Treatment of Diabetic Retinopathy with Blood Stasis， Collateral Obstruction， and Qi and Yin Deficiency Syndrome with Tongluo Mingmu Capsules： A Randomized， Double-blind， and Multi-center Phase Ⅲ Clinical Trial / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ2=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ2=17.927， P<0.01）. The disappearance rate of dry eyes （χ2=8.305）， dull complexion （χ2=4.053）， lassitude （χ2=10.267）， shortness of breath （χ2=8.494）， and dry stool （χ2=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ2=8.382）， fundus changes （χ2=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

The effect of intravitreal ranibizumab on the expression of cytokines in aqueous humor of patients with macular edema due to branch retinal vein occlusion / 中华眼底病杂志

Objective:To study the changes the changes of cytokine expression the aqueous humor of patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME) before and after intravitreal ranibizumab (IVR).Methods:A prospective clinical study. From June 2018 to June 2021, 31 eyes of 31 patients with non-ischemic BRVO-ME diagnosed by ophthalmic examination in Department of Ophthalmology, Beijing Hepingli Hospital were included in the study. Among them, 15 males had 15 eyes, and 16 females had 16 eyes. Age was 70 (65, 72) years; the course of disease was 10 (9, 15) days. All of them were first-time patients. All eyes were treated with IVR once a month for 3 consecutive months. At the end of each IVR treatment, 0.1 ml aqueous humor was extracted immediately. The concentrations of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aqueous humor were detected by flow cytometry. The concentrations of cytokines in aqueous humor before and after treatment were compared by Kruskal-Wallis or Wilcoxon signed-rank test. Spearman correlation analysis was performed on the correlation between VEGF and MCP-1 expression level in aqueous humor before treatment.Results:The concentrations of VEGF and ICAM-1 in aqueous humor were significantly lower at 1 month after treatment compared with that before treatment, and at 2 months after treatment compared with that at 1 month after treatment ( Z=4.03, 3.25, 2.50, 3.48; P<0.05); the concentrations of IL-6 and VCAM-1 increased and the concentration of MCP-1 decreased, but there was no significant difference ( Z=-0.21, 1.42, 0.86, -0.53, 0.92, -1.57; P>0.05). Spearman correlation analysis showed that there was a strong positive correlation between VEGF and MCP-1 in aqueous humor before treatment ( r=0.78, P<0.001). Conclusion:The concentrations of VEGF and ICAM-1 in aqueous humor significantly decrease after IVR treatment in BRVO-ME; the concentrations of IL-6, MCP-1 and VCAM-1 do not obviously change.

The effect of intravitreal ranibizumab on the expression of cytokines in aqueous humor of patients with macular edema due to branch retinal vein occlusion / 中华眼底病杂志

Objective:To study the changes the changes of cytokine expression the aqueous humor of patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME) before and after intravitreal ranibizumab (IVR).Methods:A prospective clinical study. From June 2018 to June 2021, 31 eyes of 31 patients with non-ischemic BRVO-ME diagnosed by ophthalmic examination in Department of Ophthalmology, Beijing Hepingli Hospital were included in the study. Among them, 15 males had 15 eyes, and 16 females had 16 eyes. Age was 70 (65, 72) years; the course of disease was 10 (9, 15) days. All of them were first-time patients. All eyes were treated with IVR once a month for 3 consecutive months. At the end of each IVR treatment, 0.1 ml aqueous humor was extracted immediately. The concentrations of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aqueous humor were detected by flow cytometry. The concentrations of cytokines in aqueous humor before and after treatment were compared by Kruskal-Wallis or Wilcoxon signed-rank test. Spearman correlation analysis was performed on the correlation between VEGF and MCP-1 expression level in aqueous humor before treatment.Results:The concentrations of VEGF and ICAM-1 in aqueous humor were significantly lower at 1 month after treatment compared with that before treatment, and at 2 months after treatment compared with that at 1 month after treatment ( Z=4.03, 3.25, 2.50, 3.48; P<0.05); the concentrations of IL-6 and VCAM-1 increased and the concentration of MCP-1 decreased, but there was no significant difference ( Z=-0.21, 1.42, 0.86, -0.53, 0.92, -1.57; P>0.05). Spearman correlation analysis showed that there was a strong positive correlation between VEGF and MCP-1 in aqueous humor before treatment ( r=0.78, P<0.001). Conclusion:The concentrations of VEGF and ICAM-1 in aqueous humor significantly decrease after IVR treatment in BRVO-ME; the concentrations of IL-6, MCP-1 and VCAM-1 do not obviously change.

Efficacy and safety of compound anisodine injection for anterior ischemic optic neuropathy: a meta-analysis / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of compound anisodine (CA) injection for anterior ischemic optic neuropathy (AION).Methods:Studies, which were randomized controlled trials (RCT) of CA with routine treatment for AION from PubMed, The Cochrane Library, Web of Science, CNKI, Wanfang database, Chinese science and technology journals full-text database and CD-ROM database of Chinese Biology Medical disc published from January 1978 to June 2021 were searched.Included studies were screened by two researchers independently based on inclusion and exclusion criteria.After data collection and quality assessment, a meta-analysis of included studies was performed with Revman 5.3 software.Results:Thirteen RCT were included, involving 1 636 eyes, with 829 eyes in treatment group and 807 eyes in control group without CA treatment.It was found that the total effective rate of treatment group was higher than that of control group ( OR=3.25, 95% CI: 2.47-4.28, P<0.01), and the best corrected visual acuity of AION patients after CA treatment was significantly better than that of control group when articles with high heterogeneity were excluded (MD=0.14, 95% CI: 0.11-0.17, P<0.01) or not (MD=0.14, 95% CI: 0.12-0.16, P<0.01).The mean defect of visual field was significantly smaller and the mean sensitivity of visual field was higher in treatment group than control group (MD=-2.58, 95% CI: -3.98--1.19, P<0.01; MD=3.49, 95% CI: 3.07-3.91, P<0.01). Conclusions:CA shows good efficacy in the treatment of AION.It can improve visual acuity and mean sensitivity of visual field, decrease mean defect of visual field.

Characteristics and prognosis of visual field of G11778A mutation Leber hereditary optic neuropathy / 中华眼底病杂志

Objective:To analyze the characteristics and prognosis of visual field of Leber hereditary optic neuropathy (LHON) with G11778A mutation.Methods:A retrospective clinical study. Twenty-two (44 eyes) of LHON patients diagnosed with G11778A site mutation by mt-DNA examination from May 2008 to February 2018 in Ophthalmology Department of Dongfang Hospital of Beijing University of Chinese Medicine, were enrolled in this study. All patients underwent best corrected visual acuity (BCVA), visual field and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The thickness of the retinal nerve fiber layer (RNFL) in the 200μm×200μm annular region 1.73 mm outside the optic disc was measured by OCT. At least 7 visual field examinations were performed within one month before and after 2, 4, 8, 12, 18, 24 and 30 months of the course of disease by using Octopus 101 perimetry. Among 44 eyes, 27 eyes were detected with G2 procedure (G2 group) and 17 eyes were detected with LVC procedure (LVC group). The mean field defect (MD) and mean optical sensitivity (MS) were used as the main outcome indexes. According to the onset age, the patients were further divided into the ≤14 years old group and>14 years old group. There was a significant difference in initial logMAR BCVA between the G2 group and LVC group ( t=4.994, P=0.000), but there was no significant difference in gender ( χ2=1.896, P=0.169) and age ( t=0.337, P=0.708) between the two groups. Independent sample t test was used for comparison between groups, paired t test was used for comparison within groups, and one-way analysis of variance was used for comparison between groups. The statistical data were compared by χ2 test. Results:In the G2 group, the MD value of the subgroup of children (≤14 years old) decreased gradually during the follow-up period, and the MD value since 18 months after onset was significantly lower than the value of 2 months after onset ( t=3.813, 4.590, 5.033; P=0.002, 0.001, 0.000). No obvious visual field index changes were seen in other subgroups ( P>0.05). The central scotoma was the most common type of visual field defect in the early stage, and the diffuse defect was the most common type of visual field defect in the late stage. There was a significant difference in the types of visual field distribution between the early and late stage in G2 group ( χ2=17.414, P=0.015). There was no significant difference in the type of visual field distribution between the early and late stage in LVC group ( χ2=4.541, P=0.474). The MD value in the G2 group remained stable within 8 months after onset, but significantly improved after 18 months after onset ( t=2.100, 3.217, 3.566; P=0.046, 0.003, 0.001). The MS in the LVC group did not significantly improve during follow-up ( P>0.05). The average visual acuity of the G2 group was significantly improved from 12 months ( t=3.039, 3.678, 4.264, 5.078; P=0.008, 0.002, 0.001, 0.000). The visual acuity of the eyes in the G2 group was better than that of the LVC group during all follow-up periods ( P≤0.05). The RNFL thickness of all patients continued to decrease after onset, but the RNFL thickness was significantly higher at 4, 8, 18, 24, 30 months in the G2 group than those in the LVC group ( t=2.471, 2.269, 2.474, 2.509, 2.782; P=0.018, 0.028, 0.017, 0.016, 0.008). Conclusions:The main types of visual field defect of LHON with G11778A mutation are the central scotoma in the early stage, while the diffuse defect and central scotoma are both very common in the later stage. The visual field of LHON patients examined by G2 procedure is significantly improved during the follow-up, as well as the visual acuity improved significantly, and the visual field improvement in younger cases (≤14 years old) is better than that of older cases (>14 years old), but the visual field of the LVC procedure cases did not improve during follow-up.

A novel mutation T8821G in mitochondrial DNA may be associated with Leber's hereditary optic neuropathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.</p><p><b>METHODS</b>Ophthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.</p><p><b>RESULTS</b>The ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment.</p><p><b>CONCLUSION</b>Above observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.</p>

Compound anisodine use as a role in traumatic optic neuropathies treatment: a meta-analysis / 中华眼底病杂志

Objective To estimate the quality and efficacy of the academic thesis of compound anisodine in traumatic optic neuropathies(TON)treatment. Method We searched Chinese database last or"blunt trauma"as key words,and analyzed them using the standard of evidence-based medicine(EBM).Result 6 RCTS with a total of 415 eyes included are retrieved,and the OR value is 6.54 with a 95%CI of[4.14,10.35],P＜0.00001,the difference is significant;sub-category analyses are made and both show significant difference(P＜0.0001). Conclusion The existing evidence supports that prognosis of TON is better when compound anisodine are adopt in treatment,and this effect is significant in steroid treatment.Compound anisodine can be used alone for TON treatment.However.because there are only 6 thesis are retrieved and all of them have methodological short-comings,the evidence is not convincing.There is an urgent need of well-planed,large-scale and multiple-center studies to assess the role of compound anisodine in traumatic optic neuropathies treatment.

Differentiation of Wei,Qi,Ying and Xue on Acute Contagious Conjunctivitis / 浙江中医药大学学报

[Objective] To explore the differentiation of Wei Qi Ying Xue on febrile disease,its treatment on external oculopathy of acute contagious conjunctivitis,which is failed in western medicine.[Method] Under the characteristics of the disease and the theory of differentiation of Wei Qi Ying Xue,its location is in Wei system,it should dispel with pungent and cool drugs to remove lung hotness,by applying revised normal pungent and cool prescription Yinqiao San;for disease in both Wei and Qi,it should use revised Yinqiao San and Baihu Tang to relieve exterior syndrome and clear hot toxin by pungent and cool drugs;if the location is in Qi system,it should take revised Baihu Tang and Dachengqi Tang to clear away heat and toxic material or by purgation;if it happens both in Qi and Ying(blood),take Qingying Tang and Xijiao Dihuang Tang to clear away heat and toxic material,cool and dispel blood;when the heat is removed and the fluid is injured,the bad heat is pondering,it should take Shashen Maidong Tang to clear away the remaining heat and produce fluid.[Result] It gets good result with correct differentiation.[Conclusion] As long as you have correct differentiation of signs,can the febrile disease theory in national medicine be applied in the treatment of external oculopathy flexibly.

The major types and clinical manifestations of mitochondrial DNA mutations in Chinese patients with Leber's hereditary optic neuropathy / 中华眼底病杂志

Objective To investigate the major types and clinical manifestations of mitochondrial DNA (mtDNA)mutations in Chinese patients with Leber′s hereditary optic neuropathy(LHON). Methods A total of 119 patients with bilateral optic neuropathy from 117 pedigrees, including 37 with determinate diagnosis of LHON(group A) and 82 with suspected LHON(group B),were tested for mtDNA mutations by using single-strand conformational polymorphism, mutation-specific primer polymerase chain reaction and sequencing. Pertinent clinical data and history of the patients with the 11778 mutation were collected. Results Nucleotide positions(np)11778 mutation and np 14484 mutation was found in 33 (89.2%) and 3 (8.1%) patients respectively in group A, while np 11778 mutation was obtained in 26 (31.7%)in group B. No 3460 mutation was found in group A or B. The clinical manifestations of 59 patients with np 11778 mutation were as follows: acute or chronic visual loss,no ophthalmalgia, the age of onset of 10-25, and either a central or paracentral scotoma in perimetry. The visual recovery rate was 8.6%～11.6%. Conclusion Chinese patients with LHON have a very high incidence of np 11778 mutation and the clinical manifestations of the patients with np 11778 mutation are similar to those of Caucasian patients.