventional medicine; whole blood high shear viscosity, triglyceride and total cholesterol in CHMs versus western medicine; increased number of people vision, fibrinogen, glycosylated hemoglobin and triglyceride in CHMs plus conventional medicine versus western medicine plus conventional medicine.Two meta-analysis which were evaluated moderate by GRADE showed that CHMs plus conventional medicine was superior to placebo plus conventional medicine in retinal capillary non-perfusion zone area (n=159; 3trials; MD,-0.08; 95%CI,-0.14 to-0.02) and capillary leak scope (n=159; 3trials; MD.-0.11; 95%CI,-0.18 to-0.03). And the rest of them were evaluated low or very low by GRADE. One of 56 included trials reported one participant occurred stroke and trial researcher thought which had nothing to do with trial drug, No serious adverse events were found in other trials.CHMs with syndrome differentiation and treatment for DR included 16 RCTs 3612 participants. Two trials were assessed as low risk of bias and the other trials were high. Eight trials had 15 meta-analysis and 3 of them had statistical significant difference. Compared CHMs plus conventional medicine with western medicine plus conventional medicine, low cut whole blood viscosity (n=106; 2trials; MD,1.88; 95%CI,-2.13 to-1.63; obstruction of collaterals by blood stasis) had statistical significance difference. Compared CHMs plus conventional medicine with placebo plus conventional medicine, retinal capillary non-perfusion zone area(n=47; 2trials; MD,-0.19; 95% CI,-0.34 to-0.04) and capillary leak scope (n=47; 2trials; MD,-0.15; 95% CI,-0.25 to-0.06) had statistical significance difference in deficiency of qi and yin and obstruction of collaterals by blood stasis.Three meta-analysis used Egger’s linear regression method and Macaskill’s test for quantitative evaluation showed no publication bias.No serious adverse events were found..ConclusionsThere are still large gaps between the choice of outcomes of clinical trails of Chinese medicine for DR and the international main trend. We suggest that conducting clinical researches about DR could consult international outcomes of common concerned and report primary outcomes and secondary outcomes respectively.Some CHMs and CHMs with syndrome differentiation and treatment showed potential effects on decreasing retinal capillary non-perfusion zone area capillary leak scope, and were not related with serious adverse effects. However, the findings should be interpreted with caution due to the small sample of the included trials and substantial heterogeneities of CHMs. |
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