白内障超声乳化吸除术对糖尿病视网膜病变进展影响的Meta分析

目的 采用Meta分析的方法系统评价白内障超声乳化吸除术对糖尿病合并白内障患者术后糖尿病视网膜病变进展及糖尿病性黄斑水肿发生率的影响。设计 系统综述。研究对象 Medline、EMbase、Cochrone图书馆及中国生物医学文献数据库和中国期刊全文数据库中一眼行白内障超声乳化术,对侧未手术眼作为对照的糖尿病合并白内障患者为研究对象的文献。方法 对纳入文献进行Meta分析。计算机检索上述数据库,同时手工检索相关书籍、期刊和会议论文及其参考文献。依据纳入和排除标准筛选文献,对纳入研究进行数据提取。统计学分析采用RevMan5.0软件,二分类变量采用比值比（OR）及其95%置信区间CI来表示。主要指标 白内障超声乳化吸除术后双眼糖尿病视网膜病变的进展率及糖尿病性黄斑水肿的发生率。结果  7项研究纳入分析,其中手术眼579眼,对侧未手术眼574眼作为对照。手术眼术后糖尿病视网膜病变进展率高于对侧未手术眼（OR=1.47,95%CI：1.09～1.98,P=0.01）。手术眼术后糖尿病性黄斑水肿发生率高于对侧未手术眼（OR=1.89,95%CI：1.05～3.39,P=0.03）。结论  白内障超声乳化吸除术会加速糖尿病合并白内障患者糖尿病视网膜病变进程且增加糖尿病性黄斑水肿的发生率,但仍需大样本、长期随访的研究进一步证实。     

候选基因多态性与糖尿病视网膜病变相关性的Meta分析

目的 候选基因多态性位点与2型糖尿病患者（type 2 diabetes mellitus，T2DM）的糖尿病视网膜病变（diabetes retinopathy，DR）相关性的Meta分析。设计 Meta分析。研究对象  T2DM的DR候选基因多态性的英文或中文文献。方法 在Pubmed（National Center for Biotechnology Information）、ISI（Web of Kowledge）、Embase和中国知网（China National Knowledge Internet，CNKI）4个数据库中，系统性检索、收集2019年1月1日以前以中文和英文发表的关于色素上皮源性因子（pigment epithelium derived factor，PEDF）、肿瘤坏死因子（tumor necrosis factor-α，TNF-α）和对氧磷酶-1（paraoxonase 1，PON1）三个基因的多态性位点与DR相关性的文献。采用Stata 12.0软件计算合并优势比（pooled odds ratio，pooled OR），分析组间异质性（Pheterogeneity）和发表偏倚（publication bias）。主要指标 OR值、组间异质性，发表偏倚。结果 共13篇研究纳入本Meta分析，包括2729例DR和3420例糖尿病对照。PEDF基因的 rs12948385位点（显性模型：OR=1.371，95%CI：1.072~1.755，P=0.012；等位基因模型：OR=1.266，95%CI：1.028~1.560，P=0.027）和PON1基因的L55M位点（隐性模型：OR=2.998，95%CI：1.282~7.010，P=0.011）与DR相关；TNF-α基因的rs1800629位点与PDR相关（等位基因模型：OR=1.291，95%CI：1.019~1.636，P=0.034）。结论  PEDF基因的 rs12948385位点、PON1基因的L55M位点可能与DR相关；TNF-α基因的rs1800629位点可能与PDR相关。     

Efficacy and safety of vitrectomy with internal limiting membrane peeling for diabetic macular edema: a Meta-analysis

AIM: To evaluate the efficacy and safety of vitrectomy with internal limiting membrane (ILM) peeling for diabetic macular edema (DME). METHODS: The PubMed, Embase, Web of Science, Cochrane, SionMed, ClinicalTrials.gov, CNKI databases and Wanfang databases, published until Oct. 2017, were searched to identify studies comparing the clinical outcomes following vitrectomy with and without ILM peeling, for treating DME. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for vitrectomy with and without ILM peeling with regard to best corrected visual acuity (BCVA), central macular thickness (CMT), and complication incidents. RESULTS: A total of 14 studies involving 857 eyes were included of which three studies were Chinese and the rests were English literatures. Meta-analysis indicated that compared with vitrectomy alone, vitrectomy with ILM peeling could improve BCVA more obviously (OR=1.66, 95%CI: 1.12-2.46, P=0.01) and had higher rate of CMT reduction (OR=3.89, 95%CI: 1.37-11.11, P=0.01). There were significant statistical differences between the two surgical methods for both BCVA and CMT (P<0.05). For the incidence of intraoperative and postoperative complications, the incidence of epiretinal membrane (ERM) was slightly lower in the ILM peeling group than the group without ILM peeling (OR=0.38, 95%CI: 0.07-2.00, P=0.25), although insigni?cant statistically. Other incidences of overall complications, iatrogenic peripheral retinal break and increased intraocular pressure indicated no significant difference between two groups (OR=1.19, 95%CI: 0.82-1.73, P=0.36; OR=1.21, 95%CI: 0.66-2.21, P=0.53; OR=1.34, 95%CI: 0.75-2.40, P=0.32). CONCLUSION: Vitrectomy is effective for DME and the effect can be improved by additional ILM peeling, especially for anatomical efficacy, without increasing the incidence of intraoperative and postoperative complications. However, it is imperative to gain more evaluation in the future due to the paucity of prospective randomized study.     

Effectiveness of peripheral defocus spectacle lenses in myopia control: a Meta-analysis and systematic review

AIM: To evaluate the effectiveness of peripheral defocus spectacle lenses (PDLs) in myopia control. METHODS: Literature retrieval on PubMed, Cochrane Library, Embase, and Web of Science databases, and the search time limit was from the establishment of each database to December 29, 2021 were conducted. Change of spherical equivalent refraction (SER) and axial change (AL) were extracted from the literatures that met the inclusion criteria, and RevMan5.3 software was used for Meta-analysis. RESULTS: A total of 4 randomized controlled trials (RCTs) were included in this Meta-analysis, involving 770 myopic children. The results showed that PDLs could delay the progression of myopia in children with myopia compared with single vision spectacle lenses (SVLs; WMD=0.21 D, 95%CI: 0.01, 0.41, P=0.04). However, there was no significant difference in controlling the growth of axial length (AL) in myopic children (WMD=-0.10 mm, 95%CI: -0.21, 0.01, P=0.07). The results of the effectiveness of myopia control between the two spectacle lenses showed that PDLs were more effective in controlling the progression of myopia (OR=5.73, 95%CI: 2.58, 12.70, P<0.001) and delaying the growth of AL (OR=44.25, 95%CI: 8.84, 221.58, P<0.001) than SVLs, and the differences were statistically significant. CONCLUSION: PDLs can control the progression of myopia compared with SVLs, but cannot delay the growth of AL, and the effectiveness of PDLs in myopia control better than SVLs.     

Comparison of conbercept and ranibizumab for the treatment efficacy of diabetic macular edema: a Meta-analysis and systematic review

AIM: To evaluate the efficacy of intravitreal injection of conbercept (IVC) and ranibizumab (IVR) in patients with diabetic macular edema. METHODS: Reviewers have searched 12 databases, including PubMed, Medline, EMBASE, Web of Science, Springer, ScienceDirect, OVID, Cochrane Library, ClinicalTrials.gov, cqVIP, WanFangdata and China National Knowledge Infrastructure (CNKI), up to December 28, 2018. RevMan 5.3 (Cochrane Library Software, Oxford, UK) was employed for statistical analysis. Fixed and random effects models were applied to assess heterogeneity. Odds ratio (OR) was applied for dichotomous variables; weighted mean difference (WMD) was applied for continuous variables. The confidence interval (CI) was set at 95%. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were employed to analyze the improvement of DME patients. Inclusion criteria for picking out studies were retrospective studies and randomized controlled trials (RCTs) that compared IVC and IVR for the treatment of diabetic macular edema. RESULTS: Four retrospective studies and five RCTs were included with a total of 609 patients. No statistically significant difference was observed in mean CMT and mean BCVA in the baseline parameters [BCVA (WMD: -0.48; 95%CI: -1.06 to 0.10; P=0.1), CMT (WMD: -0.83; 95%CI: -15.15 to 13.49; P=0.91). No significant difference was found in the improvement of BCVA and adverse event (AE) in IVC group, compared with IVR group after treatment of loading dosage [the 1st month BCVA (WMD: 0.01; 95%CI: -0.26 to 0.27; P=0.96), the 3rd month BCVA (WMD: -0.04; 95%CI: -0.14 to 0.06; P=0.46); the 6th month BCVA (WMD: -0.24; 95%CI: -1.62 to 1.14; P=0.73)], AE (OR: 0.84; 95%CI: 0.38 to 1.84; P=0.66)]. A slight difference was found in the effectiveness rate (OR: 1.70; 95%CI: 0.97 to 2.96; P=0.06), There were statistically significant differences between IVC and IVR treatment in terms of CMT [1st month CMT (WMD: -19.88; 95%CI: -27.94 to -11.82; P<0.001), 3rd month CMT (WMD: -23.31; 95%CI: -43.30 to -3.33; P=0.02), 6th month CMT (WMD: -74.74; 95%CI: -106.22 to -43.26; P<0.001)]. CONCLUSION: Pooled evidence suggests that both IVC and IVR are effective in the therapy of diabetic macular edema and affirms that IVC presents superiority over IVR therapy in regard of CMT in patients with diabetic macular edema, but no statistically significant difference with regard to visual improvement. Relevant RCTs with longer-term follow-up are necessary to back up our conclusion.     

抗血管内皮生长因子治疗糖尿病黄斑水肿患者短期疗效影响因素分析

目的　观察抗血管内皮生长因子（VEGF）玻璃体内注射治疗糖尿病黄斑水肿（DME）患者短期疗效的影响因素。方法　回顾性分析。纳入接受玻璃体内注射抗VEGF药物的DME患者67例67眼,采集患者一般信息、全身病史及相关血液学检测指标（血糖、血常规、血脂、生化、肾功能等）、眼部病史及眼科相关检查结果［视力、眼压、眼底彩色照相、OCT相关影像学指标、荧光素眼底血管造影（FFA）等］。采用单因素及二元logistic回归分析进行数据统计。结果　将单因素分析结果中有统计学差异的指标纳入二元logistic回归分析,结果显示,基线1 mm黄斑中心视网膜体积小（OR=0.001,95%CI为0.001~0.036）、1 mm 黄斑中心视网膜厚度薄（OR=0.994,95%CI 为0.988~1.000）、白细胞计数低（OR=0.561,95%CI为0.332~0.948）、血红蛋白浓度高（OR=1.076,95%CI为1.021~1.135）、红细胞计数高（OR=11.798,95%CI为 1.854~75.078）、视力下降时间长（OR=2.008,95%CI为 1.053~3.830）、基线最佳矫正视力低（OR=0.274,95%CI为 0.093~0.804）是DME患者抗VEGF治疗后短期疗效不佳的独立影响因素。结论　DME患者基线时视功能与眼部解剖结构以及全身情况可能影响抗VEGF治疗的短期疗效。     

Atropine 0.01% eye drops slow myopia progression: a systematic review and Meta-analysis

AIM: To evaluate the effects of atropine 0.01% on slowing myopia progression. METHODS: We searched for relevant studies in the Cochrane Library, PubMed, Embase, Ovid, CBM, CNKI, VIP and Wan Fang Data in Chinese. A supplementary search was conducted in OpenGrey (System for Information on Grey Literature in Europe), the ISRCTN registry, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from the dates of inception to June 30, 2018. RESULTS: Seven randomized controlled trials (RCTs) with a total of 1079 subjects were included (505 in the atropine 0.01% group and 574 in the control group). The results showed that the atropine 0.01% group exhibited significantly greater control of axial growth than the control group [MD=-0.12, 95%CI (-0.19, -0.06)]. There was also a statistically significant difference between the atropine 0.01% and control groups in the changes in axial length [MD=-0.14, 95%CI (-0.25, -0.03)], but the quality of evidence was low. There were no significant differences between the atropine 0.01% and control groups in the overall effect with respect to diopter value, change in diopter, distance vision and intraocular pressure [MD=0.08, 95%CI (-0.27, 0.42); MD=0.09, 95%CI (-0.17, 0.36); MD= -0.01, 95%CI (-0.02, 0.00); MD=0.08, 95%CI (-0.56,0.40)]. The sensitivity analysis showed that the conclusion of the Meta-analysis is relatively stable. With respect to adverse events, there were significant differences between the atropine 0.01% and control groups [OR=0.26, 95%CI (0.11, 0.61)]. CONCLUSION: Based on the available evidence, atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.     

上海市新泾社区2型糖尿病患者5年随访的前瞻性调查研究3.糖尿病视网膜病变和糖尿病黄斑水肿的好转及促进因素

背景 对2型糖尿病患者的长期随访过程中发现,部分糖尿病视网膜病变(DR)和糖尿病黄斑水肿(DME)患者未经眼底激光光凝、内眼手术或眼内药物治疗眼底病变可好转,但其影响因素尚不清楚.目的 探讨中国2型糖尿病患者DR和DME自行好转的发生率及促好转影响因素. 方法 采用前瞻性观察研究方法,于2007-2012年对上海市新泾社区中符合纳入标准的778例2型糖尿病患者进行连续5年的流行病学调查和随访,收集患者一般资料,对患者行全身体格检查、实验室血生化指标检查、眼部检查和眼底照相,眼底照片读片采用盲法.采用国际临床分类方法和视网膜玻璃体增生情况将DR分为无明显DR和轻、中、重度非增生性DR及增生性DR;并将DME分为无、轻度、中度和重度DME.将DR好转和DME好转作为2个结局变量,好转为仅接受全身用药者至少一眼终末DR或DME分级较基线时下降至少1级且对侧眼DR无进展.采用Logistic多元回归分析判断年龄、性别、受教育程度、糖尿病发病年龄、糖尿病病程、肥胖及血肌酐、三酰甘油、总胆固醇和糖化血红蛋白(HbA1c)水平对结局变量的影响.结果 2007年基线调查时发现DR患者456例,其中139例患者5年后至少1眼DR好转,好转率为30.48％.基线检查低HbA1c水平和低血肌酐水平是DR好转的促进因素[HbA1c:优势比(OR)=0.53,95％可信区间(CI)]:0.45 ～0.63,P＜0.01;血肌酐:OR=0.98,95％ CI:0.97 ～0.99,P＜0.01).基线调查时发现DME 158例,其中20例5年后至少1眼好转,好转率为12.66％.高基线血糖水平是DME好转的唯一、独立影响因素(OR=1.47,95％ CI:1.14～1.91,P＜0.01).结论 降低2型糖尿病DR患者的血糖和血肌酐水平有助于DR好转,快速降低血糖水平有助于DME的好转.     

MnSOD Val16Ala polymorphism associated with retinopathy risk in diabetes: a PRISMA-compliant Meta-analysis of case-control studies

AIM: To investigate the association of Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism with diabetic retinopathy (DR). METHODS: PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Subgroup, sensitivity, and cumulative analyses were performed. Publication bias was also analyzed. RESULTS: Eight studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48-0.91, P<0.0001), this result was demonstrated to be relatively stable in cumulative analysis. No significant publication bias was found. This polymorphism was also associated with the risk of DR in Caucasians under the dominant model (OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model (OR=0.31, 95%CI=0.11-0.88, P=0.03). CONCLUSION: These findings suggest that the MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention should be paid to carriers of these susceptibility genes.     

All-trans retinoic acid increases ARPE-19 cell apoptosis via activation of reactive oxygen species and endoplasmic reticulum stress pathways

AIM: To explore the apoptosis of ARPE-19 cells after the treatment with different doses of all-trans-retinoic acid (ATRA). METHODS: ARPE-19 cells were used in the in-vitro experiment. Flow cytometry assay was employed to evaluate the level of reactive oxygen species (ROS) and apoptosis. The effects of ATRA (concentrations from 2.5 to 20 μmol/L) on the expression of endoplasmic reticulum stress (ERS) markers in vitro were evaluated by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR) assays. The contribution of ROS and ERS-induced apoptosis in vitro was determined by using N-acetyl-L-cysteine (NAC) and Salubrinal, an antagonist of NAC and ERS, respectively. RESULTS: Flow cytometry showed that ATRA significantly increased ARPE-19 cell apoptosis and ROS levels in each group (F=86.39, P<0.001; F=116.839, P<0.001). Western blot and qRT-PCR revealed that levels of CHOP and BIP were elevated in a concentration-dependent pattern after the cells were incubated with ATRA (2.5-20 μmol/L). The upregulation of VEGF-A and CHOP induced by ATRA could be inhibited by NAC (antioxidant) and Salubrinal (ERS inhibitor) in vitro. CONCLUSION: ATRA induces the apoptosis of ARPE-19 cells via activated ROS and ERS signaling pathways.     

社区2型糖尿病患者自我管理行为与糖尿病视网膜病变的相关分析

目的 了解社区2型糖尿病（T2DM）患者自我管理行为与糖尿病视网膜病变（DR）的关系。设计 横断面研究。研究对象 2015年7月在深圳市银湖社康中心进行年度体检的T2DM患者252例。方法 采用糖尿病患者自我管理行为量表进行问卷调查,根据结果将患者分为自我管理行为良好、中等、不良。同时测定空腹血糖（FBG）、糖化血红蛋白（HbA1c）。根据眼底检查分为无糖尿病视网膜病变（DWR）、非增生性糖尿病视网膜病变（NPDR）和增生性糖尿病视网膜病变（PDR）,比较DR患者与DWR患者的自我管理行为以及血糖指标控制情况。主要指标 糖尿病自我管理行为、FBG、HbA1c水平。结果 252例T2DM患者中228例（90%）完成调查,其中DR者62例（27.2%）,病程10年以上DR患者34例（54.8%）,明显多于DWR患者（65例,39.2%）（χ2=4.519,P=0.034）。228例T2DM患者自我管理行为良好率20.6%、中等50.9%、不良28.5%;其中,DR患者自我管理行为良好率11.3%低于DWR患者 （24.1%）（χ2=4.524,P=0.033）。228例T2DM患者血糖控制达标率FBG 29.4%、HbA1c 28.5%;其中DR患者血糖控制达标率FBG 19.4%、HbA1c 17.7%,低于DWR患者FBG 33.1%、HbA1c 32.5%（χ2=4.129,P=0.042;χ2=4.844,P=0.028）。病程为<5年、5~10年、>10年的T2DM患者自我管理行为不良率分别为15.0%、20.2%、41.4%（χ2=16.764,P=0.002）。分级为DWR、NPDR、PDR的T2DM患者自我管理行为不良率分别为25.9%、28.0%、66.7%（χ2=9.132,P=0.010）。多因素Logistic回归分析模型中,饮食行为（OR=0.241,95%CI:0.163~0.287）、运动行为（OR=0.536,95%CI:0.481~0.692）、遵医嘱用药（OR=0.056,95%CI:0.018~0.172）,FBG达标率（OR= 2.255,95%CI:1.315~3.873）、HbA1c达标率（OR=1.376,95%CI:1.197~1.584）以及糖尿病病程（OR=0.573,95%CI:0.038~0.714）与DR的发生及严重程度相关。结论 糖尿病病程长、饮食控制不佳、较少运动、用药欠规范和FBG、HbA1c控制不达标与DR的发病相关,提高社区T2DM患者自我管理行为有助于血糖控制,降低DR发生的风险。（眼科,2016, 25： 326－329）     

Sub-threshold micro-pulse diode laser treatment in diabetic macular edema: A Meta-analysis of randomized controlled trials

AIM: To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation (SDM) and traditional modified Early Treatment Diabetic Retinopathy Study (mETDRS) treatment protocol in diabetic macular edema (DME). METHODS: A comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for DME. The participants were type I or type II diabetes mellitus with clinically significant macular edema treated by SDM from previously reported randomized controlled trials (RCTs). The primary outcome measures were the changes in the best corrected visual acuity (BCVA) and the central macular thickness (CMT) as measured by optical coherence tomography (OCT). The secondary outcomes were the contrast sensitivity and the damages of the retina. RESULTS: Seven studies were identified and analyzed for comparing SDM (215 eyes) with mETDRS (210 eyes) for DME. There were no statistical differences in the BCVA after treatment between the SDM and mETDRS based on the follow-up: 3mo (MD, -0.02; 95% CI, -0.12 to 0.09; P=0.77), 6mo (MD, -0.02; 95% CI, -0.12 to 0.09; P=0.75), 12mo (MD, -0.05; 95% CI, -0.17 to 0.07; P=0.40). Likewise, there were no statistical differences in the CMT after treatment between the SDM and mETDRS in 3mo (MD, -9.92; 95% CI, -28.69 to 8.85; P=0.30), 6mo (MD, -11.37; 95% CI, -29.65 to 6.91; P=0.22), 12mo (MD, 8.44; 95% CI, -29.89 to 46.77; P=0.67). Three RCTs suggested that SDM laser results in good preservation of contrast sensitivity as mETDRS, in two different follow-up evaluations: 3mo (MD, 0.05; 95% CI, 0 to 0.09; P=0.04) and 6mo (MD, 0.02; 95% CI, -0.10 to 0.14; P=0.78). Two RCTs showed that the SDM laser treatment did less retinal damage than that mETDRS did (OR, 0.05; 95% CI, 0.02 to 0.13; P<0.01). CONCLUSION: SDM laser photocoagulation shows an equally good effect on visual acuity, contrast sensitivity, and reduction of DME as compared to conventional mETDRS protocol with less retinal damage.     

糖尿病黄斑水肿患者视觉相关生活质量的调查

目的：评估伴有糖尿病黄斑水肿（DME）的2 型糖尿病患者的视觉相关生活质量（VRQoL）。方法：横 断面调查研究。将2017 年6 月至2019 年5 月从抚顺市眼病医院门诊招募的伴有DME的2 型糖尿病患 者（187 例）纳入研究。采用美国国立眼科研究院视功能问卷（NEI-VFQ-25）中文版量表来评估患者 的VRQoL。不同人口学特征、临床特征的DME患者间NEI-VFQ-25分数比较采用Wilcoxon秩和检验。 根据眼底照相将DME分为轻度、中度和重度。采用广义估计方程探讨DME严重程度与VRQoL的相 关性。结果：最终纳入DME患者159 例。伴视力损害患者的一般视力、近距离活动、远距离活动、 社交功能、依赖性、心理健康、角色困难、色觉、周边视觉和NEI-VFQ-25总分分数较无视力损害（小 数视力>0.3）患者低（均P<0.001）。双眼受累患者的一般健康、一般视力、近距离活动、远距离活动、 依赖性、心理健康、角色困难、驾驶、色觉、周边视野和NEI-VFQ-25 总分分数较单眼受累患者低 （均P<0.05）。随着DME严重程度的增加，一般健康（P趋势=0.013）、总体视力（P趋势<0.001）、近距离活 动（P趋势=0.001）、远距离活动（P趋势=0.002）、依赖性（P趋势=0.023）、心理健康（P趋势=0.001）、社会角色 （P趋势=0.022）、周边视野（P趋势=0.041）、NEI-VFQ-25总分（P趋势=0.001）的得分逐渐降低。NEI-VFQ-25 问卷中得分下降最多的是心理健康（β=-15.01，95%CI：-26.73～-3.30，P=0.012）和总体视力 （β=-13.66，95%CI：-19.86～-7.47，P<0.001）。结论：DME对VRQoL有明显的影响。随着DME严重 程度增加，VRQoL逐渐降低，尤其在总体视力和心理健康方面最为明显。     

Laser therapy versus intravitreal injection of anti-VEGF agents in monotherapy of ROP:a Meta-analysis

AIM:To compare the efficacy and safety between laser therapy and anti-vascular endothelial growth factor(VEGF)agents intravitreal injection monotherapy in type-1 retinopathy of prematurity(ROP)and aggressive posterior retinopathy of prematurity(APROP).METHODS:A systematic literature search was performed in PubMed,Cochrane Library,and Embase for original comparable studies.We included studies that compare laser therapy and intravitreal injections of anti-VEGF agents monotherapy in ROP regardless of languages and publication types.RESULTS:Complication incidence was significantly higher in laser therapy group(OR:0.38;95%CI:0.19-0.75;P=0.005).Spherical equivalent(SE)was higher in laser therapy[weighted mean difference(WMD):2.40,95%CI:0.88-3.93;P=0.002].The time between treatment and retreatment was longer in laser therapy group(WMD:8.45,95%CI:5.35-11.55;P<0.00001).Recurrence incidence(OR:0.97;95%CI:0.45-2.09;P=0.93)and retreatment incidence(OR:1.24;95%CI:0.56-2.73;P=0.59)were similar in two approaches.Subgroup analysis between type-1 ROP and APROP was not significant except SE reported in the included studies(P<0.0001).CONCLUSION:This Meta-analysis outcome indicates anti-VEGF agents are as effective as laser treatment,and safer than laser in type-1 ROP and APROP.The degree of myopia in APROP is higher than type-1 ROP.More randomized controlled trials in large sample size should be conducted in the future.     

糖化血红蛋白与糖尿病视网膜病变的关系：北京社区糖尿病研究 18

目的 探讨糖化血红蛋白（HbA1c）与糖尿病视网膜病变（DR）的关系及其诊断阈值。设计 以社区人群为基础的横断面研究。研究对象 北京社区糖尿病研究中2642例20~80岁已确诊的2型糖尿病患者,其中2007例（76.0％）受试者（1199例女性）参与研究,平均年龄（64.1±9.0）岁。方法 全体参与医师经过专门培训,按照统一要求调查并填写调查表,同时对患者进行体格检查及相关的实验室检查,HbA1c用美国伯乐公司高压液相仪测定,并对所有患者用45°免散瞳彩色眼底照相机留取后极部眼底照片一张。DR的严重程度参照Airlie House分级法。采用 ROC 曲线分析HbA1c诊断DR的最佳阈值。主要指标 HbA1c在DR中的诊断阈值（敏感性、特异性、AUC）。结果 本人群中DR患病率为（24.7±1.0）％（95％CI,22.8~26.6）。在二元逻辑回归分析中,DR的出现与较高的HbA1c浓度（OR=1.23;95％CI,1.14~1.33）有关,随着HbA1c增高,DR患病率呈上升趋势。当HbA1c≥6.5%时,诊断DR的ROC曲线下面积最大（59.2%）,且敏感性（75.1%）和特异性（43.4%）高。在二元逻辑回归分析中,DR还与其他方面有关：较轻的年龄（OR=0.97;95％CI,0.95~0.98）、较长的糖尿病病程（OR=1.10;95％CI,1.08~1.12）、较高的收缩压（OR=1.01;95％CI,1.01~1.02）、较低的体重指数（OR=0.95;95％CI,0.92~0.98）和升高的血尿素氮浓度（OR=1.01;95％CI,1.00~1.01）。结论 当糖化血红蛋白≥6.5%时与糖尿病视网膜病变显著相关,提示糖化血红蛋白为6.5%或许可以作为筛查糖尿病视网膜病变的阈值。（眼科,2016,25： 321-325）     

Computer aided diabetic retinopathy detection based on ophthalmic photography: a systematic review and Meta-analysis

AIM: To ensure the diagnostic value of computer aided techniques in diabetic retinopathy (DR) detection based on ophthalmic photography (OP). METHODS: PubMed, EMBASE, Ei village, IEEE Xplore and Cochrane Library database were searched systematically for literatures about computer aided detection (CAD) in DR detection. The methodological quality of included studies was appraised by the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-DiSc was utilized and a random effects model was plotted to summarize data from those included studies. Summary receiver operating characteristic curves were selected to estimate the overall test performance. Subgroup analysis was used to identify the efficiency of CAD in detecting DR, exudates (EXs), microaneurysms (MAs) as well as hemorrhages (HMs), and neovascularizations (NVs). Publication bias was analyzed using STATA. RESULTS: Fourteen articles were finally included in this Meta-analysis after literature review. Pooled sensitivity and specificity were 90% (95%CI, 85%-94%) and 90% (95%CI, 80%-96%) respectively for CAD in DR detection. With regard to CAD in EXs detecting, pooled sensitivity, specificity were 89% (95%CI, 88%-90%) and 99% (95%CI, 99%-99%) respectively. In aspect of MAs and HMs detection, pooled sensitivity and specificity of CAD were 42% (95%CI, 41%-44%) and 93% (95%CI, 93%-93%) respectively. Besides, pooled sensitivity and specificity were 94% (95%CI, 89%-97%) and 87% (95%CI, 83%-90%) respectively for CAD in NVs detection. No potential publication bias was observed. CONCLUSION: CAD demonstrates overall high diagnostic accuracy for detecting DR and pathological lesions based on OP. Further prospective clinical trials are needed to prove such effect.     

Effectiveness of intravitreal ranibizumab for diabetic macular edema in vitrectomized versus non-vitrectomized eyes: a Meta-analysis

AIM: To evaluate the effectiveness and safety of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) in vitrectomized versus non-vitrectomized eyes. METHODS: The PubMed, EMBASE, Web of Science, Cochrane, EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME. Clinical outcomes of best-corrected visual acuity (BCVA), central macular thickness (CMT), the mean number of intravitreal injection and adverse events were extracted and analyzed. RESULTS: Six studies involving 641 eyes were included. Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits (P<0.05). Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo [mean difference (MD)=53.57, 95% confidence interval (CI): 28.03 to 78.72, P<0.0001] and 12mo (MD=49.65, 95%CI: 19.58 to 79.72, P=0.01), no significant difference was detected in improvement in BCVA at either 6mo (MD=0.05, 95%CI: -0.02 to 0.13, P=0.14) or 12mo (MD=0.03, 95%CI: -0.04 to 0.09, P=0.43). Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period (MD=0.60, 95%CI: 0.16 to 1.04, P=0.008), while there was no statistically significant difference between the two groups during 12mo of follow-up. CONCLUSION: Evidence from current study suggests that IVR was useful for both vitrectomized group and non-vitrectomized group with DME. Although less reduction in macular thickness is found in vitrectomized group, visual improvement between two groups is similar.     

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis

AIM: To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). METHODS: Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. RESULTS: Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. CONCLUSION: The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).     

Inhibition of TGF-β2-induced migration and epithelial-mesenchymal transition in ARPE-19 by sulforaphane

AIM: To investigate the effects of sulforaphane (SFN) on transforming growth factor (TGF)-β2 stimulated migration and epithelial-mesenchymal transition (EMT) in ARPE-19 cells. METHODS: ARPE-19 cells were cultured in the presence or absence of SFN or TGF-β2. SFN toxicity was assessed by performing a lactate dehydrogenase assay (LDH) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, and cell migration was evaluated by Transwell migration assay. Actin stress fiber formation in ARPE-19 cells was determined using immunofluorescence analysis. Immunoblotting analysis was used to determine fibronectin and α-smooth muscle actin expressions along with the degree of Smad and Akt phosphorylation. RESULTS: SFN inhibited ARPE-19 migration. Additionally, SFN attenuated TGF-β2-induced appearance of actin stress fibers as well as fibronectin and α-smooth muscle actin expressions in these cells. SFN also hindered the TGF-β2-stimulated phosphorylation of Smad2, Smad3, and Akt. SFN showed no cytotoxicity towards ARPE-19 cells. CONCLUSION: SFN inhibits TGF-β2-stimulated migration and EMT in ARPE-19 cells, probably by preventing the establishment of actin stress fibers and Akt and Smad2/3 signaling.     

Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

AIM:To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism (rs5498) with diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM).METHODS:Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs). Potential sources of heterogeneity and bias were explored.RESULTS:Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469E polymorphism with DR (P>0.05). A statistically significant association was detected between the K469E polymorphism and proliferative diabetic retinopathy (PDR) in Asians only in dominant model (GG+AG vs AA) with pooled OR of 0.729 (95%CI:0.564-0.942, P=0.016, Pheterogeneity=0.143), however, this association was not detected in recessive model (GA+AA vs GG; OR=1.178, 95%CI:0.898-1.545, P=0.236, Pheterogeneity=0.248) or allelic model (G vs A; OR=0.769, 95% CI:0.576-1.026, P=0.074, Pheterogeneity=0.094). No publication bias was found by Funnel plot, Begg's and Egger's test.CONCLUSION:This research found no statistically significant association between ICAM-1 gene K469E polymorphism and DR in patients with T2DM, but showed significant association of the K469E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.