Effectiveness and safety of traditional Chinese medicine for diabetic retinopathy: A systematic review and network meta-analysis of randomized clinical trials

Table 1 Basic characteristics of included randomized controlled trials

Ref.	Sample size	Random method	Interventions		Period of treatment	Age	Outcomes	Adverse reactions
	C/E		C	E		C/E		C/E
Men[16], 2020	40/40	TRD	CT + Calcium Dobesilate	C + XST	8 wk	67.46 ± 2.52/63.12 ± 2.21	1, 2, 3, 4	-
Bai[17], 2016	38/38	-	CT + Calcium Dobesilate	C + XST	24 wk	51.08 ± 4.73/50.63 ± 5.51	1, 2, 7	3/2
An[18], 2021	30/30	-	Calcium Dobesilate	C + XST	20 wk	69.51 ± 5.19/70.32 ± 5.39	1, 2	-
Yan and Song[19], 2020	46/46	TRD	Calcium Dobesilate	C + XST	12 wk	47.4 ± 4.6/48.5 ± 4.9	1, 7	22/8
Li[20], 2021	20/20	-	Calcium Dobesilate	C + XST	20 wk	59.67 ± 1.78/58.51 ± 1.31	1, 3	-
Jin[21], 2020	40/40	-	Calcium Dobesilate	C + XST	20 wk	66.12 ± 3.45/66.58 ± 3.16	2, 3	-
Wu[22], 2015	50/50	TRD	CT	C + XST	12 wk	54.1 ± 6.6/54.6 ± 6.2	1	-
Qu[23], 2018	35/35	-	CT + Calcium Dobesilate	C + XST	20 wk	59.7 ± 6.3/60.4 ± 7.2	1	-
Sui[24], 2017	47/49	-	CT + Calcium Dobesilate	C + XST	4 wk	-	1	-
Jiang et al[25], 2019	46/46	-	Calcium Dobesilate	C + XST	20 wk	58.72 ± 2.20/58.69 ± 2.15	1, 2, 4	-
Zhu et al[26], 2016	48/48	-	CT	C + XST	12 wk	56.38 ± 12.19/56.15 ± 12.21	2	-
Sun[27], 2021	18/18	-	CT	C + XST	12 wk	61.38 ± 3.69/62.47 ± 3.01	1	-
Liu et al[28], 2018	45/45	TRD	CT + Calcium Dobesilate	C + XST	12 wk	48.56 ± 7.64/48.34 ± 6.49	1	-
Li[29], 2019	49/49	TRD	CT + Calcium Dobesilate	C + XST	12 wk	66.41 ± 4.11/66.82 ± 4.03	1, 2, 4	-
Xiao[30], 2016	110/110	-	CT + Calcium Dobesilate	C + XST	12 wk	50.2 ± 6.4/49.5 ± 5.9	1, 7	0/0
Chen[31], 2019	39/39	-	Calcium Dobesilate	C + XST	12 wk	58.17 ± 3.82/59.34 ± 3.27	1, 3, 4	-
Zhao[32], 2020	43/44	-	Calcium Dobesilate	C + XST	24 wk	53.71 ± 5.52/53.66 ± 5.49	3	-
An[33], 2020	35/35	-	Calcium Dobesilate	C + XST	12 wk	52.12 ± 15.76/51.17 ± 17.83	1, 4, 7	1/2
Zhang[34], 2019	19/19	-	Calcium Dobesilate	C + XST	8 wk	51.86 ± 1.92/53.28 ± 2.64	1, 7	0/0
Wei et al[35], 2017	34/34	TRD	CT	C + XST	35 wk	62.94 ± 3.48/61.31 ± 3.54	1, 3, 4, 7	0/0
Meng et al[36], 2012	38/40	-	CT + Calcium Dobesilate	C + XST	24 wk	49.2 ± 7.8/48.8 ± 6.7	1	-
Zhu and Sui[37], 2022	76/76	TRD	CT + Calcium Dobesilate	C + XST	12 wk	55.89 ± 4.17/55.94 ± 4.13	1, 2, 3, 7	12/13
Li[38], 2017	33/33	-	Calcium Dobesilate	C + XST	12 wk	-	2	-
Wang et al[39], 2020	42/44	TRD	CT + Calcium Dobesilate	C + XST	20 wk	68.35 ± 6.82/69.52 ± 7.11	1, 3, 7	4/3
Hu[40], 2017	30/30	-	Calcium Dobesilate	C + XST	20 wk	55.30 ± 2.15/55.67 ± 2.08	1, 3, 7	0/0
Xu and Ru[41], 2020	46/46	-	Calcium Dobesilate	C + XST	12 wk	52.3 ± 3.2/52.1 ± 3.6	1, 3	-
Wang[42], 2016	38/38	-	Iodized Lecithin	C + QM	8 wk	43 ± 6/42 ± 5	1	-
Wang[43], 2018	44/44	TRD	Calcium Dobesilate	C + QM	12 wk	58.4 ± 7.5/57.8 ± 6.2	1, 7	12/5
Wang et al[44], 2020	32/32	-	Amlodipine besylate	C + QM	12 wk	38.94 ± 4.89/39.87 ± 5.13	1, 2	-
Chen[45], 2016	45/45	TRD	CT	C + QM	12 wk	62.05 ± 5.47/63.11 ± 5.64	1	-
Wang et al[46], 2015	38/41	-	Calcium Dobesilate	C + QM	24 wk	52.1 ± 5.6/52.5 ± 5.3	1, 2, 7	0/0
Sui et al[47], 2014	43/43	-	Calcium Dobesilate	C + QM	12 wk	50.53 ± 11.28/50.22 ± 14.82	1, 2, 5, 6, 7	0/0
Huang[48], 2017	63/63	-	CT + Calcium Dobesilate	C + QM	12 wk	55.9 ± 4.1/55.6 ± 4.2	1	-
Feng et al[49], 2016	41/42	Lottery -	Calcium Dobesilate	C + QM	12 wk	55.89 ± 6.13/55.26 ± 6.29	1, 2, 5, 6	-
Ge[50], 2018	53/53	-	CT + Calcium Dobesilate	C + QM	24 wk	50.87 ± 3.71/51.25 ± 3.64	1	-
Yan[51], 2020	38/46	Lottery	CT + Calcium Dobesilate	C + QM	8 wk	56.96 ± 4.59/56.65 ± 4.02	1, 2, 5, 6, 7	8/2
Meng et al[52], 2016	21/21	-	Calcium Dobesilate	C + QM	24 wk	-	1	-
Zhang et al[53], 2016	46/45	-	CT	C + QM	24 wk	-	1	-
Zhang[54], 2013	34/34	-	CT	C + QM	36 wk	-	1	-
Wu et al[55], 2022	50/50	Lottery	Pancreatic Kininogenase	C + QM	24 wk	53.82 ± 5.42/54.06 ± 4.93	1, 2, 4, 7	3/5
Zhou and Femng[56], 2018	60/60	-	CT + Calcium Dobesilate	C + QM	12 wk	58.5 ± 6.7/57.9 ± 6.2	1, 2	-
Wang et al[57], 2019	48/52	-	CT + Calcium Dobesilate	C + QM	24 wk	66.8 ± 6.3/66.7 ± 6.2	1, 7	0/0
Wang[58], 2017	47/47	-	CT + Calcium Dobesilate	C + QM	12 wk	54.3 ± 4.9/54.5 ± 4.8	1, 4, 7	0/0
Yin[59], 2018	46/50	-	Calcium Dobesilate	C + QM	12 wk	55.27 ± 5.42/54.63 ± 5.28	1, 2, 7	0/0
Xin et al[60], 2019	38/38	-	Epalrestat	C + QM	12 wk	55.1 ± 3.3/55.5 ± 3.2	1, 3, 7	0/0
Zhang[61], 2017	39/39	-	Calcium Dobesilate	C + QM	12 wk	56.8 ± 2.5/56.9 ± 2.1	1, 2, 5, 6, 7	0/0
Yue[62], 2016	38/57	-	CT	C + QM	24 wk	49.82 ± 6.17/50.67 ± 5.23	1	-
Zheng et al[63], 2014	15/15	-	CT	C + QM	24 wk	50.4 ± 3.1/55.2 ± 4.7	1	-
Yang et al[64], 2013	36/35	-	CT	C + QM	24 wk	50.94 ± 8.01/50.23 ± 7.15	1	-
Huang[65], 2020	20/20	-	Calcium Dobesilate	C + DS	16 wk	52.16 ± 2.45/53.16 ± 2.26	1, 2, 3, 5, 6	-
Zheng and Ji[66], 2021	43/44	-	CT	C + DS	8 wk	57.52 ± 6.41/58.21 ± 6.35	1, 4	-
Meng et al[67], 2011	28/30	-	CT + Calcium Dobesilate	C + DS	24 wk	51.20 ± 7.90/50.60 ± 8.70	1, 7	0/0
Wang[68], 2004	16/28	-	CT + Calcium Dobesilate	C + DS	16 wk	50.5 ± 9.36/50.4 ± 8.70	1	-
Zhao[69], 2019	53/53	TRD	CT	C + DS	8 wk	57.5 ± 14.8/56.8 ± 13.4	1, 3, 4, 7	0/0
Ma et al[70], 2016	34/48	-	CT	C + DS	24 wk	59.16 ± 9.73/59.01 ± 10.58	5, 6, 7	0/0
Chen et al[71], 2007	25/25	-	CT	C + DS	8 wk	60.56/62.42	2, 3	-
Xu[72], 2019	43/43	TRD	Calcium Dobesilate	C + DS	16 wk	53.06 ± 4.39/53.11 ± 4.41	1, 3, 7	0/0
Huang et al[73], 2021	45/45	TRD	CT + Calcium Dobesilate	C + DS	24 wk	67.3 ± 5.1/67.5 ± 5.3	2, 4, 7	3/4
Jiao[74], 2018	75/75	-	CT + Calcium Dobesilate	C + DS	8 wk	56.31 ± 2.19/56.24 ± 3.86	1	-
Li[75], 2017	89/89	-	CT + Calcium Dobesilate	C + DS	8 wk	55.8 ± 6.8/56.5 ± 7.2	1, 5, 6	-
Yan and Yuan[76], 2014	20/60	-	CT	C + DS	24 wk	68.8/65.6	2, 3	-
Zhou[77], 2008	18/28	-	Calcium Dobesilate	C + DS	24 wk	50.50 ± 9.36/50.40 ± 8.70	1	-
Miao[78], 2020	24/34	TRD	Calcium Dobesilate	C + DS	16 wk	57.46 ± 4.41/57.33 ± 4.26	2, 3	-
Ruan et al[79], 2017	35/35	-	Calcium Dobesilate	C + DS	16 wk	52.8 ± 1.7/52.5 ± 1.1	1, 3, 5, 6, 7	0/0
Yin et al[80], 2013	50/50	-	CT + Calcium Dobesilate	C + DS	8 wk	59.7/57.9	1, 3	-
Zhu[81], 2018	57/57	-	CT	C + DS	12 wk	64.12 ± 1.36/64.17 ± 1.38	1, 2, 3	-
Yang et al[82], 2013	32/33	-	CT	C + DS	8 wk	54.2 ± 10.8/55.4 ± 12.1	5, 6	-
Bai[83], 2017	38/38	TRD	CT + Calcium Dobesilate	C + DS	16 wk	-	1, 2, 3, 4, 7	0/0
Guo[84], 2015	35/100	-	CT	C + DS	24 wk	59.6 ± 9.7/59.0 ± 10.6	5, 6	-
Liu[85], 2018	89/89	TRD	CT	C + DS	4 wk	54.97 ± 4.88/55.02 ± 5.01	5, 6	-
Liu[86], 2019	41/42	-	Pancreatic Kininogenase	C + HXMM	12 wk	-	3, 7	2/2
Zhao and Liu[87], 2021	30/30	-	CT + Calcium Dobesilate	C + HXMM	12 wk	64.84 ± 4.26/65.09 ± 4.37	1, 7	4/2
Gao et al[88], 2020	128/128	TRD	CT + Calcium Dobesilate	C + HXMM	12 wk	57.65 ± 7.82/58.14 ± 7.63	1, 3, 7	4/3
Li[89], 2021	34/34	Lottery	CT + Calcium Dobesilate	C + HXMM	12 wk	68.49 ± 4.62/67.84 ± 4.57	1, 3	-
Wang et al[90], 2018	100/100	-	Pancreatic Kininogenase	C + HXMM	12 wk	50.62 ± 6.91/50.96 ± 6.71	1, 3, 7	4/2
Zhang and Wang[91], 2018	39/39	-	CT	C + HXMM	12 wk	-	1, 2	-
Ye et al[92], 2019	88/88	TRD	Calcium Dobesilate	C + HXMM	12 wk	60.9 ± 13.4/60.5 ± 13.4	1, 5, 6	-
Yu[93], 2019	30/30	-	Epalrestat	C + HXMM	12 wk	-	1, 7	2/3
Du et al[94], 2015	26/25	TRD	CT	C + HXMM	12 wk	53.39 ± 4.96/52.13 ± 5.01	1, 7	0/0
Song[95], 2013	40/40	-	CT	C + QJDH	12 wk	-	1, 7	0/0
Li[96], 2019	40/40	-	Mecobalamin	C + QJDH	24 wk	61.25 ± 6.75/60.85 ± 6.57	1, 3, 4, 7	0/0
Li and Wei[97], 2019	54/54	-	CT + Calcium Dobesilate	C + QJDH	20 wk	56.1 ± 3.7/55.4 ± 3.1	1, 3, 4, 5, 6, 7	0/0
Wu[98], 2018	29/29	TRD	Pancreatic Kininogenase	C + QJDH	12 wk	52.4 ± 10.8/52.3 ± 9.2	1, 5, 7	0/0
Guan[99], 2017	40/40	-	CT + Calcium Dobesilate	C + QJDH	24 wk	40.0 ± 3.1/41.1 ± 2.0	1, 5, 6, 7	6/5
Ainu et al[100], 2019	50/50	-	CT + Calcium Dobesilate	C + QJDH	4 wk	53.02 ± 5.39/52.61 ± 5.39	2, 3, 4	-
Fu[101], 2019	40/40	-	Calcium Dobesilate	C + SDMM	24 wk	-	5, 7	7/2
Ji and Liu[102], 2022	52/52	Lottery	Calcium Dobesilate	C + SDMM	12 wk	56.53 ± 4.09/56.63 ± 4.02	1, 3, 4, 7	7/5
Jin and Zhang[103], 2019	71/71	-	CT + Calcium Dobesilate	C + SDMM	16 wk	62.39 ± 8.34/63.07 ± 8.08	1, 7	9/2
Liu et al[104], 2019	60/60	TRD	CT + Calcium Dobesilate	C + SDMM	16 wk	57.10 ± 9.26/57.54 ± 8.11	1, 3, 4, 7	0/0
Pang[105], 2015	40/40	-	CT	C + SDMM	16 wk	49.6 ± 5.3/49.4 ± 5.7	1	-
Deng et al[106], 2018	40/40	TRD	Calcium Dobesilate	C + DGBX	12 wk	59.48 ± 8.22/59.62 ± 8.30	1, 3, 7	0/0
Wang and Chen[107], 2020	75/75	-	Calcium Dobesilate	C + DGBX	12 wk	62.38 ± 2.00/62.40 ± 2.02	1, 4	-
Wu[108], 2013	33/34	-	CT	C + DGBX	12 wk	-	1, 2, 5, 6, 7	0/0
Sun et al[109], 2019	90/92	-	CT	C + DGBX	12 wk	55.3 ± 3.7/55.9 ± 3.5	1, 3, 7	10/6
Yu[110], 2020	28/28	-	CT + Calcium Dobesilate	C + DGBX	12 wk	60.01 ± 8.26/60.48 ± 8.11	1, 2	-
Xu[111], 2018	43/43	TRD	CT	C + DGBX	12 wk	56.2 ± 7.3/56.6 ± 7.1	1, 7	4/0
Huang[112], 2017	54/54	TRD	Iodized Lecithin	C + XFZY	8 wk	62.15 ± 11.80/61.84 ± 12.11	2	-
Zhu[113], 2010	36/36	TRD	CT	C + XFZY	8 wk	55.42 ± 5.35/55.73 ± 5.10	1, 5, 6, 7	0/0
Xiong and Chen[114], 2019	43/43	TRD	Calcium Dobesilate	C + XFZY	16 wk	53.14 ± 7.25/54.28 ± 7.13	2, 5, 6	-
Liu[115], 2020	57/57	Lottery	CT	C + XFZY	16 wk	50.38 ± 3.67/50.47 ± 3.22	2	-
Gong et al[116], 2014	40/40	-	CT	C + XFZY	12 wk	57.24 ± 10.60/55.36 ± 9.28	1, 5	-
Hao[117], 2012	84/66	-	CT	C + XFZY	4 wk	-	1	-
Huang[118], 2004	50/70	-	CT	C + XFZY	12 wk	64.5/65	1	-
Zhang[119], 2019	46/46	-	CT	C + BYHW	8 wk	64.37 ± 9.13/66.46 ± 9.90	1	-
Yang[120], 2019	40/40	TRD	CT + Calcium Dobesilate	C + BYHW	8 wk	48.66 ± 8.82/50.35 ± 9.06	1, 2, 5	-
Tian[121], 2019	27/27	-	Metformin	C + BYHW	12 wk	53.05 ± 1.18/53.12 ± 1.12	1	-
Qu and Yao[122], 2009	30/32	-	CT + Iodized Lecithin	C + BYHW	12 wk	-	1	-

A total of 6 studies[95-100] used Qiju Dihuang Pills (QJDH) (consisting of Lycii Fructus/Gouqizi in chinese; Rehmanniae Radix Praeparata/Dihuang in chinese; Chrysanthemi Flos/Juhua in chinese; Cornus Officinalis Sieb. Et Zucc./Shanzhuyu in chinese; Rhizoma Dioscoreae/Shanyao in chinese; Poria Cocos(Schw.) Wolf./Fuling in chinese; Alisma Orientale (Sam.) Juz./Zexie in chinese; Cortex Moutan/Mudanpi in chinese). Four[95-97,100] of these six studies added Paeoniae Radix Alba (Baishao in Chinese), Tribulifructus (Jili in Chinese), Cassiae Semen (Juemingzi in Chinese), and Angelicae Sinensis Radix (Danggui in Chinese). Although there are some changes in components, the whole is still dominated by QJDH, which has the same efficacy as QJDH, so in this study, we classified these 6 studies as using QJDH. The composition of all Oral Chinese medicine (OCM) in this study is shown in Supplementary Table 2, and the source of OCMs, quality control report and chemical analysis report are shown in Supplementary Table 3. TRD: Table of random digit; CT: Conventional treatment, including blood glucose control, blood pressure lowering, lipid regulation and other conventional treatments; E: Experimental group; C: Control group; QM: Qiming Granules; DS: Compound Danshen Dripping Pills; XFZY: Xuefu Zhuyu Decoction; DGBX: Danggui Buxue Decoction; HXMM: Hexue Mingmu Tablets; SDMM: Shuangdan Mingmu Capsules; BYHW: Buyang Huanwu Decoction; QJDH: Qiju Dihuang Pills; XST: Compound Xueshuantong Capsule; -: Not mentioned; 1: Total effective rate; 2: Visual acuity; 3: Fundus hemorrhage area; 4: Vascular endothelial growth factor; 5: Fasting blood glucose; 6: Glycated hemoglobin; 7: Adverse reactions.

Table 2 Occurrence of adverse reactions of Oral Chinese medicine

OCMs compound	Group	Sample	Hypoglycemia	Stomach upset (n)	Loss of appetite	Insomnia	Fever	Dizzy	Nausea	Liver damage	Kidney damage	Macular edema	Corneal damage	Itchy skin	Fatigue
Xueshuantong Capsules	C	42	0	14	5	0	0	0	6	8	9	0	0	0	0
	E	28	0	8	8	0	0	0	8	2	2	0	0	0	0
Qiming Granules	C	23	0	1	0	0	0	0	0	3	2	8	7	1	1
	E	12	0	2	0	0	0	0	0	1	0	3	3	1	2
Compound Danshen Dripping Pills	C	3	0	3	0	0	0	0	0	0	0	0	0	0	0
	E	4	0	4	0	0	0	0	0	0	0	0	0	0	0
Hexue Mingmu Tablets	C	16	2	4	3	0	0	0	3	0	0	0	0	3	1
	E	12	0	6	2	0	0	0	1	0	0	0	0	2	1
Qiju Dihuang Pills	C	6	0	0	0	0	0	0	6	0	0	0	0	0	0
	E	5	0	0	0	0	0	0	5	0	0	0	0	0	0
Shuangdan Mingmu Capsules	C	23	0	5	0	0	5	2	8	0	0	0	0	0	3
	E	9	0	2	0	0	2	2	3	0	0	0	0	0	0
Danggui Buxue Decoction	C	14	2	4	0	2	0	4	0	0	0	0	2	0	0
	E	6	2	2	0	0	0	0	1	0	0	0	0	0	1

OCM: Oral Chinese medicine; E: Experimental group; C: Control group; The numbers in the table represent the number of patient cases.