Subthreshold micropulse laser versus intravitreal anti-VEGF for diabetic macular edema patients with relatively better visual acuity

AIM:To compare the effects of yellow(577 nm)subthreshold micropulse laser(SML)and intravitreal(IV)anti-vascular endothelial growth factor(VEGF)treatment in patients with diabetic macular edema(DME)with relatively better visual acuity[best corrected visual acuity(BCVA)≤0.15 log MAR].METHODS:The medical records of 76 eyes of 47 patients underwent IV(0.5 mg)anti-VEGF injection or SML for the DME with relatively better BCVA were reviewed.The IV group received three consecutive monthly IV anti-VEGF injections,then were retreated as needed.The laser treatment group was treated at baseline and 3 mo,and then retreated at 6 and 9 mo if needed.All participants were followed up for one year.The mean BCVA and mean central macular thickness(CMT)values changes over the follow-up were evaluated.RESULTS:Twenty-four and 23 patients were assigned to the SML and IV subgroups,respectively.The mean number of treatments was 3.64±0.76 in SML group and 5.85±1.38 in IV group(P<0.05).The subgroups were similar with regard to the mean BCVA score at baseline and at the 1st and 3rd months,but the score of SML group was better than that of IV group at the 6th,9th,and 12th months(P<0.05).The decrease in the mean CMT values from baseline values was higher in SML group at the 6th,9th,and 12th months(P<0.05).CONCLUSION:Yellow SML treatment is superior to IV anti-VEGF injection in DME patients with relatively better BCVA for increasing visual acuity and decreasing CMT at 6,9,and 12 mo.SML can be a good alternative first-line therapy for DME with BCVA≤0.15 log MAR.

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion

AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twenty-eight eyes from twenty-eight treatment-na?ve patients(14 males and 14 females) with RVO-ME were included in this retrospective study.The retinal vein occlusion(RVO) was comprised of both central retinal vein occlusion(CRVO,n=14) and branch retinal vein occlusion(BRVO,n=14).Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months,in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept.All eyes were imaged with optical coherence tomography angiography(OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection.The visual acuity(VA),central macular thickness(CMT),the number of hyperreflective foci(HRF) recognized as an inflammatory sign in OCT images,and non-perfusion area(NPA),were compared before and after anti-VEGF treatments.RESULTS: The mean interval between baseline and follow-up was 29.4±0.79(range,27-48)d.Compared with the baseline,the VA improved(log MAR 1.5±0.1 vs 0.8±0.1,P<0.05) and CMT decreased(460±34.0 μm vs 268.8±12.0 μm,P<0.05),significantly,after antiVEGF treatment.The number of HRF was decreased significantly(76.5±4.8 vs 47.8±4.3,P<0.05) after antiVEGF treatment.CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME.The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

AIM: To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). ·METHODS: This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus TM ); IOP measurements were taken 30 minutes and 24 hours after each injection. RESULTS: The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P =0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P = 0.07) over (13.6±2.1) and (14.05±2.6) months (P =0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3± 6.9μm and 74.4±11.2μm) were not different from those in untreated eyes in the IVR group (104.6±8.4μm and 75.1±12.6μm) (P =0.57 and P =0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1μm and 74.5±11.8μm) were not different from those in untreated eyes in the IVB group (104.6±8μm and 74.8±12.9μm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P =0.16) were comparable between groups. CONCLUSION: Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.

Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients

AIM: To analyze concentrations of vascular endothelial growth factor(VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy(PDR) patients pretreated with intravitreal anti-VEGF injections(IVI) at different time periods prior to pars plana vitrectomy(PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI.METHODS: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDRrelated complications(PDR group) and 21 eyes with nondiabetic ocular disease(control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3 d after IVI(3-day group);5 d after IVI(5-day group);7 or more days after IVI(≥7-day group);and no IVI. Vitreous fluid samples(0.5-1.0 m L) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor(b FGF), periostin(PN), interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis.RESULTS: PDR eyes without IVI had significantly higher VEGF, b FGF, PN, and IL-6 concentrations than nondiabetic eyes(all P<0.05), and had a significantly higher concentration of VEGF(P<0.05) and a significantly lower concentration of IL-8(P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, b FGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups(all P<0.05);meanwhile there was no significant difference in TNF-α among groups(P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of b FGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day(P=0.015) and 5-day group(P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of b FGF, PN, IL-6, and IL-8(all P<0.05). Univariate ordinal logistic regression analysis showed that b FGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI.CONCLUSION: The vitreous concentrations of VEGF, b FGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angiofibrosis switch. The results suggest that PPV should be performed 5 d after IVI administration in PDR patients.

Recent advances and future directions for the pharmacogenetic basis of anti-VEGF treatment response in neovascular age-related macular degeneration

Age related macular degeneration （AMD） is a complex progres- sive neurodegenerative disease causing blindness in 30-35 million people worldwide. It affects the macula region of the retina leading to severe vision loss and legal blindness in individuals 〉 50 years of age （Wong et al., 2014）. The precise aetiology of AMD is unknown but smoking, age and genetic factors are major risk factors for AMD predisposition （Ding et al., 2009）. The genetic basis of AMD is well described with a recent study from the International AMD gene consortium （IAMDGC） reporting 52 genetic variants across 34 loci associated with the risk of AMD pathogenesis and explaining more than 50% of the genetic heritabilitv of the disease （Fritsche et al., 2016）.

Efficacy of Anti-VEGF and Subtenon Injection of Triamcinolone Acetonide for Choroidal Neovascularization Associated with Multifocal Choroiditis

Purpose: To evaluate the short-term efficacy of intravitreal anti-VEGF (Lucentis) and sub-tenon injection of triamcinolone acetonide for choroidal neovascularization (CNV) associated with multifocal choroiditis (MC). Methods: Eight eyes of 8 patients treated with intravitreal anti-VEGF and posterior sub-tenon injection of Triamcinolone Acetonide (TA) for subfoveal or juxtafoveal CNV associated with MC were retrospectively reviewed. Best corrected visual acuity (BCVA), results of fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA), optical coherence tomography (OCT) at baseline and 3, 6 months after treatment were compared. Results: All of the 8 patients showed significant improvement in BCVA at 3 and 6 months after treatment (P < 0.05). FFA/ICGA showed decrease or cessation of inflammation in 8 patients (100%). 7 patients (87.5%) had no significant active leakage while 1 patient (12.5%) had persistent leakage from the neovascular lesion at 3-month follow up. 6 months after treatment, no recurrence of inflammation occurred and no active leakage in all 8 patients. OCT showed reduced CNV area and alleviated edema. There are no severe treatment-related side effects expect slight eye pain during infusion in one patient. Intraocular pressure was all normal in follow up. Conclusion: Although the follow-up time and the number of patients in this study were limited, the use of intravitreal anti-VEGF combined with sub-tenon injection of TA was associated with improvement of visual acuity in patients with CNV secondary to MC. Further studies including a greater number of patients with longer follow up time are needed.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(RNFL)thickness in wet age-related macular degeneration(AMD)patients.

关节腔内注射Anti-VEGF对家兔TMJ间接性损伤作用研究

目的:研究应用拮抗血管形成因子试剂对于减轻TMJ(Temporomandibular joint)间接性损伤后软骨破坏效果的影响。方法:应用关节病理损伤指数、关节滑膜血管密度积分和关节软骨含量等检测实验组和对照组组织损伤情况。结果:4周及8周实验组软骨含量均高于对照组,两者比较差异有显著性(P<0.05);4周及8周对照组的关节病理损伤指数均高于实验组,差异具有显著性(P<0.05);4周及8周的关节滑膜血管密度积分低于对照组,差异具有显著性(P<0.05)。结论:应用拮抗血管生成剂可显著提高TMJ间接损伤的关节软骨含量,减少新生的血管形成及减轻TMJ间接损伤后关节内炎症。

Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)therapy.Methods Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively included.Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment strategy.OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months.CNV lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and non-responders.Two masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)values.Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF agents.Results Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were non-responders.The proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF injections.Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy.Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.

Outcomes of vitrectomy,complete pan-retinal photocoagulation,and endoscopic cyclophotocoagulation surgery after anti-VEGF treatment in neovascular glaucoma

Purpose:To establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor(VEGF)injection,pars plana vitrectomy(PPV),endoscopic pan-retinal photocoagulation(PRP),and endoscopic cyclophotocoagulation(ECP)surgery for neovascular glaucoma(NVG)patients.Methods:This retrospective study included 30 patients(30 eyes)who were suffering from NVG and treated with PPV&PRP&ECP(ECP group,16 eyes),or Ahmed glaucoma valve implantation(Ahmed group,14 eyes).The intraocular pressure(IOP),number of postoperative anti-glaucoma medications,best-corrected visual acuity(BCVA),successful rate of surgery,and postoperative complications were recorded and statistically analyzed at the time points of preoperative,1-day,1-month,3-months,6-months,and 12-months after operation.Results:An obvious reduction in IOP and number of postoperative anti-glaucoma medications were observed in both the ECP group and Ahmed group after operation(P<0.05),and the ECP group showed a significantly lower IOP compared to the Ahmed group at the 6-months(P=0.014)and 12-months(P=0.047)postoperative time points,while there was no significant difference of medication number between the two groups except for 1-day after surgery.The BCVA showed no marked difference between the two groups preoperatively and postoperatively(P>0.05),while it was significantly improved in ECP group at 3-months(P=0.001),6-months(P=0.004),and 12-months(P=0.010)time points comparing with preoperative BCVA.The surgical success rates in ECP group were also slightly higher than Ahmed group.And the complications after operation showed no marked differences.Conclusions:The comprehensive treatment of PPV,endoscopic PRP,and ECP surgery for NVG patients after antiVEGF injection can control IOP effectively and be friendly to patients’BCVA without obvious serious complications throughout a 12-months follow-up period.

关注新生血管性年龄相关性黄斑变性的创新药物治疗

湿性年龄相关性黄斑变性(nAMD)是老年人致盲的主要原因,抗VEGF是其主要治疗方法。目前,nAMD治疗仍面临诸多不足和挑战,开发新的治疗药物和给药方法是其主要研究的方向。近年来治疗nAMD的药物研发方向呈现多样化,包括开发新靶点/新机制药物及新型给药方式、优化给药剂量和基因疗法等,达到降低治疗频率、延长治疗间隔、提高患者治疗依从性和长期维持或改善视力的目的。眼科临床医师应对新的药物有较为全面的了解,进而发掘出适合不同nAMD亚型患者的优化方案,实现向精准化医疗迈进。

超声乳化联合玻璃体注射抗VEGF药治疗白内障合并黄斑水肿的应用

目的观察白内障超声乳化联合玻璃体腔注射抗血管内皮生长因子(VEGF)药物治疗白内障合并各种黄斑水肿的临床效果。方法回顾性病例对照研究。选取眼科2019年1月至2022年12月期间眼科住院白内障合并各种黄斑病变(糖尿病性黄斑水肿,年龄相关性黄斑变性),高度近视脉络膜新生血管(CNV)20例(20只眼),随机分成两组,A组(10例)给予白内障超声乳化吸除联合人工晶状体植入术,术中联合玻璃体内抗VEGF药物注射,B组(10例)行白内障超声乳化联合人工晶状体植入术。随访1个月,观察两组之间治疗前后:前房及玻璃体情况、最佳矫正视力(BCVA)、黄斑中心凹厚度(CMT)、眼压的差异。结果A组术后CMT及眼压较术前降低,和B组比较差异有统计学意义(P<0.05)。两组术后BCVA都较术前提高,A组明显好于B组,差异有统计学意义(P<0.05)。结论白内障超声化术联合玻璃体抗VEGF药物,治疗白内障合并黄斑水肿应用安全有效,值得推广。

抗VEGF药物联合全视网膜光凝治疗糖尿病视网膜病变的效果和预后分析

目的探讨抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物联合全视网膜光凝(panretinal photocoagulation,PRP)治疗糖尿病视网膜病变的效果和预后分析。方法选取三明市第二医院2020年1月—2023年1月收治的50例糖尿病视网膜病变者(78眼),以随机数字表法分为2组,各25例(39眼)。对照组患者给予PRP治疗,研究组给予抗VEGF药物联合PRP治疗。比较2组术前、术后恢复指标,统计患者治疗后的不良反应,评价治疗效果。结果术后,2组最佳矫正视力(best correct vision acuity,BCVA)优于术前,视网膜新生血管(retinal neovascularization,RNV)面积、中央视网膜厚度(central retinal thickness,CRT)低于术前,且研究组BCVA高于对照组;RNV面积、CRT低于对照组,差异有统计学意义(P<0.05);研究组并发症总发生率为5.13%,低于对照组的23.08%,差异有统计学意义(P<0.05);研究组治疗总有效率为94.97%,高于对照组的79.49%,差异有统计学意义(P<0.05)。结论糖尿病视网膜病变以抗VEGF药物联合PRP治疗可改善术后BCVA,减少RNV面积、CRT,降低并发症发生率,提升治疗效果。

高度近视继发黄斑新生血管抗VEGF术后患者近期视力预后相关因素分析

目的探讨影响抗血管内皮细胞生长因子(VEGF)治疗高度近视继发黄斑新生血管(MNV)患者近期视力预后的相关因素。方法回顾性分析2021年1月至2023年6月在安徽理工大学第一附属医院眼科接受抗VEGF治疗的高度近视继发MNV患者28例(28只眼)的临床资料。以术后1个月最佳矫正视力(BCVA)分为视力预后不良组和视力预后良好组,对比两组患者术前眼部特征及相关生物参数并进行统计学分析。结果高度近视继发MNV患者抗VEGF治疗1个月后BCVA、黄斑中心凹厚度(CMT)、MNV面积,较术前均显著改善,差异均有统计学差异(Z=6.371,6.949,2.437,均P<0.05)。单因素分析显示,两组患者在眼轴长度、后巩膜葡萄肿、CMT改善、MNV面积改善上差异均有统计学意义(均P<0.05)。多因素Logistic回归分析显示,眼轴长度和术前MNV面积是影响MNV患者抗VEGF治疗后视力预后的独立影响因素(均P<0.05)。结论抗VEGF治疗高度近视继发MNV可有效提高患者视力,术后视力与眼轴长度、后巩膜葡萄肿、CMT改善、MNV面积改善相关,其中,眼轴长度和术前MNV面积是影响视力预后的独立影响因素。

缺血性视网膜静脉阻塞继发黄斑水肿患者基线血清己糖激酶1抗体滴度与抗VEGF治疗后视力改善的相关性分析

目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。

PD-1/PD-L1抑制剂联合抗血管内皮生长因子药物免疫治疗晚期肝癌的研究进展

肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。

Ozurdex与抗VEGF药物对糖尿病性黄斑水肿的疗效分析

目的比较Ozurdex与抗血管内皮生长因子(VEGF)药物对糖尿病性黄斑水肿(DME)的疗效。方法回顾性病例分析研究。收集2020年1月至2023年3月期间在安徽理工大学第一附属医院(淮南市第一人民医院)眼科进行玻璃体腔药物注射的DME患者23例(28只眼)。根据患者选择的治疗方案及注药的规律性分为三组:抗VEGF1组:患者玻璃体内注射抗VEGF药物(雷珠单抗、康柏西普、阿柏西普)0.05 ml,每月规律注射,连续注射3次,总治疗时间为12周,共7例(9只眼);抗VEGF2组:患者玻璃体内注射抗VEGF药物(0.05 ml),连续注射3次,注射不规律,两次注射之间间隔时间4~6周,总治疗时间在12~14周,共8例(10只眼);玻璃体内地塞米松植入(IDI)组:患者进行一次玻璃体内注射Ozurdex(0.7 mg),共8例(9只眼)。利用频域相干光层析成像术(SD-OCT)监测三组患者16周内黄斑中心凹视网膜厚度(CMT)的变化情况。结果IDI组与抗VEGF1组12周内CMT明显下降且下降程度相当,均值均小于300μm;抗VEGF2组CMT在12~14周内CMT处于波动中,且均值高于300μm;IDI组CMT在治疗后8周内持续下降,8周时达最低值,12周时CMT略回升;抗VEGF1组在治疗后12周内CMT持续下降,治疗16周后三组CMT均恢复至较高水平(高于300μm),均需再治疗。结论Ozurdex与抗VEGF药物均可明显改善DME患者黄斑中心凹的解剖形态,Ozurdex可在12周内稳定的维持黄斑部较正常的解剖学形态,抗VEGF药物疗效需依赖患者的依从性,按时复诊治疗的患者可在12周内维持较为良好的黄斑部解剖学形态。

Potent anti-angiogenesis and anti-tumor activity of a nove human anti-VEGF antibody, MIL60

Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor （VEGF） has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin （the KD value of MIL60 was 44.5 pM, while that of Avastin was 42.7 pM）. MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation （the IC5o value of M IL60 was 31-6.4 ng/ml and that of Avastin was 47--.8.1 ng/ml）, migration （8 pg/ml or 0.8 pg/ml MIL60 versusthe control： P〈O.05） and tube formation （2 I^g/ml or 0.2 lzg/ml MIL60 versusthe control： P〈O.05） viathe VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis （MIL60 versus N.S.： P=0.0007; Avastin versus N.S.： P=0.00046）. These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.

Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy

Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA were based on the following parameters:branching,vessel caliber and area of adjacent capillary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44%)remained unchanged,six IRMAs(13%)progressed with enlargement or development of new IRMAs and five IRMAs(11%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMA(63%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The difference in rank order between the two groups was statistically significant(p=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stabilit,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.