胰岛素样生长因子-1启动子区域CA重复序列多态性与早产儿视网膜病相关性研究

目的探讨胰岛素样生长因子-1（IGF-1）启动子区域CA重复序列多态性与早产儿视网膜病（ROP）的相关性。方法将2010年1月至2012年6月在广东省妇幼保健院新生儿科住院期间发生ROP病变的早产儿为病例组,按1∶1的比例选择同期住院追踪至眼底周边视网膜血管化无ROP病变的早产儿为对照组,抽取血液样本进行基因多态性分析。所有研究对象父母均为广东户籍。采用比值比（OR）和95%可信区间（CI）进行风险估计,采用Pearson相关进行直线相关分析。结果病例组和对照组各纳入56例早产儿,性别差异无统计学意义（P〉0.05）。在研究对象中共检测到7种重复序列,（CA）19重复序列最多,占41.1%。携带各种基因型与ROP的风险评估中,携带IGF-1（CA）17、19、21重复序列的OR（95%CI）分别是1.828（0.517-6.457）、1.210（0.678-2.160）、1.251（0.662-2.364）,P均〉0.05。携带各种基因型与ROP的直线相关分析rs值0.012,P〉0.05。结论本研究未发现研究人群的IGF-1（CA）重复序列多态性与ROP具有相关性。     

早产儿视网膜病的高危因素分析

目的了解我院早产儿视网膜病（refinopathy of prematurity,ROP）的发病状况,并对其高危因素进行分析。方法对2010年1月至2012年12月在我院新生儿科住院的早产儿（胎龄≤36周,体重≤2．5kg）,于生后2周进行ROP筛查,并定期随访。将患儿全身状况及吸氧、母孕期吸氧、先兆子痫、胎盘早剥等因素进行分析。结果255例患儿全部完成了眼底筛查,在周边视网膜血管化或病变退化后终止随访,发现ROP16例（26只眼）,ROP患病率为6．3％（5．1％）,其中Ⅰ期12例,Ⅱ期3例,Ⅲ期1例。高危因素分析示胎龄、出生体重、吸氧时间,吸氧浓度、机械通气与ROP相关（P〈0．05）;母孕期吸氧、先兆子痫、胎盘早剥等因素与ROP发病无关。结论早产、吸氧浓度高、机械通气是ROP的主要危险因素。对早产儿适时进行ROP筛查,并对发现的ROP早期进行有效视网膜激光光凝术,可控制病变,降低早产儿的致盲率。     

早产儿视网膜病变筛查及相关因素分析

目的：分析我院早产儿视网膜病变( retinopathy of prematurity,ROP)的发病情况,探讨其相关因素。方法回顾性分析2013年9月至2014年9月我院新生儿科住院的182例早产儿(出生体重<2000 g或胎龄<37周)的临床资料。于生后第4~6周或纠正胎龄32周进行ROP筛查,并定期随访。结果182例早产儿中筛查出不同程度ROP患儿32例,占17.6％,其中单眼10例,双眼22例。ROP患儿平均出生胎龄为(29.3±1.5)周,平均出生体重为(1280±240)g,其中ROP 1期11例,2期5例,3期16例,附加病变5例,住院期间18例患儿行视网膜激光光凝手术,2例行Lucentis球内注射。ROP组患儿与非ROP组在出生体重、胎龄、吸氧、肺表面活性物质应用、感染、窒息、输血方面比较,差异有统计学意义(P<0.05)。 Logistic回归分析显示胎龄、吸氧、机械通气、肺表面活性物质应用对ROP的发生有明显影响( P<0.05)。结论胎龄、出生体重、吸氧、呼吸暂停、感染等因素与ROP的发生有关,出生体重及胎龄越低,ROP发病率越高。     

早产儿视网膜病发病机制的研究进展

早产儿视网膜病(retinopathy of prematurity,ROP)是一种与早产儿相关的眼部疾病,特点是在视网膜发育过程中血管异常的发生,重症者可引起视网膜脱离而失明,是儿童视力障碍和失明的主要原因.ROP是一个复杂的疾病,除了目前发现的吸氧、胎龄小、低出生体重、细胞因子等因素以外,促红细胞生成素、感染等因素均是可能影响本病发生的因素,根据其发病机制,早期发现、早期治疗已愈发重要,现就ROP发病机制的研究现状及进展进行综述.     

血管内皮生长因子及胰岛素样生长因子-1在早产儿视网膜病变中的作用

早产儿视网膜病变(retinopathy of prematurity,ROP)多发生于早产儿尤其是极低出生体重儿,是导致儿童视力下降甚至失明的重要原因.视网膜新生血管形成是其主要的病理特点,血管内皮生长因子(vascular endothelial growth factor,VEGF)及胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)通过控制血管内皮细胞增殖,在新生血管形成中起到了关键作用.近年来临床研究表明,玻璃体内注射VEGF抑制剂及生后早期提高早产儿血清IGF-1水平是防治ROP的有效方法.该文以国内外相关研究为背景,综述VEGF及IGF-1在早产儿视网膜病变发病过程中的作用,以及针对其作用机制而采取的防治方法.     

Italian multicentre study on retinopathy of prematurity

The aim of this prospective multicentre study was to evaluate the influence of a number of perinatal factors on the development of ROP in high risk preterm infants with gestational age ≤30 weeks. All infants consecutively born in, or transferred to, one of the 14 participating centres from 1 January 1992 through 31 December 1993, who had a gestational age of 30 weeks or less and no congenital anomalies and survived to the age of 6 months, were included in the study. Of the 380 infants with mean ± SD gestational age of 28.4 ± 1.6 weeks (range 23–30 weeks) and birth weight of 1157 ± 335 g (range 485–2480 g) that were eligible for the study, 82 (21.5%) developed ROP stage 1 or 2 and 57 (15%) ROP stage 3 or 3+. Step-wise logistic regression analysis showed that the following factors had a significant predictive value for the development of ROP stage 3 or 3+: gestational age (Odds Ratio (OR)=0.6144 for each increment of 1 week of gestational age), birth weight (OR=0.843 for each increment of 100 g of birth weight), prenatal steroids (OR 4.044 for lacking or incomplete prophylaxis), RDS (OR 2.294), oxygen dependency at 60 days (OR 2.085), necrotising enterocolitis (OR 2.597). Conclusion This study confirms the role of prematurity, low birth weight and RDS in the pathogenesis of ROP, and emphasises the importance of prenatal steroid prophylaxis of RDS in very preterm infants. Furthermore, our data suggest that infants with oxygen dependency at 60 days or necrotising enterocolitis are at very high risk of developing ROP. Received: 29 September 1996 and in revised form: 28 January 1997 / Accepted: 1 April 1997     

早产儿视网膜病遗传易患性及相关基因的研究进展

目前,早产儿视网膜病仍是儿童致盲和视力损害的主要原因.它是一个多因素引起的疾病,除了早产、低体重及吸氧等原因,该病也存在遗传易患性,并有大量的基因参与其发病,对于这方面的研究能深入了解早产儿视网膜病的发病机制,为防治该病提供新的临床思路.     

早产儿视网膜病变相关因素分析

目的 探讨早产儿视网膜病变(retinopathy of prematurity,ROP)发病情况及相关危险因素.方法 回顾性分析2008年12月至2011年2月我院出生的1 356例体重2500 g以下或胎龄小于37周早产儿的临床资料,分为ROP组(n=208)和非ROP组(n=1148),分析全部早产儿自生后4～6周或矫正胎龄32周筛查眼底改变情况.结果 1356例早产儿中,208例发生ROP,发病率为15.34％,其中,严重病变36例(2.65％).与非ROP组相比,ROP组患儿在出生体重[(1 528 ±243)g vs(1 960±187)g]、胎龄[(30.92±0.72)周vs (32.87±1.28)周]、吸氧＞8d(123例vs 865例)、应用肺表面活性物质(18例vs 216例)、败血症(42例vs 154例)、宫内窘迫(63例vs 511例)、贫血(64例vs 237例)等方面比较,差异有统计学意义(P均＜0.05).Logistic回归分析结果显示出生体重、胎龄、吸氧＞8d、败血症及应用肺表面活性物质是ROP发生的高危因素(P＜0.05).同时,不同出生体重、不同胎龄患儿ROP发病率比较,差异均有统计学意义(P＜0.05).结论 出生体重及胎龄越低,ROP发病率越高,病变程度越严重.婴儿出生的成熟度越低,ROP尤其是严重ROP发病可能性越高.     

Maternal and neonatal factors associated with poor early weight gain and later retinopathy of prematurity

Aim: To identify factors associated with poor early weight gain as reflected in an alarm system, WINROP, and risk of later proliferative retinopathy of prematurity (ROP) in infants with gestational age (GA) < 28 weeks. Methods: Infants with a WINROP alarm and proliferative ROP, the ‘alarm group’ (n = 23), were matched to GA and gender to a ‘no alarm group’ (n = 23) with no WINROP alarm and no or mild ROP. Retrospectively maternal variables, birth characteristics and neonatal factors, during the first three postnatal weeks, were compared. Results: The ‘alarm group’ had lower birth weight (BW) and BW standard deviation score, longer stay in ventilator, more insulin and corticosteroid treatments, and lower white blood cell count. In a logistic regression model, BW standard deviation score, insulin, low white blood cell count, absence of both elevated C‐reactive protein and premature rupture of membranes were associated with proliferative ROP and WINROP alarm (p = 0.000, r² = 0.704). Conclusions: This study shows that prenatal factors resulting in low BW have persisting effects on early postnatal growth, metabolism and inflammatory response. Future prospective studies will focus on the link between these factors and pathological retinal vessel development in the early postnatal period to find possible preventive strategies.     

Perinatal infection, inflammation, and retinopathy of prematurity

The major known risk factors for retinopathy of prematurity (ROP) are extremely low gestational age, exposure to high levels of oxygen early after birth (phase I) and relatively lower oxygen levels later (phase II). In this review, we summarize recent data suggesting that exposure to perinatal infection/inflammation is associated with an increased risk for ROP. Part of this effect might be due to direct exposure of the developing retina to circulating products of infection and/or inflammation. Another potential mechanism that deserves exploration is that inflammation and/or oxidative stress can modify the known increased risk of oxygen-associated ROP. Taken together, accumulating evidence suggests that prenatal, perinatal, and postnatal systemic inflammation contribute to a 'pre-phase', sensitizing the pre-ROP retina for subsequent insults, setting the stage for what are now called phase I and phase II of ROP pathogenesis. Strategies targeting inflammatory responses might help reduce the risk for ROP in extremely low gestational age newborns.     

玻璃体腔内注射抗血管内皮生长因子治疗早产儿视网膜病复发的危险因素分析

目的 探讨玻璃体腔内注射抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗早产儿视网膜病(retinopathy of prematurity,ROP)的效果及复发的危险因素。方法 回顾性收集2016年1月—2021年12月在郑州大学第一附属医院出生行抗VEGF治疗的ROP患儿159例的临床资料,根据首次抗VEGF治疗后随访周期内ROP复发与否分为复发组(24例)和非复发组(135例),比较分析2组临床资料,采用多因素logistic回归分析探讨抗VEGF治疗ROP复发的危险因素。结果 经单次抗VEGF治疗后,所有159例患儿均显示附加病变消退。24例(15.1%)抗VEGF治疗后复发,复发平均时间为治疗后(8.4±2.6)周。多因素logistic回归分析显示,术前眼底出血、总用氧时间较长是ROP复发的危险因素(P<0.05),而妊娠高血压是保护因素(P<0.05)。结论 玻璃体腔内注射抗VEGF治疗ROP是有效的。术前眼底出血和氧疗时间较长可增加ROP复发的风险,而对于妊娠高血压对ROP复发的影响,还需进一步研究证实...     

Pathogenesis of retinopathy of prematurity

Retinopathy of prematurity (ROP) is a blinding disease, initiated by delayed retinal vascular growth after premature birth. There are both oxygen-regulated and non-oxygen-regulated factors, which contribute to both normal vascular development and retinal neovascularization. One important oxygen-regulated factor, critical to both phases of ROP, is vascular endothelial growth factor (VEGF). A critical non oxygen-regulated growth factor is insulin-like growth factor (IGF-1). In knockout mice, lack of IGF-1 prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro , low IGF-1 prevents vascular endothelial growth factor-induced activation of Akt, a kinase critical for vascular endothelial cell survival. Premature infants who develop ROP have lower levels of serum IGF-1 than age-matched infants without disease.
Conclusion : IGF-1 is critical to normal vascular development. Low IGF-1 predicts ROP and restoration of IGF-1 to normal levels may prevent ROP.     

Treatment of retinopathy of prematurity

Retinopathy of prematurity is a potentially blinding disorder of premature infants. Retinal ablation of the avascular retina originally described using cryotherapy but now most commonly undertaken with laser photocoagulation, reduces the unfavourable structural outcomes and improves the functional visual acuity outcome. The CRYO-ROP study showed the long-term benefit of treatment of threshold disease compared with no treatment, however even with cryoablation 44.4% of treated eyes had a visual acuity of 6/60 or worse at 10 year follow-up. The ETROP study of earlier treatment for high-risk pre-threshold disease, rather than treatment at threshold, has shown that pre-threshold treatment of type 1 disease produces a significantly improved outcome. Despite treatment some infants develop retinal detachment for which various surgical treatments have been described, although not always with a good functional outcome. Future treatment modalities may include the use of anti-VEGF therapies.     

Retinopathy of prematurity screening by non-retinologists

Objective To detect the screening efficiency of general ophthalmologists (ophthalmic residents) as well as nonophthalmologists (pediatric residents and nurses posted in neonatal intensive care unit) in screening (ROP) retinopathy of prematurity on the basis of posterior pole vascular changes. Methods Prospective consecutive review in a tertiary care hospital setting. Five groups (each, comprising of one ophthalmic resident, one pediatric resident and a nurse) examined the posterior pole vessels of 200 eyes of ROP with a direct ophthalmoscope and compared with an ROP specialist using indirect ophthalmoscope. SPSS (Statistical Package for the Social Science), version 10.0 was used for the analysis. Results Results Ophthalmic residents findings were: (sensitivity 95.68%, specificity 92.85%, positive predictive value 94.81%, negative predictive value 93.97%; pediatric residents findings were: (sensitivity 92.24%, specificity 88.09%, positive predictive value 91.45%, negative predictive value 89.15%); and nurses, finding were: (sensitivity 88.79%, specificity 85.71%, positive predictive value 89.56%, and negative predictive value 84.70%). The results had no statistically significant difference in diagnostic reliability. Kappa agreement analysis was significant for ophthalmic residents (0.887), pediatric residents (0.805) and nurses (0.744) compared with the ROP specialist. None of the children diagnosed with pre-threshold or threshold ROP was thought to have normal posterior pole vessels by the trainees. Conclusions Given adequate training, general ophthalmologists and non-ophthalmologists (pediatricians and nurse practitioners) are independently reliable in detecting posterior pole changes in ROP babies using direct ophthalmoscope and can be provided with a screening protocol.     

On the use of antiangiogenetic medications for retinopathy of prematurity

In contrast to the adult, the third-trimester foetus experiences one of the most intense periods of growth and maturation of its lifetime. Early development is characterized by the existence of critical periods when environmental factors effectively produce long-lasting changes. Proliferative retinopathy of prematurity (ROP) is a potentially blinding disease characterized by uncontrolled retinal angiogenesis. This pathologic angiogenesis is the target for two new treatment modalities for ROP, i.e. intravitreal anti-VEGF (bevacizumab) and systemic propranolol, which are being evaluated in ongoing or planned studies. VEGF is essential for normal angiogenesis in a growing infant, and the adrenergic system is important for many organ systems and, in addition, for plasticity of the visual and olfactory systems. CONCLUSION: This viewpoint raises concerns regarding the currently studied antiangiogenetic treatments for ROP and their possible general effects on the developing preterm infant.     

急进型后极部早产儿视网膜病的研究进展

急进型后极部早产儿视网膜病（AP-ROP）是一种特殊类型的早产儿视网膜病,其眼底特征表现为视网膜后极部血管扩张迂曲严重,并累及所有象限,而且病情进展非常迅猛。随着越来越多的AP-ROP 病例被发现,并且治疗效果相对差,使AP-ROP 问题日益受到关注。哪些早产儿更易患病？如何做到早期诊断？是否有更好的治疗技术？国内外对此进行了一定的研究探索。该文对AP-ROP 的危险因素、筛查、临床诊断、治疗的临床研究最新进展做一综述。