预测视网膜静脉阻塞继发黄斑水肿抗VEGF治疗后视力的形态学指标分析

目的 评价视网膜静脉阻塞（RVO）继发黄斑水肿（ME）患者抗VEGF治疗基线荧光血管造影（FFA）及相干光断层扫描（OCT）指标与患者治疗后最佳矫正视力（BCVA）的关系。设计 回顾性病例系列。研究对象 北京同仁医院连续抗VEGF治疗应答良好的125例125眼RVO继发ME患者。方法 所有患者均接受每月1次玻璃体注射雷珠单抗0.05 ml,直至ME完全消退。所有患者均采用Spectralis HRA+OCT进行FFA及OCT检查,半自动分析患者基线FFA及OCT形态学指标。采用Logtistic回归分析评价各分析因素与患者治疗后BCVA的关系。主要指标 BCVA,黄斑旁中心凹毛细血管灌注,黄斑中心视网膜厚度,黄斑中心视网膜容积,视网膜各层的完整性。结果125眼中,7眼（5.6%）基线BCVA≥0.5,抗VEGF治疗后43眼（34.4%）BCVA≥0.5。患者基线黄斑旁中心凹毛细血管无灌注（P=0.01,OR=0.213）、 内丛状层结构模糊（P=0.005,OR=0.225）、外界膜破坏（P=0.001,OR=0.160）是阻碍治疗后获得良好视力预后的主要影响因素。结论 基线FFA显示黄斑中心凹毛细血管无灌注或OCT显示黄斑中心凹区视网膜内丛状层结构模糊或外界膜破坏提示抗VEGF治疗RVO继发ME的视力预后不佳。（眼科,  2018,  27：111-115）     

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P=0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.     

VEGF对大鼠50%减体积肝脏移植术后肝再生的影响

目的探讨血管内皮生长因子(VEGF)对大鼠减体积肝移植术后肝脏再生的影响。方法建立大鼠50%减体积肝移植模型,分3组,VEGF治疗组、anti-VEGF组、对照组。分别于术后注射鼠重组VEGF、anti-VEGF、生理盐水(NaCl)。在术后不同时相点测定肝细胞核增殖蛋白抗原(PCNA)表达指数,测定血清HGFI、L-6的含量,测定术后肝脏生化指标。结果VEGF组术后肝细胞PCNA表达指数较对照组升高,anti-VEGF组较对照组降低,差异有统计学意义。anti-VEGF组天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)较VEGF组及对照组升高,差异有统计学意义。VEGF组术后血清HGFI、L-6浓度较对照组增高,anti-VEGF组较对照组明显减弱。结论VEGF治疗增强大鼠减体积肝移植术后肝脏再生活性,改善术后肝功能。这可能与VEGF促进肝脏HGFI、L-6分泌有关。     

Choroidal Changes in Eyes With Polypoidal Choroidal Vasculopathy After Anti-VEGF Therapy Imaged With Swept-Source OCT Angiography

PurposeSwept-source optical coherence tomography angiography was used to investigate choroidal changes and their association with pigment epithelial detachments (PEDs) in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors.MethodsPatients with treatment-naïve PCV were included and underwent anti-VEGF therapy. Mean choroidal thickness (MCT), choroidal vascularity index (CVI), and PED volume measurements were obtained before and after treatment.ResultsThirty-four treatment-naïve PCV eyes from 33 patients were included. The PED volume decreased after treatment (P < 0.05). The MCT decreased from 223.0 ± 79.6 µm at baseline to 210.9 ± 76.2 µm after treatment (P < 0.001). The CVI at baseline was 0.599 ± 0.024, and the CVI after treatment was 0.602 ± 0.023 (P = 0.16). There was a correlation between the decreased PED volumes and the decreased MCT measurements (r = 0.47; P = 0.006). Also, there was a correlation between the decreased PED volumes and the increased CVI measurements (r = −0.63; P < 0.001).ConclusionsIn treatment-naïve eyes with PCV, the decreases in PED volumes were correlated with the decrease in MCT and the increase in CVI measurements. We propose that, at baseline, the PCV lesions serve as high-volume arteriovenous shunts between choroidal arterial and venous circulation, causing transudation into the choroidal stroma. We propose that, after treatment, the blood flow through the vascular shunt is reduced, the excess stromal transudation is resorbed, and the exudation from the neovascular lesion is reduced, resulting in thinning of the choroid, resolution of the PEDs, and an increase in the CVI due to the resorption of excess choroidal transudation.     

Impact of systemic parameters before commencing anti-vascular endothelial growth factor therapy for diabetic macular edema – Pan-Indian survey of retina specialists

Purpose:Intravitreal anti-vascular endothelial growth factor (VEGF) injection therapy has emerged as the mainstay of treatment in the management of diabetic macular edema (DME) today. Various systemic risk factors have to be considered before initiating anti-VEGF therapy. The aim of our study was to form a consensus on various systemic factors to consider before starting anti-VEGF therapy for DME.Methods:A questionnaire was created and sent across to various retina specialists across India. A Google™ form with various questions pertaining to what systemic parameters would one consider before giving anti-VEGF therapy for DME was sent to each of them by email/WhatsApp™/direct telephonic interview.Results:Of the 650 retina specialists contacted, 322 responded to the questionnaire. There was no difference in responses between private and institutional practitioners. The majority would consider RBS (85%), HbA1c (61%), blood pressure (63%), and renal function (57%) as a routine before administering the anti-VEGF injection, while the majority would not consider hemoglobin (63%) or lipid profile (55%) of the patient as a routine practice prior to administering the injection.Conclusion:In our study, most VR specialists prefer to consider RBS, HbA1c, BP, and renal profile (creatinine) routinely prior to anti-VEGF injection. We suggest that it is important to consider blood pressure control, glycemic control, HbA1c, Hb, lipid profile, and renal profile (UACR, eGFR, and creatinine) prior to anti-VEGF therapy in all diabetic patients and to discuss the need for statins in patients with dyslipidemias with the physician.     

VEGF对大鼠50%肝脏移植术后血清HGF、IL-6浓度的影响

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)对大鼠部分肝移植术后血清肝细胞生长因子(hepatocyte growth factor,HGF)、白细胞介素-6(interleukin-6,IL-6)浓度的影响.方法 建立大鼠50%部分肝移植模型.实验动物分3组:VEGF治疗组、anti-VEGF组、对照组.分别于术后注射鼠重组VEGF、 anti-VEGF、生理盐水.在术后不同时相点(0、12、24、72、168 h)测血清中HGF、IL-6 含量及肝脏生化指标.结果 VEGF组血清HGF、IL-6水平较对照组明显增高,anti-VEGF组较对照组明显降低,有显著差异.anti-VEGF 组天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanine aminotransferase,ALT)较VEGF组及对照组明显升高,有显著差异.结论 VEGF治疗能明显促进大鼠部分肝脏移植术HGF、IL-6的释放.     

外层视网膜管型在nARMD中的发生率及其对抗VEGF治疗注射次数的影响

目的：探索抗血管内皮生长因子(VEGF)治疗的渗出性年龄相关性黄斑变性(nARMD)患眼中出现外层视网膜管型(ORT)的比例,及ORT出现前后抗VEGF治疗的频率。

方法：回顾性分析,共纳入按3+PRN方案治疗的nARMD患者54例60眼,基线时患者进行荧光素眼底血管造影(FFA)、眼底彩照(CFP)、最佳矫正视力(BCVA)及黄斑相干光断层扫描成像(OCT)检查,以后每月随访查BCVA、眼底彩照及黄斑OCT。记录患者OCT上视网膜下高反射物质(SHRM)的比例及随访中出现ORT结构的时间及比例,比较出现ORT前后玻璃体腔注射的平均次数。比较出现ORT眼及未出现ORT眼两组的BCVA及中心视网膜厚度(CRT)。

结果：在基线及随访至6、12、24mo时,ORT出现的比例分别为15.0%、21.7%、25.0%及46.7%。出现ORT后抗VEGF每月平均注射次数减少(P<0.05)。基线时有78.3%患眼出现SHRM,其中66.0%最后出现ORT,而在基线时不存在SHRM的13眼中仅23.1%眼出现ORT,相对风险值为2.86(P<0.01)。出现ORT眼较未出现ORT眼的BCVA更差及CRT更厚。

结论：ORT随着病程延长逐渐增加,ORT出现后抗VEGF再治疗的频率下降。     

抗VEGF与激光治疗1型早产儿视网膜病变的Meta分析

目的:系统评价抗VEGF与激光治疗1型早产儿视网膜病变(ROP)的疗效分析。方法:通过计算机检索PubMed、EMbase、CBM、The Cochrane Library、WanFang Data、CNKI和VIP数据库,收集比较抗VEGF与激光用于治疗1型ROP疗效的随机对照试验(RCT),检索时限均从建库至2020-01-06,按照纳入与排除标准提取资料,行质量评价后,采用RevMan 5.3软件进行Meta分析。结果:共纳入6个RCT。Meta分析结果显示:抗VEGF与激光组相比,复发率无差异[RR=0.94,95%CI(0.17~5.23),P=0.94];亚组分析Ⅰ区有差异[RR=0.17,95%CI(0.05~0.62),P=0.007];Ⅱ区无差异[RR=2.20,95%CI(0.07~73.48),P=0.66]。与激光组相比,再治疗率无差异[RR=2.36,95%CI(0.70~7.99),P=0.17],亚组分析Ⅰ区无差异[RR=0.33,95%CI(0.01~7.50),P=0.49];Ⅱ区有差异[RR=13,95%CI(1.84~92.01),P=0.01]。两者不良反应发生率无差异[RR=0.87,95%CI(0.54~1.40),P=0.57]。结论:激光和抗VEGF疗效相当,但在降低Ⅰ区复发率方面抗VEGF则更有优势,降低Ⅱ区再治疗率方面激光更有优势。     

Pediatric Inflammatory CNV: A Case Series from a Tertiary Referral Centre

ABSTRACT

Purpose: To report a case series of pediatric inflammatory choroidal neovascularization (CNV) seen at referral uveitis clinic.

Methods: Records of pediatric patients with uveitis and inflammatory CNV between January 2000 and December 2012 were analyzed.

Results: Ten eyes of seven patients were included. Mean age 12.6 years, mean follow-up 89.6 months. Three out of seven patients had bilateral CNV. Subfoveal CNV was noted in five eyes, extrafoveal CNV in three eyes and juxtafoveal and peripapillary CNV each in one eye. All patients received corticosteroids; immunosuppressives were used in three patients. Additional anti-VEGF injections were given, in six eyes, anti-VEGF and PDT in one eye and only PDT in three eyes.

Conclusion: Pediatric inflammatory CNV though challenging, can be successfully managed with prompt therapy of the underlying uveitic disease, coupled with additional local therapy to selectively target the CNV.     

首次抗VEGF早期应答对视网膜分支静脉阻塞继发黄斑水肿治疗的预测作用

目的：明确视网膜分支静脉阻塞（BRVO）导致黄斑水肿的患者首次抗血管内皮生长因子（VEGF）治疗24 h后黄斑区视网膜厚度的变化是否与治疗应答相关，并分析可以预测患者长期治疗效果的阈值。方法：回顾性系列病例研究。收集2014年12月至2016年12月于哈尔滨医科大学附属第二医院眼科门诊明确诊断为BRVO且采用0.5 mg雷珠单抗玻璃体腔首次注射+PRN治疗方案的患者276例。记录注射前，注射后24 h、4～48周（每4周1次）视网膜水肿情况（光学相干断层扫描），各观察时间点最佳矫正视力（BCVA，ETDRS视力表），通过受试者工作特征（ROC）曲线确定预测48周能否治愈的阈值，采用Pearson相关性分析及多因素Logistic回归分析确定影响治疗效果的因素。结果：所有符合条件的60例BRVO患者（60眼）在注射后各时间点中央黄斑厚度（CMT）均有显著下降，BCVA明显提高。首次注射后24 h CMT下降值与48周CMT下降值显著相关（r=0.664，P<0.001），与48周时视力变化显著相关（r=0.642，P<0.001）。ROC曲线分析显示，24 h CMT下降达18%对预后判断最具敏感性及特异性，按此阈值将入组患者分为2组：A组为CMT在24 h下降小于18%（24例）；B组为下降超过 18%（36例）。Logistic回归分析分组（<18%）是治愈的预测因子（OR：19.549，95%CI：4.324～88.378， P<0.01），48周内视力提高分别为（13±11）字母、（19±14）字母，2组差异有统计学意义（t=-1.375， P<0.001）。结论：BRVO导致黄斑水肿患者的抗VEGF长期治疗效果与早期视网膜厚度变化相关，首次治疗后24 h CMT下降幅度超过18%者长期治疗效果好。