Diabetic macular edema:Efficacy and safety of antivascular endothelial growth factor therapy

Diabetic retinopathy is one of the prominent causes of vision impairment in the working-age population in industrialized countries and is related to 1%-5% of cases of blindness in the world. Among patients with diabetic retinopathy, diabetic macular edema(DME) is the major reason of vision impairment and represents a significant public health problem. Previous studies demonstrated the role of vascular endothelial growth factor(VEGF) in diabetic retinopathy and DME pathogenesis, and also revealed the efficacy of anti-VEGF agents for the management of these disorders. This review summarizes the outcomes of clinical studies that evaluated the anti-VEGF therapy including pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. A significant number of clinical trials indicated favorable functional and anatomical results of anti-VEGF therapy for DME. Therefore, these agents should be considered an option in the treatment of DME in routine clinical practice.

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 Pub Med, EMBASE, Web of Science, Cochrane Library, and Clinical Trials.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 24 mo after initial treatment, and the risk ratios(RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12 mo. 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 12 mo 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 ofpatients 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).

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM: To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema(DME) resistant to anti-vascular endothelial growth factor(VEGF) therapy.METHODS: Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant(Ozurdex~) was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity(BCVA) measured with Early Treatment Diabetic Retinopathy Study(ETDRS) and central macular thickness(CMT) exams were carried out at baseline(T0)and after 1(T1),3(T3),4(T4),6(T6),9(T9),12(T12),15(T15),and 18mo(T18) post injection. RESULTS: Repeated measures ANOVA showed an effect of treatment on ETDRS(P<0.0001).Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15(P <0.001) as compared to baseline value(T0).At T6,T12,and T18,ETDRS values were still statistically higher than baseline(P<0.001 vs T0).However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment(P <0.0001).CMT decreased significantly at T1,T3,T4,T9,and T15(P<0.001).At T6(P<0.01),T12 and T18(P<0.001) CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION: Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Current status in diabetic macular edema treatments

Diabetes is a serious chronic condition,which increase the risk of cardiovascular diseases,kidney failure and nerve damage leading to amputation.Furthermore the ocular complications include diabetic macular edema,is the leading cause of blindness among adults in the industrialized countries.Today,blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy.The treatment should include an optimized control of glycemia,arterial tension,lipids and renal status.The photocoagulation laser is currently restricted to focal macular edema in some countries,but due the high cost of intravitreal drugs,the use of laser treatment for focal and diffuse diabetic macular edema(DME),can be valid as gold standard in many countries.The intravitreal anti vascular endothelial growth factor drugs(ranibizumab and bevacizumab),are indicated in the treatment of all types of DME,but the correct protocol for administration should be defined for the different Retina Scientific Societies.The corticosteroids for diffuse DME,has a place in pseudophakic patients,but its complications restricted the use of these drugs for some patients.Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.

Diabetic macular edema:Current management 2013

Diabetic retinopathy(DR)is the leading cause of vision loss of working-age adults,and diabetic macular edema(DME)is the most frequent cause of vision loss related to diabetes.The Wisconsin Epidemiologic Study of Diabetic Retinopathy found the 14-year incidence of DME in type 1 diabetics to be 26%.Similarly the Diabetes Control and Complications Trial reported that 27% of type 1 diabetic patients develop DME within9 years of onset.The most common type of diabetes,type 2,is strongly associated with obesity and a sedentary lifestyle.An even higher incidence of macular edema has been reported in older patients with type 2diabetes.Within the last 5 years,the use of intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor(VEGF)agents have come into clinical practice for the management of DME and several recent randomized clinical trials have shown improved effectiveness of ranibizumab compared to focal/grid laser.In this theme issue,we discuss the classification of DR and the treatment options currently available for the treatment of DME including corticosteroids,anti-VEGF agents,combined therapy,enzymatic vitrectomy(vitreolysis),and new therapies.

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.

Treatment for diabetic macular oedema:looking further into the evidence

Throughout the years,people with diabetic macular oedema(DMO)have seen the number of options for their treatment increasing.Laser photocoagulation was the first of these and great experience is behind it;intraocular steroids followed and more recently anti-vascular endothelial growth factor(anti-VEGF)agents came to light.Ophthalmologists face now the dilemma of determining which may be the best therapeutic strategy for each particular patient based on best available evidence.This article summarises data available from randomised clinical trials(RCTs)on treatments for DMO and provides some facts about this condition and its treatments that need to be taken into consideration when treatment decisions are made.

Progress in the Treatment of DME

Diabetic macular edema (DME) is a common ocular complication of diabetes mellitus (DM) and an important cause of vision loss. The pathogenesis of DME is complex and can occur at any time of diabetic retinopathy (DR). Effective methods of treating DME are essential to prevent irreversible damage to visual function. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated their therapeutic efficacy in large randomized controlled trials and real-life observational studies. Clinicians need to consider various factors, such as efficacy, safety, accessibility, and cost, in the selection of various options. This review summarizes the current therapeutic approaches for DME to provide new references for the treatment of DM.

单独雷珠单抗玻璃体内注射与联合激光疗法治疗DME疗效和安全性meta分析

目的评估玻璃体内注射雷珠单抗联合激光光凝(IVR+Laser)与单用玻璃体内注射雷珠单抗(IVR)治疗糖尿病性黄斑水肿(DME)的疗效和安全性。方法采用meta分析方法,检索有关IVR+Laser疗法与单用IVR治疗DME的随机对照试验(RCT)文献进行二次分析,检索文献范围包括Cochrane Library、PubMed、EMbase、Web of Science、中国生物医学文献数据库、中国知网、维普网、万方数据,检索时间均从建库起至2022年4月。由2位研究员按照纳入和排除标准独立进行文献筛选、资料提取、质量评价并交叉核对后,采用RevMan5.4.1软件进行meta分析,比较不同方法治疗后最佳矫正视力(BCVA)、黄斑中心凹厚度(CMT)、平均注射次数和不良事件的差异。结果共纳入12篇RCT,共1695眼。meta分析结果显示,随访结束时,IVR+Laser组患者BCVA和CMT改善情况优于IVR组,2个组BCVA变化和CMT变化差异均有统计学意义(WMD=-0.66,95%CI:-1.11~-0.21,P<0.01;WMD=-5.05,95%CI:-9.21~-0.89,P=0.02)。随访结束时,IVR+Laser组平均注射次数明显少于IVR组,差异有统计学意义(WMD=-1.16,95%CI:-2.07~-0.25,P=0.01)。2个组不良事件发生率比较,差异均无统计学意义(均P>0.05)。结论IVR+Laser联合治疗DME疗效优于单独IVR治疗,安全性与单独IVR治疗相当,且平均注射次数较少。

糖尿病黄斑水肿抗血管内皮生长因子治疗进展

糖尿病黄斑水肿(DME)是导致糖尿病患者视功能损伤的主要原因之一,DME的治疗方法包括激光光凝治疗、抗炎治疗和抗血管内皮生长因子(VEGF)治疗。近年来,抗VEGF药物Ranibizumab、Bevacizumab、VEGF-Trap和KH902等对DME有良好的治疗效果。文章对DME抗VEGF治疗进展进行综述,探讨抗VEGF治疗的有效性和安全性。

糖尿病黄斑水肿治疗方案的选择及需要关注的几个问题

糖尿病黄斑水肿（DME）是引起糖尿病患者视力障碍的常见原因，DME易复发，治疗效果不尽如人意，其治疗研究的进展一直受到眼科医师的关注。目前，在国内外关于DME的治疗指南中均已将抗血管内皮生长因子（VEGF）疗法作为一线的或核心的治疗方法，该疗法在临床上已广泛使用。但在临床实践中我们发现，DME治疗方法的选择和实施仍有不明确之处，同时也存在一定的争议，包括DME的治疗目标、疗效的判断指标、对国内外指南的解读、抗VEGF疗法的实施方案、传统激光光凝的作用和临床价值、糖皮质激素类药物的应用方法、复发性DME的处理原则等。近年来针对DME治疗的药物研究仍在进行并取得了一定进展，只有跟踪相关的研究成果，不断完善DME的治疗方法，充分了解不同药物和不同治疗方案的优势和缺点，规范治疗流程，才能最大程度地发挥各种治疗方法或联合疗法对DME的治疗作用。

雷珠单抗联合577nm微脉冲激光治疗重度糖尿病性黄斑水肿

目的:观察雷珠单抗联合577nm微脉冲激光治疗重度糖尿病性黄斑水肿(DME)的临床疗效。方法:选取2016-06/2019-09就诊于广西壮族自治区人民医院确诊为重度DME的患者52例52眼,随机分为观察组(26例26眼,予雷珠单抗联合577nm微脉冲激光治疗)和对照组(26例26眼,仅予雷珠单抗治疗)。两组患者均予“3+PRN”方案行玻璃体腔注射雷珠单抗治疗。治疗(首次玻璃体腔注射)后随访9mo,观察黄斑中心凹厚度(CMT)、最佳矫正视力(BCVA)情况及玻璃体腔注射雷珠单抗次数。结果:与治疗前相比,两组患者治疗后各时间点CMT、BCVA均明显改善(均P<0.001),但两组间均无差异(P>0.05)。随访期间,观察组玻璃体腔雷珠单抗注射次数明显少于对照组(5.88±1.24次vs 7.12±1.24次,P=0.001)。结论:雷珠单抗联合577nm微脉冲激光和单用雷珠单抗均能有效降低重度DME患者黄斑水肿程度,改善视力,但联合治疗可减少雷珠单抗的注射次数。

雷珠单抗联合微脉冲激光治疗糖尿病性黄斑水肿的效果及对患者血清PEDF、VEGF水平的影响

目的探讨雷珠单抗联合微脉冲激光治疗糖尿病性黄斑水肿(DME)的效果及对患者血清色素上皮衍生因子(PEDF)、血管内皮生长因子(VEGF)水平的影响。方法选取2016年6月至2019年6月杨凌示范区医院收治的DME患者92例(101只患眼),按照随机数字表法将其分为研究组(46例,51只患眼)与对照组(46例,50只患眼)。两组均采取雷珠单抗玻璃体腔内注射,在此基础上研究组采取微脉冲激光治疗,对照组采取传统激光治疗。比较两组的治疗效果。结果治疗后1、3、6个月,两组黄斑体积、黄斑中心凹厚度均较治疗前减小,视力均较治疗前升高,且研究组优于对照组(P<0.05)。治疗后,两组血清PEDF水平较治疗前升高,VEGF水平较治疗前降低,且研究组优于对照组(P<0.05)。结论雷珠单抗联合微脉冲激光治疗DME的效果显著,可减小黄斑体积、黄斑中心凹厚度,提升视力,改善血清PEDF、VEGF水平,值得临床应用和推广。