Swept-Source OCT Angiographic Characteristics of Treatment-Naïve Nonexudative Macular Neovascularization in AMD Prior to Exudation

PurposeTo investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography.MethodsMNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs).ResultsTwenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements.ConclusionsThe onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.     

Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities

Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy. Meanwhile, the problem of suboptimal vision recovery (SVR) is defined as a failure to achieve excellent functional visual acuity of 20/40 or better in spite of sufficient anti-VEGF treatment. Thus, incomplete response to anti-VEGF therapy, and specifically PDA and SVR, represent significant clinical unmet needs.In this review, we will explore PDA and SVR in NVAMD, characterizing the clinical manifestations and exploring the pathobiology of each. We will demonstrate that PDA occurs most frequently in NVAMD patients who develop high-flow CNV lesions with arteriolarization, in contrast to patients with capillary CNV who are highly responsive to anti-VEGF therapy. We will review investigations of experimental CNV and demonstrate that both types of CNV can be modeled in mice. We will present and consider a provocative hypothesis: formation of arteriolar CNV occurs via a distinct pathobiology, termed neovascular remodeling (NVR), wherein blood-derived macrophages infiltrate the incipient CNV lesion, recruit bone marrow-derived mesenchymal precursor cells (MPCs) from the circulation, and activate MPCs to become vascular smooth muscle cells (VSMCs) and myofibroblasts, driving the development of high-flow CNV with arteriolarization and perivascular fibrosis. In considering SVR, we will discuss the concept that limited or poor vision in spite of anti-VEGF may not be caused simply by photoreceptor degeneration but instead may be associated with photoreceptor synaptic dysfunction in the neurosensory retina overlying CNV, triggered by infiltrating blood-derived macrophages and mediated by Müller cell activation Finally, for each of PDA and SVR, we will discuss current approaches to disease management and treatment and consider novel avenues for potential future therapies.     

光学相干断层扫描血管成像在糖尿病性视网膜病变临床应用研究进展

光学相干断层扫描血管成像(optical coherence tomography angiography, OCTA)作为一项近年来兴起的新型成像技术,具有非侵入性、快速、高分辨率等特点。相比于传统的造影检查,OCTA更加快速、安全且避免了传统造影剂带来的副作用和风险。如今OCTA已经逐渐应用于眼科疾病的诊疗与随访。通过对视网膜脉络膜血管的实时成像,可以用于观察疾病如糖尿病视网膜病变、脉络膜新生血管等的进展。本文就OCTA在糖尿病视网膜病变的临床应用研究进展进行综述。     

康柏西普治疗慢性中心性浆液性脉络膜视网膜病变继发脉络膜新生血管的疗效及安全性

目的观察康柏西普玻璃体腔注射治疗慢性中心性浆液性脉络膜视网膜病变继发脉络膜新生血管(CSC-CNV)的疗效和安全性。方法采用回顾性病例观察研究,收集2015年9月至2018年1月在温州医科大学附属眼视光医院杭州院区确诊为慢性CSC-CNV的13例14眼患者病例资料,所有患眼均接受玻璃体腔注射0.05 ml/0.5 mg康柏西普治疗,采用1+按需治疗(PRN)方案,观察注射前及注射后1周、1个月、2个月、3个月、6个月时最佳矫正视力(BCVA)、黄斑中心凹视网膜厚度(CMT)变化。结果6个月随访期内,患眼平均注射次数为(1.93±0.83)次,所有CSC继发的CNV均未突破视网膜色素上皮层。患者玻璃体腔注射前,首次注射后1周、1个月、2个月、3个月和6个月时BCVA分别为0.51±0.32、0.43±0.34、0.36±0.35、0.31±0.28、0.27±0.29和0.26±0.30,CMT值分别为(299.07±132.90)、(216.50±70.94)、(203.00±61.87)、(234.29±95.70)、(194.21±46.46)和(207.43±55.46)μm,总体比较差异均有统计学意义(F=21.225、3.768,均P<0.05);注射后各时间点BCVA均明显优于注射前,CMT值均明显低于注射前,差异均有统计学意义(均P<0.05)。治疗随访期间未出现与治疗相关的严重并发症。结论慢性CSC-CNV患者玻璃体腔注射康柏西普可在短期内降低CMT、提高BCVA,安全性较好。     

Effects of quercetin on diabetic retinopathy and its association with NLRP3 inflammasome and autophagy

AIM: To investigate the effects of quercetin on diabetic retinopathy (DR) and its association with nucleotide-binding oligomerization domain-like receptors 3 (NLRP3) inflammasome and autophagy using retinal endothelial cell as an experimental model. METHODS: Human retinal microvascular endothelial cells (HRMECs) were cultured in vitro and assigned into the control group, high-glucose (HG) group, and HG+different concentrations of quercetin groups. Cellular viability, migration, and tube formation in these groups was detected by MTT, transwell and matrigel assay, respectively. Expressions of NLRP3, apoptosis-associated speck-like protein (ASC), cysteiny aspartate-specific protease-1 (Caspase-1) as well as microtubule-related protein 1 light chain 3 (LC3) and Beclin-1 were detected by Western blotting. Expressions of IL-1β and IL-18 were detected by ELISA and cellular autophagy was detected by Cyto-ID® autophagy detection kit. RESULTS: Under an HG condition, the viability, migration, tube formation of HRMECs, and the protein expressions of NLRP3, ASC, Caspase-1, IL-1β, IL-18, LC3, and Beclin-1 as well as autophagy were all increased. Quercetin inhibited angiogenesis of HRMECs as well as the expressions of NLRP3, ASC, Caspase-1, IL-1β, IL-18, LC3, Beclin-1, and autophagy of HRMECs under a HG condition. The inhibitory effects of quercetin on angiogenesis, NLRP3 inflammasome and autophagy increased with the increase of its concentration. CONCLUSION: The therapeutic potential of quercetin in retinal neovascularization of DR, and inhibition of NLRP3 inflammasome and autophagy signaling pathway may be involved.     

光动力疗法治疗病理性近视脉络膜新生血管的临床观察

目的 探讨病理性近视脉络膜新生血管采用光动力疗法（PDT）治疗的临床效果.方法 选择病理性近视脉络膜新生血管患者20例（20眼）,均采用PDT治疗,回顾性分析治疗前后临床资料.结果 末次随访时,检测视力呈＞2行提高者3眼,占15％;保持稳定者16眼,占80％;视力下降1眼,占5％.眼底检查示视网膜神经感觉层缩小或脱离,黄斑渗出、水肿、出血均有程度不等的吸收.视网膜出血在治疗6个月后基本吸收.眼底荧光血管造影（FFA）/吲哚青绿血管造影（ICGA）在治疗后3个月检查显示,12只眼黄斑下脉络膜新生血管（CNV）荧光素渗漏静止,CNV闭合占60％,9只眼CNV渗漏好转,占45％.结论 CNV采用PDT治疗可获得理想效果,因为短期观察,选取的病例数相对较少,而从根本上,PDT无法杜绝CNV发生,故存在未彻底治疗的情况,长时间不能完全消失,也不能改善远期视力,若需客观评价PDT疗法,需行远期观察.     

VEGF基因RNA干扰质粒的构建与鉴定

目的构建干扰血管内皮生长因子（vascular endothelial growth factor,VEGF）基因RNA表达的重组质粒。方法设计3组针对VEGF基因的核糖核酸干扰（RNA interference,RNAi）序列,应用基因重组技术克隆入载体pcDNA3.1中,重组质粒分别命名为pcDNA3.1-VEGF-LH1、pcDNA3.1-VEGF-LH2和pcDNA3.1-VEGF-LH3,用DNA直接测序法和双酶切法鉴定构建的重组质粒。结果 DNA测序证实克隆入载体pcDNA3.1（-）中的序列正确,双酶切证实RNA干扰序列正确插入载体pcDNA3.1（-）。结论成功构建针对VEGF基因的RNAi质粒,为进一步研究该RNAi质粒在脉络膜新生血管形成中的作用奠定了基础。     

地塞米松抑制视网膜新生血管及血管内皮生长因子表达的实验研究

目的:研究地塞米松(Dexamethasone)在小鼠血管增生性视网膜病变中不同时期的给药效果,及其与血管内皮生长因子(VEGF)的相互作用。方法:将20只7 d龄C57BL/6J幼鼠随机分为4组:正常对照组、模型组、早治疗组和晚治疗组。除对照组外,均建立高浓度氧气诱导的C57BL/6J幼鼠增殖性视网膜病变模型。后2组分别于出生后第7d和第12d起连续5d皮下注射地塞米松注射液(0.5mg/kg.d-1)。17d龄时取幼鼠双眼球作普通病理切片及免疫组化检测,分别检测视网膜新生血管芽内皮细胞核数目及VEGF的表达。结果:模型组视网膜新生血管芽内皮细胞核数目及VEGF的表达较正常对照组明显增加(P<0.01);早治疗组与晚治疗组的视网膜新生血管芽内皮细胞核数目和VEGF表达,较模型组均明显减少(P<0.01);早治疗组较晚治疗组也明显减少(P<0.01)。结论:在氧诱导的血管增生性视网膜病变模型中,地塞米松可以抑制视网膜新血管形成和VEGF的表达,而且病变早期应用地塞米松治疗效果明显优于晚期。     

Expression profiles of long noncoding RNAs in retinopathy of prematurity

Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic retinopathy.Based on similarities between the pathogenesis of retinopathy of prematurity(ROP)and diabetic retinopathy,lncRNA may also play a role in ROP.Seven-day-old mice were administered 75±2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model.Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology,and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The results showed that compared with the control group,57 lncRNAs were differentially expressed,including 43 upregulated and 14 downregulated,in the retinal tissue of ROP mice.Compared with control mice,42 mRNAs were differentially expressed in the retinal tissue of ROP mice,including 24 upregulated and 18 downregulated mRNAs.Differentially expressed genes were involved in ocular development and related metabolic pathways.The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways.Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment.This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25,2016(approval No.2016PS074K).