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Screening and treatments using telemedicine in retinopathy of prematurity. 早产儿视网膜病变的远程医疗筛查与治疗。
IF 4.4 Q1 Medicine Pub Date : 2016-08-17 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S94440
Aristomenis Thanos, Yoshihiro Yonekawa, Bozho Todorich, Darius M Moshfeghi, Michael T Trese

Several studies have validated the role of telemedicine as a new powerful screening and diagnostic tool for retinal disorders, such as diabetic retinopathy and retinopathy of prematurity. With regard to retinopathy of prematurity, bedside examination with binocular indirect ophthalmoscopy has been the gold standard technique for screening, yet with several limitations. Herein, we review the current evidence that supports the role of telemedicine for the screening of infants with retinopathy of prematurity.

一些研究已经证实了远程医疗作为一种新的强大的筛查和诊断视网膜疾病的工具的作用,如糖尿病视网膜病变和早产儿视网膜病变。关于早产儿视网膜病变,双眼间接检眼镜床边检查一直是筛查的金标准技术,但仍有一些局限性。在此,我们回顾了目前支持远程医疗在早产儿视网膜病变筛查中的作用的证据。
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引用次数: 10
Wnt signaling pathway in retinal vascularization. 视网膜血管化中的Wnt信号通路。
IF 4.4 Q1 Medicine Pub Date : 2016-08-09 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S94452
Kimberly A Drenser

Wnt-signaling, a ubiquitous pathway that directs differentiation, cell polarity, and tissue specificity, has been implicated as an important gene-expression pathway in retinal development. An increasing body of evidence supports the importance of Wnt-signaling, and specifically, norrin-mediated Wnt-signaling in retinal development and retinal maintenance. Gene mutations affecting the Wnt-signaling pathways result in a variety of inherited vitreoretinopathies. Additionally, there is growing evidence that prematurity and associated retinopathy are associated with alterations in the Wnt-signaling pathways. Further investigations may allow for improved diagnoses, management, and therapies in the future.

wnt信号是一种普遍存在的指导分化、细胞极性和组织特异性的途径,已被认为是视网膜发育中重要的基因表达途径。越来越多的证据支持wnt信号,特别是调节蛋白介导的wnt信号在视网膜发育和视网膜维持中的重要性。影响wnt信号通路的基因突变导致多种遗传性玻璃体视网膜病变。此外,越来越多的证据表明,早产和相关的视网膜病变与wnt信号通路的改变有关。进一步的调查可能会在未来改善诊断、管理和治疗。
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引用次数: 33
Review of effects of anti-VEGF treatment on refractive error. 抗vegf治疗屈光不正的研究进展。
IF 4.4 Q1 Medicine Pub Date : 2016-06-15 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S99306
Helen A Mintz-Hittner, Megan M Geloneck

To examine the effect of anti-vascular endothelial growth factor (anti-VEGF) agents on refractive error in the setting of retinopathy of prematurity (ROP) through a review of the literature, a PubMed search was performed of appropriate search terms, and the results of all relevant studies were extracted and compiled. Eleven relevant articles were identified in the literature, totaling 466 eyes, treated with varied anti-VEGF agents (bevacizumab, ranibizumab, and aflibercept) with mean spherical equivalent refractions ranging from +0.75 D to -3.57 D, with prevalence of high myopia ranging from 0 to 35%. Anti-VEGF monotherapy for ROP leads to low levels of myopia, and there may be a differential effect of specific anti-VEGF agents utilized on refractive outcomes.

通过文献综述,探讨抗血管内皮生长因子(anti-VEGF)药物对早产儿视网膜病变(ROP)屈光不正的影响,在PubMed上检索合适的检索词,提取并汇总所有相关研究的结果。在文献中鉴定出11篇相关文章,共466只眼,使用各种抗vegf药物(贝伐单抗、雷尼单抗和阿非利赛普)治疗,平均球面等效屈光度在+0.75 D至-3.57 D之间,高度近视患病率在0 - 35%之间。抗vegf单药治疗ROP可导致低度数近视,使用特定的抗vegf药物对屈光结果可能有不同的影响。
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引用次数: 28
Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development. 早产儿眼的光学相干断层扫描:从早产儿视网膜病变到大脑发育。
IF 4.4 Q1 Medicine Pub Date : 2016-05-27 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S97660
Adam L Rothman, Shwetha Mangalesh, Xi Chen, Cynthia A Toth

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment.

患有早产儿视网膜病变的早产儿神经发育不良的风险增加。由于神经感觉视网膜是中枢神经系统的延伸,前视通路的解剖异常通常与系统和中枢神经系统健康有关。我们将光学相干断层扫描描述为一种强大的成像方式,最近已适应于婴儿人群,并提供床边婴儿眼睛的无创,高分辨率,横断面成像。光学相干断层扫描增加了对正常眼睛发育的理解,并确定了大脑异常和较差神经发育的几个潜在生物标志物。
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引用次数: 15
Promoting vascular repair in the retina: can stem/progenitor cells help? 促进视网膜血管修复:干细胞/祖细胞有帮助吗?
IF 4.4 Q1 Medicine Pub Date : 2016-05-26 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S94451
Thao Le Phuong Trinh, Sergio Li Calzi, Lynn C Shaw, Mervin C Yoder, Maria B Grant

Since its first epidemic in the 1940s, retinopathy of prematurity (ROP) has been a challenging illness in neonatology. Higher than physiological oxygen levels impede the development of the immature retinal neuropil and vasculature. Current treatment regimens include cryotherapy, laser photocoagulation, and anti-VEGF agents. Unfortunately, none of these approaches can rescue the normal retinal vasculature, and each has significant safety concerns. The limitations of these approaches have led to new efforts to understand the pathological characteristics in each phase of ROP and to find a safer and more effective therapeutic approach. In the era of stem cell biology and with the need for new treatments for ROP, this review discusses the possible future use of unique populations of proangiogenic cells for therapeutic revascularization of the preterm retina.

自20世纪40年代首次流行以来,早产儿视网膜病变(ROP)一直是新生儿学中一种具有挑战性的疾病。高于生理氧水平阻碍未成熟视网膜神经和血管系统的发育。目前的治疗方案包括冷冻疗法、激光光凝和抗vegf药物。不幸的是,这些方法都不能挽救正常的视网膜血管系统,而且每一种方法都有重大的安全问题。这些方法的局限性导致了新的努力,以了解ROP的每个阶段的病理特征,并找到一个更安全,更有效的治疗方法。在干细胞生物学的时代,随着对ROP新治疗方法的需要,本综述讨论了未来可能使用独特的促血管生成细胞群用于治疗性早产儿视网膜血运重建。
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引用次数: 12
Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy. 抗vegf治疗早产儿视网膜病变:我们从氧诱导视网膜病变的代表性动物模型中学到的东西
IF 4.4 Q1 Medicine Pub Date : 2016-05-20 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S94449
Haibo Wang

Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness, affecting infants born prematurely. ROP is characterized by the onset of delayed physiological retinal vascular development (PRVD) and followed by pathologic neovascularization into the vitreous instead of the retina, called intravitreal neovascularization (IVNV). Therefore, the therapeutic strategy for treating ROP is to promote PRVD and inhibit or prevent IVNV. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of ROP. There is a growing body of studies testing the use of anti-VEGF agents as a treatment for ROP. Intravitreal anti-VEGF treatment for ROP has potential advantages compared with laser photocoagulation, the gold standard for the treatment of severe ROP; however, intravitreal anti-VEGF treatment has been associated with reactivation of ROP and suppression of systemic VEGF that may affect body growth and organ development in preterm infants. Therefore, it is important to understand the role of VEGF in PRVD and IVNV. This review includes the current knowledge of anti-VEGF treatment for ROP from animal models of oxygen-induced retinopathy (OIR), highlighting the importance of VEGF inhibition by targeting retinal Müller cells, which inhibits IVNV and permits PRVD. The signaling events involved in mediating VEGF expression and promoting VEGF-mediated angiogenesis, including hypoxia-dependent signaling, erythropoietin/erythropoietin receptor-, oxidative stress-, beta-adrenergic receptor-, integrin-, Notch/Delta-like ligand 4- and exon guidance molecules-mediated signaling pathways, are also discussed.

早产儿视网膜病变(ROP)仍然是儿童失明的主要原因,影响早产儿。ROP的特点是生理性视网膜血管发育(PRVD)延迟,随后病理性新生血管进入玻璃体而不是视网膜,称为玻璃体内新生血管(IVNV)。因此,治疗ROP的治疗策略是促进PRVD,抑制或预防IVNV。血管内皮生长因子(VEGF)在ROP的发病机制中起重要作用。越来越多的研究测试使用抗vegf药物治疗ROP。玻璃体内抗vegf治疗ROP与治疗重度ROP的金标准激光光凝相比具有潜在优势;然而,玻璃体内抗VEGF治疗与ROP的再激活和全身VEGF的抑制有关,这可能影响早产儿的身体生长和器官发育。因此,了解VEGF在PRVD和IVNV中的作用非常重要。本文综述了氧诱导视网膜病变(OIR)动物模型中抗VEGF治疗ROP的现有知识,强调了通过靶向视网膜膜层细胞抑制VEGF的重要性,这可以抑制IVNV并允许PRVD。还讨论了介导VEGF表达和促进VEGF介导的血管生成的信号通路,包括缺氧依赖性信号通路、促红细胞生成素/促红细胞生成素受体-、氧化应激-、β -肾上腺素能受体-、整合素-、Notch/ δ样配体4-和外显子引导分子介导的信号通路。
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引用次数: 21
Retinal, visual, and refractive development in retinopathy of prematurity. 早产儿视网膜病变的视网膜、视觉和屈光发育。
IF 4.4 Q1 Medicine Pub Date : 2016-05-20 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S95021
Anne Moskowitz, Ronald M Hansen, Anne B Fulton

The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria. On the other hand, deficits in post-receptor sensitivity are present in infancy regardless of the severity of the ROP but are not present in older children if the ROP was so mild that it never required treatment and resolved without a clinical trace. Accompanying the persistent deficits in photoreceptor sensitivity, there is increased receptive field size and thickening of the post-receptor retinal laminae in the peripheral retina of ROP subjects. In the late maturing central retina, which mediates visual acuity, attenuation of multifocal electroretinogram activity in the post-receptor retina led us to the discovery of a shallow foveal pit and significant thickening of the post-receptor retinal laminae in the macular region; this is most likely due to failure of the normal centrifugal movement of the post-receptor cells during foveal development. As for refractive development, myopia, at times high, is more common in ROP subjects than in control subjects, in accord with refractive findings in other populations of former preterms. This information about the neurosensory retina enhances understanding of vision in patients with a history of ROP, and taken as a whole, raises the possibility that the neurosensory retina is a target for therapeutic intervention.

神经感觉视网膜在早产儿视网膜病变(ROP)疾病过程中的关键作用已在大鼠模型中得到充分证明。我们推测人类早产儿视网膜病变也有类似的细胞过程,并通过对婴儿和儿童的感光器和后感光器外周和中央视网膜进行一系列非侵入性研究,对这些推测进行了评估。研究的主要结果是,根据临床标准,光传导动力学减慢和感光器敏感性缺损在视网膜病变完全缓解多年后仍然存在。另一方面,无论视网膜病变的严重程度如何,婴儿期都会出现感光受体后敏感性缺损,但如果视网膜病变的程度很轻,无需治疗,而且在没有临床症状的情况下就会消失,那么年龄较大的儿童就不会出现这种缺损。伴随着感光器灵敏度的持续缺陷,ROP 受试者周边视网膜的感受野增大,感受器后视网膜板层增厚。在晚期成熟的中央视网膜中,受体后视网膜的多灶视网膜电图活动衰减,导致我们发现眼窝凹陷较浅,黄斑区的受体后视网膜板层明显增厚;这很可能是由于受体后细胞在眼窝发育过程中无法正常离心运动所致。在屈光发育方面,与对照组相比,ROP 患者更常见近视,有时甚至是高度近视,这与其他早产儿人群的屈光结果一致。这些关于神经感觉视网膜的信息加深了人们对有早产儿视网膜病史的患者视力的了解,从整体上看,神经感觉视网膜有可能成为治疗干预的目标。
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引用次数: 0
Impact of improved neonatal care on the profile of retinopathy of prematurity in rural neonatal centers in India over a 4-year period. 改善新生儿护理对印度农村新生儿中心4年早产儿视网膜病变概况的影响。
IF 4.4 Q1 Medicine Pub Date : 2016-05-20 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S98715
Anand Vinekar, Chaitra Jayadev, Siddesh Kumar, Shwetha Mangalesh, Mangat Ram Dogra, Noel J Bauer, Bhujang Shetty

Purpose: To report the reduction in the incidence and severity of retinopathy of prematurity (ROP) in rural India over a 4-year period following the introduction of improved neonatal care practices.

Methods: The Karnataka Internet Diagnosis of Retinopathy of Prematurity program (KIDROP), is a tele-medicine network that screens for ROP in different zones of Karnataka state in rural India. North Karnataka is the most underdeveloped and remote zone of this program and did not have any ROP screening programs before the intervention of the KIDROP in 2011. Six government and eleven private neonatal centers in this zone were screened weekly. Specific neonatal guidelines for ROP were developed and introduced in these centers. They included awareness about risk factors, oxygen regulation protocols, use of pulse oxymetry, monitoring postnatal weight gain, nutritional best practices, and management of sepsis. The incidence and severity of ROP were compared before the guidelines were introduced (Jan 2011 to Dec 2012) and after the guidelines were introduced (July 2013 to June 2015).

Results: During this 4-year period, 4,167 infants were screened over 11,390 imaging sessions. The number of enrolled infants increased from 1,825 to 2,342 between the two periods (P<0.001). The overall incidence of any stage ROP reduced significantly from 26.8% to 22.4% (P<0.001). The incidence of treatment-requiring ROP reduced from 20.7% to 16% (P=0.06), and of the treated disease, aggressive posterior ROP reduced from 20.8% to 13.1% (P=0.23) following introduction of the guidelines.

Discussion: Rural neonatal centers in middle-income countries have a large, unscreened burden of ROP. Improving neonatal care in these centers can positively impact the incidence and severity of ROP even in a relatively short period. A combined approach of a robust ROP screening program and improved neonatal care practices is required to address the challenge.

目的:报告印度农村早产儿视网膜病变(ROP)的发病率和严重程度在引进改进的新生儿护理实践后的4年期间的降低。方法:卡纳塔克邦互联网早产儿视网膜病变诊断项目(KIDROP)是一个远程医疗网络,在印度农村卡纳塔克邦的不同地区筛查视网膜病变。北卡纳塔克邦是该项目最不发达和偏远的地区,在2011年KIDROP干预之前没有任何ROP筛查项目。该地区的6个政府和11个私人新生儿中心每周进行筛查。这些中心制定并介绍了新生儿ROP的具体指南。其中包括对危险因素的认识、氧气调节方案、脉搏血氧仪的使用、产后体重增加的监测、营养最佳做法和败血症的管理。比较指南实施前(2011年1月至2012年12月)和实施后(2013年7月至2015年6月)ROP的发生率和严重程度。结果:在这4年期间,4167名婴儿接受了11,390次影像学检查。在这两个时期,入组婴儿的数量从1825名增加到2342名(PPP=0.06),在接受治疗的疾病中,引入指南后,侵袭性后路ROP从20.8%减少到13.1% (P=0.23)。讨论:中等收入国家的农村新生儿中心存在大量未经筛查的ROP负担。在这些中心改善新生儿护理可以积极影响ROP的发生率和严重程度,即使在相对较短的时间内。需要一个强有力的ROP筛查项目和改进的新生儿护理实践相结合的方法来应对这一挑战。
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引用次数: 21
Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity. 靶向VEGF治疗犬氧诱导视网膜病变-人早产儿视网膜病变模型。
IF 4.4 Q1 Medicine Pub Date : 2016-05-20 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S94443
D Scott McLeod, Gerard A Lutty

Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.

犬视网膜浅表血管的发育机制与人类视网膜血管的发育机制相似;它们都是通过血管发生、分化和血管前体(称为成血管细胞)的组装而形成的。犬氧诱导视网膜病变(OIR)是由Arnall Patz首先提出的,目的是通过实验确定高氧对视网膜血管系统发育的影响。犬类视网膜病变与人类早产儿视网膜病变有许多共同的特点。1天大的狗暴露于高氧环境4天会导致整个视网膜血管闭塞。在动物回到室内空气后,血管增生非常强劲。最初的小视网膜前新生血管相互吻合形成大的视网膜前膜,最终引起牵拉性视网膜褶皱。犬模型的终末期病理与人类早产儿视网膜病变IV期相似。因此,犬OIR是评估针对VEGF及其受体的药物反应的一个很好的论坛。对VEGF- r2抗体和VEGF- trap的评估表明,剂量应该降低,以抑制视网膜前的新血管形成,但视网膜的血管重建能够进行,使周围视网膜血管化,并防止其成为VEGF的来源。
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引用次数: 9
Retinopathy of prematurity: the need for prevention. 早产儿视网膜病变:需要预防。
IF 4.4 Q1 Medicine Pub Date : 2016-05-20 eCollection Date: 2016-01-01 DOI: 10.2147/EB.S99038
Raffael Liegl, Ann Hellström, Lois Eh Smith

More than 450,000 babies are born prematurely in the USA every year. The improved survival of even the most vulnerable low body weight preterm infants has, despite improving health outcomes, led to the resurgence in preterm complications including one of the major causes for blindness in children, retinopathy of prematurity (ROP). The current mainstay in ROP therapy is laser photocoagulation and the injection of vascular endothelial growth factor (VEGF) antibodies in the late stages of the disease after the onset of neovascularization. Both are proven options for ophthalmologists to treat the severe forms of late ROP. However, laser photocoagulation destroys major parts of the retina, and the injection of VEGF antibodies, although rather simple to administer, may cause a systemic suppression of normal vascularization, which has not been studied in sufficient depth. However, the use of neither VEGF antibody nor laser treatment prevents ROP, which should be the long-term goal. It should be possible to prevent ROP by more closely mimicking the intrauterine environment after preterm birth. Such preventive measures include preventing the toxic postbirth influences (eg, oxygen excess) as well as providing the missing intrauterine factors (eg, insulin growth factor 1) and are likely to also reduce other complications of premature birth as well as ROP. This review is meant to summarize the current knowledge on the prevention of ROP with a particular emphasize on the use of insulin growth factor 1 supplementation.

在美国,每年有超过45万婴儿早产。即使是最脆弱的低体重早产儿存活率的提高,尽管改善了健康结果,但导致早产并发症的重新出现,包括导致儿童失明的主要原因之一,早产儿视网膜病变。目前主要的ROP治疗方法是激光光凝和在疾病晚期新血管形成后注射血管内皮生长因子(VEGF)抗体。这两种方法都是眼科医生治疗晚期严重ROP的有效方法。然而,激光光凝会破坏视网膜的主要部分,而注射VEGF抗体虽然操作简单,但可能导致正常血管形成的全身抑制,这方面的研究还不够深入。然而,无论是使用VEGF抗体还是激光治疗都不能预防ROP,这应该是长期的目标。通过更密切地模仿早产后的宫内环境,应该可以预防ROP。这些预防措施包括预防产后毒性影响(例如,氧气过量)以及提供缺失的宫内因子(例如,胰岛素生长因子1),并可能减少早产的其他并发症以及ROP。本综述旨在总结目前关于预防ROP的知识,特别强调补充胰岛素生长因子1的使用。
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引用次数: 36
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