Serum vascular endothelial growth factor,insulin-like growth factor-1 and aflibercept levels in retinopathy of prematurity

Japanese Journal of Ophthalmology - To evaluate the serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) after intravitreal injection of aflibercept...     

血管内皮生长因子在早产儿视网膜病变中的作用研究进展

视网膜新生血管形成是眼部多种疾病共有的病理特点,其引发的疾病已成为目前致盲的重要原因.VEGF家族在新生血管形成中扮演着重要的角色,其通过影响细胞增生、细胞迁移、诱导毛细血管腔形成,从而促进新生血管的生成和生长.本文以早产儿视网膜病变为例,介绍VEGF家族及其受体,在早产儿视网膜病变的病理过程中的作用和针对其作用机制可采取的相应防治方法.     

血管内皮生长因子基因多态性与早产儿视网膜病变发病和预后的关系

背景不同早产儿个体之间对早产儿视网膜病变（ROP）发病易感性的差异较大,可能与血管内皮生长因子（VEGF）基因多态性有关。目的研究ROP患儿VEGF基因多态性的表型,探讨VEGF基因多态性与ROP的关系。方法采用前瞻性系列病例对照研究设计,纳入2006年1月至2009年12月在湖南省儿童医院新生儿科住院的1～5期ROP患儿99例作为ROP组,另纳入80例同期未发生ROP的早产儿为对照无ROP组;在ROP组中将行激光或冷冻治疗的患儿39例作为治疗组,同期未经治疗ROP自发消退的患儿60例作为非治疗组。ROP组与无ROP组间、治疗组与非治疗组问的人口基线学特征比较差异均无统计学意义（P〉0．05）。抽取各组患儿外周血2ml以提取DNA,利用焦磷酸测序法进行VEGF—A＋405、VEGF—A936基因的多态性研究。结果ROP组患儿与无ROP组患儿VEGF—A＋405基因表型的差异均无统计学意义（P=0．071,OR=0．675,95％c,=0．444～1．026）。ROP组患儿与无ROP组患儿VEGF—A936基因表型的差异亦无统计学意义（P=0．118,OR=0．768,95％CI为2．823～4．614）,但治疗组与非治疗组VEGF—A＋405,VEGF—A936基因多态性表型的差异均有统计学意义（VEGF—A＋405：P〈0．01,OR=0．875,95％C1为5．239～14．024;VEGF—A936：P=0．000,OR=3．609,95％CI为0．711～0．829）。结论VEGF—A＋405和VEGF—A936基因的多态性与ROP易感性无关,但与ROP预后有关。携带VEGF—A＋405、VEGF—A936等位基因可能增加ROP进展的风险。     

Genetic polymorphisms of vascular endothelial growth factor and angiopoietin 2 in retinopathy of prematurity

Angiogenic factors such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) contribute to development of retinopathy of prematurity (ROP). We aimed to test whether polymorphisms of these factors are associated with ROP. VEGF(-2578) and Ang2(-35) polymorphisms were analyzed with PCR-RFLP method in 200 preterm infants without ROP or with ROP stages 1-5. Our results suggest that there is no association between carrier state of VEGF(-2578) and Ang2(-35) and risk of ROP in preterm infants. The prevalence of VEGF(-2578) "A" allele was lower in preterm boys with severe ROP (stages 4-5) than in those without or with mild ROP (stages 1-3).     

Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity.

OBJECTIVES: We had the unique opportunity to compare the eyes of a premature infant with stage 3 retinopathy of prematurity (ROP) in both eyes after the condition was treated by diode laser photocoagulation in one eye only. After the infant's death, we investigated the extent of structural damage incurred with the diode laser and examined the effect of treatment on vascular endothelial growth factor (VEGF) expression. METHODS: The eyes were fixed and embedded in paraffin. Adjacent 6 microns sections were either stained for histopathologic analysis or used for in situ hybridization. VEGF messenger RNA (mRNA) was detected by using radiolabeled antisense riboprobes. RESULTS: In the treated eye, histopathologic results demonstrated the clinically evident dose-response effect, with sparing of inner retinal elements with mild laser burns and full-thickness retinal cell disruption with severe burns. Scleral and ciliary nerve effects were absent. VEGF mRNA was localized primarily in the ganglion cell layer but was also found in the inner nuclear layer. In the untreated eye, an increase in VEGF mRNA was detected at the peripheral edge of the vascularized retina anterior to the ridge. In the laser-treated eye, VEGF mRNA expression was dramatically upregulated in the ganglion cell layer in areas adjacent to laser burns. CONCLUSIONS: VEGF mRNA was found to be elevated in the peripheral, avascular retina of the untreated eye, consistent with the hypothesis that retinal hypoxia stimulates VEGF expression. In the treated eye with recurrent ROP, VEGF mRNA was not detected in the photocoagulated areas of retina but was increased between laser scars. This finding confirms the results of prior animal studies and validates the use of these models.     

Aqueous vascular endothelial growth factor and ranibizumab concentrations after monthly and bimonthly intravitreal injections of ranibizumab for age-related macular degeneration

Purpose

To evaluate vascular endothelial growth factor (VEGF) and ranibizumab concentrations in eyes with age-related macular degeneration (AMD) after monthly and bimonthly intravitreal ranibizumab (IVR) injections.

Methods

Aqueous humor samples were obtained from 26 eyes with AMD before and after IVR injections. Nine eyes received three monthly injections and 17 eyes received two bimonthly injections. The VEGF and ranibizumab concentrations were measured by enzyme-linked immunosorbent assay.

Results

The aqueous VEGF concentrations in the monthly injection group decreased below the lowest detectable limit in eight of nine eyes 1 month after the first injection and seven of nine eyes 1 month after the second injection (P?<?0.001, mean baseline value, 94.7 pg/ml); the aqueous VEGF concentrations in the bimonthly injection group decreased below the lowest detectable limit in two of 17 eyes 2 months after the first injection (P?<?0.001, mean baseline value, 152.4 pg/ml). The mean aqueous ranibizumab concentrations with monthly injections were 71.2 ng/ml 1 month after the first injection, and 96.3 ng/ml 1 month after the second injection. The mean aqueous ranibizumab concentrations in the bimonthly injection group were 2.5 ng/ml in 15 of 17 eyes, and below the lowest detectable limit in two of 17 eyes 2 months after the first injection.

Conclusions

In this pilot study with limited follow-up, intravitreal injection of ranibizumab can suppress aqueous VEGF completely for 1 month in most cases. Its effect does not last for 2 months enough to suppress VEGF completely in most cases, although aqueous VEGF at 2 months after intravitreal injection of ranibizumab is less than that before injection in most cases.     

Repeated intravitreal ranibizumab for reactivated retinopathy of prematurity after intravitreal ranibizumab monotherapy: vascular development analysis

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the retinal vascularization of repeated intravitreal ranibizumab (IVR) for reactivated retinopathy of prematurity...     

早产儿视网膜病变抗血管内皮生长因子药物治疗新进展

早产儿视网膜病变（retinopathy of prematurity,ROP）是一种进行性视网膜血管异常生长、病理性新生血管形成的致盲性眼病。传统一线治疗激光光凝,存在治疗相对滞后、不可逆周边视野缺损等局限性。近年来,以哌加他尼钠、贝伐单抗、雷珠单抗、阿柏西普和康柏西普等为代表的抗血管内皮生长因子药物已广泛用于眼底新生血管性疾病,尤其在ROP治疗中不断取得新的进展,并成为其基础和临床研究的焦点和热点。     

血管内皮生长因子基因多态性与早产儿视网膜病变预后的相关性研究

目的 观察中国人早产儿视网膜病变(ROP)预后与血管内皮生长因 子（VEGF）基因多态性的相关性。方法 临床确诊为ROP阈值病变行视网膜激光光凝治 疗的ROP患儿20例作为观察组，未经治疗自发消退的ROP患儿20例作为对照组，两组患儿均有吸氧史，除出生体重外，性别、孕周等均匹配。应用聚合酶链反应限制性片段长度多态性分析（PCR-RFLP） 结合DNA测序检测VEGF基因的多态性。结果 观察组+405C等位基因的频率明显高于对照组（P＜0.05），而460T/C和+936C/T位点多态性在两组间的差异无统计学意义（P＞0.05）。结论 VEGF+405C/G基因多态性与ROP预后可能存在相关性，携带+405C等位基因可能增加ROP进展的风险性。     

Low-dose ranibizumab administration in retinopathy of prematurity

International Ophthalmology - To evaluate the efficiency of low-dose intravitreal ranibizumab therapy in the treatment of aggressive retinopathy of prematurity (A-ROP). A total of 124 eyes of 62...     

玻璃体内注射雷珠单抗治疗早产儿视网膜病变

目的　观察玻璃体内注射雷珠单抗治疗早产儿视网膜病变（ｒｅｔｉｎｏｐａｔｈｙｏｆｐｒｅｍａ-ｔｕｒｉｔｙ,ＲＯＰ）的疗效及其安全性。方法　回顾分析了２０１２年１１月至２０１４年５月于北京同仁医院治疗的１７例（３１眼）ＲＯＰ患儿,在４８ｈ内行玻璃体内注射雷珠单抗,对注射后无反应者,重复玻璃体内注射雷珠单抗或联合激光光凝治疗,术后１ｄ、１个月内每周随访观察复诊。结果　所有治疗眼中,单纯行玻璃体内注射雷珠单抗２７眼,玻璃体内注射雷珠单抗联合激光治疗４眼。２８眼进行了一次治疗,３眼经过了二次注射治疗;４眼进行补充视网膜激光治疗。所有的ＲＯＰ治疗均有效,随访期内未见有复发病例。结论　玻璃体内注射雷珠单抗对ＲＯＰ的治疗效果可靠,尤其对于病情严重、全身情况差不能耐受全身麻醉的患儿,其优势明显。