广州市番禺区早产儿视网膜病变筛查及结果分析
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摘要
研究背景
早产儿视网膜病变(retinopathy of prematurity, ROP)是早产儿和低体重儿发生的一种视网膜血管增生性病变。据世界卫生组织统计,目前在世界范围内ROP.已成为小儿失明的主要原因,占儿童致盲原因的6%～18%。世界卫生组织“视觉2020项目”已将ROP认定为高中收入水平国家的重要致盲因素之一,在美国则是位居第二的儿童致盲原因。随着重症监护技术在发展中国家的实施,更多的超低体质量出生儿存活,ROP亦将成为发展中国家儿童的重要致盲因素。随着我国医疗水平的不断发展,近年来新生儿科急救及护理技术的进步使得低体重婴儿及早产儿的死亡率下降,随之ROP的患病率也逐渐增加,由此造成的儿童盲也越来越多。
由于引起ROP的确切病因和发病机制还不十分清楚,目前尚无控制ROP发生、发展的有效药物。治疗ROP现阶段仍以手术治疗为主,晚期手术后视网膜得到部分或完全解剖复位,但患儿最终视功能的恢复极其有限,很少能恢复有用视力。因此对早产儿及低体重儿进行早期眼底筛查,发现ROP阈值病变并进行及时合理治疗,对降低ROP致盲率有着重要意义。
规范的ROP筛查重点在于合理统一的筛查标准,世界各国ROP筛查标准之间存在或多或少的差异。一般来说,一个国家或地区筛查标准是依据当地ROP的发生率及公认的各项危险因素分析所得出的结果而制定的。中华医学会在2004年的《早产儿治疗用氧和视网膜病变防治指南》中提出了我国的ROP筛查标准：对出生体重<2.0kg的早产儿和低体重儿进行眼底病变筛查,随诊直至周边视网膜血管化；对于患有严重疾病的早产儿筛查范围可适当扩大。黎晓新[7]认为,由于我国早产儿视网膜筛查时间不长,没有大量可靠的流行病学资料做支撑,因此我国筛查标准的依据不够充分,需要继续进行有关的研究,随着我国早产儿合理用氧后ROP发病特点的转变不断进行修正。
我国ROP筛查起步晚,筛查主要集中在全国比较发达地区的大医院,大多数三级医院均未很好开展,更未见二级及以下妇幼保健院开展ROP筛查工作的报道。由于各地区、各医疗机构ROP筛查对象不同,各自报道的发病率不同,目前尚难评估我国ROP的流行病学特点。三级医院救治的早产儿由于距离和花费高很容易失访,因此,我们要重视二级及以下医院早产儿视网膜筛查工作的开展。各级医院统一筛查对象及筛查工具,统一人才培训,所有数据统一分析,才能做到真正的流行病学研究。只有在十分可靠的流行病学基础上,才能得出准确的发病率,才能正确评估早产儿视网膜病变的发病风险,因而制定出最合适的筛查标准。
本研究用带视频录像的双目间接眼底镜对广州市番禺区的早产儿及低体重儿进行视网膜筛查,并将其结果进行分析,了解二级医院早产儿视网膜发育及眼底病变发生情况,探讨适合我国基层医院早产儿视网膜筛查的方法及标准,并为我国早产儿视网膜筛查多中心研究提供流行病学资料。据我们了解,本次研究首次对我国基层医院(二级医院)早产儿视网膜筛查结果进行研究报道,其筛查模式对我国其他二级医院开展ROP筛查工作将有很好的借鉴作用,其筛查结果对我国早产儿视网膜筛查、预防及流行病学研究有重大意义。
研究目的
了解我国二级医院早产儿视网膜发育特点及眼底病变发生情况,探讨适合我国基层医院早产儿视网膜筛查的方法及标准,并为我国早产儿视网膜筛查多中心研究提供流行病学资料。
研究方法
采用前瞻性研究方法,使用带视频录像的双目间接眼底镜对番禺区1270例早产儿进行眼底检查,观察视网膜发育及其眼底病变的发生情况,并将其结果与我国三级医院报到的结果进行比较分析。出生体重、出生胎龄及出生胎数与ROP发生之间的相关性采用卡方检验(SPSS13.0统计软件包),P<0.05为差异有统计学意义。
研究结果
1.正常早产儿眼底情况
排除14例早产儿视网膜病患儿,5例玻璃体病变患儿,32例视网膜出血患儿,2例视神经病变患儿,将本研究组1217例正常眼底早产儿根据矫正胎龄分为32-36周、37～40周、41-46周、大于46-周4个观察组,每组各含133例、603例、388例、93例早产儿。各组视盘发育情况、视网膜血管化及黄斑发育情况如下：(1)视盘形态学：本研究发现1217例正常早产儿中1016例早产儿(83.5%)视盘欠园,色淡,边界欠清,视杯不明显；201例视盘色淡红,边境清,视杯不明显。(2)黄斑部形态变化：在32-36周组133例早产儿中,105例黄斑轮廓不明显,占78.0%；14例黄斑轮廓清晰,占10.0%,隐约见黄斑反光晕,未见黄斑中心凹,黄斑部与周边视网膜颜色无明显变化。在37-40周组603例早产儿‘中,587例早产儿黄斑轮廓明显,占97.3%；575例黄斑部反光晕清晰可见,占95.3%。在41-46周组388例早产儿中,352例(90.7%)黄斑形态变化明显,中央部呈现明显的片状暗红色或红褐色,并形成一定程度凹陷,呈斜坡状,黄斑中心凹雏形形成,未见黄斑中心凹反射。大于46周组93例早产儿中,78例(83.9%)黄斑中心凹形成,可见中心凹反射。(3)视网膜血管化的形态变化：在32～36周组133例患儿中,81例(60.9%)后极部视网膜鼻侧动静脉血管主分支明显,血管条纹清晰,鼻侧周边视网膜开始出现次级分支血管,极周边部视网膜未完全血管化；133例(100%)颞侧视网膜为完全血管化。在37～40周组603例早产儿中,467例(77.4%)早产儿鼻侧视网膜完全血管化；237(50.7%)例早产儿后极部视网膜颞侧动静脉分支明显,血管条纹清晰,颞侧视网膜血管化范围已达颞侧视网膜Ⅱ区；187例(40.4%)颞侧视网膜血管已达锯齿缘,血管化已达Ⅲ区。在41-46周组388例早产儿中,388例(100%)鼻侧视网膜已完全血管化,鼻侧周边部视网膜次级血管条纹仍清晰可见,末梢血管接近锯齿缘,远端视网膜无混浊；357例(92%)颞侧视网膜血管化至颞侧Ⅲ区。大于46周组93例(100%)早产儿鼻颞侧视网膜完全血管化。
(4)视网膜色素类型在1217例正常早产儿中,901例(71%)视网膜颜色较深,呈青灰色,为视网膜型；278例(21.8%)呈轻度豹纹状眼底改变,为脉络膜型；91例(7.2%)颜色较淡,为巩膜型。876例(72%)早产儿眼底可以看到睫状后长神经。
2.早产儿眼底病变发生情况
(1)早产儿视网膜病变在本次研究的1270例早产低体重儿中,发现14例ROP患儿。12例随访病变消退,2例行激光治疗后病变消退。
(2)视网膜出血在1217例正常早产儿中,检查发现32例视网膜不同程度的出血,单眼20例,双眼12例。22例视网膜上见散在细小出血点,6例视网膜上见大片出血灶,4例仅在后极部见少数小出血点。32例均为自然分娩患儿,除1例ROP患儿外其余体重均大于2450g,4例有产钳史。随访4周后27例出血完全吸收,5例视网膜上仍可见痕迹。
(3)玻璃体病变在1217例正常早产儿中,检查发现5例玻璃体病变患儿。1例随访证实为玻璃体动脉残留；1例观察到眼底呈白色反光,后经彩色多谱勒超声及CT检查证实为永存性原始玻璃体增生症；2例玻璃体积血患者为双胞胎,极低出生体重儿,温箱喂养,怀疑为ROP,建议转上一级医院进一步诊治,因全身情况欠佳,家庭经济困难,患儿家属拒绝转院治疗,失访。1例患儿右眼玻璃体见大片团状灰白色浑浊物,视网膜结构不清,建议转上一级医院进一步检查,后确诊为视网膜母细胞瘤。
(4)视神经病变在1217例正常早产儿中,检查发现视乳头水肿2例,其中1例为新生儿缺氧缺血性脑病引起,1例后经证实为颅内高压所致。
3.检查致并发症发生情况
在检查过程前后,35例患儿发生不同程度的球结膜下出血,发生率为2.76%,随访2周后均自然消退。2例患儿头皮下见大量出血点,发生率为0.16%,随访1周后自然消退。1例患儿发生急性结膜炎,发生率为0.08%,涂用妥布霉素眼水及眼膏3天后好转,1周痊愈。28例患儿家属诉患儿筛查当天及随后几天睡觉时常惊叫,发生率为2.2%,1周左右症状消失。未发现有呼吸暂停、休克等严重并发症。
4.ROP发病情况
根据广州市的筛查标准,发现ROP者14例,如果按照卫生部的筛查标准进行筛查,发现ROP者13例,有1例ROP患者遗漏。其中,ROPⅢ区Ⅰ期者7例,Ⅲ区Ⅱ期者3例,Ⅲ区Ⅲ期者2例,Ⅱ区Ⅲ期者2例,未发现Ⅳ期及V期病变。达到阈值病变需要治疗的2例。
5.出生体重、胎龄、胎数与ROP发生的相关性
在检出的14例ROP中,出生体重在1000-1500g的11例,占此区间早产儿总例数52例的21.1%,占ROP总人数的78.6%(11/14)。出生体重在1501-2000g的2例,占此区间早产儿总例数182例的1.01%,占ROP总人数的14.3%(2/14)。出生体重在2001-2500g的1例,占此区间早产儿总例数688例的0.1%,占ROP总人数的7.1%(1/14)。未见有出生体重>2500g的早产儿患病。各组间比较x2=201.431,P=0.000<0.05,说明出生体重越小,ROP发表率越高,其差异具有统计学意义。
在检出的14例ROP中,出生胎龄在27-32周的11例,占此区间早产儿总例数110例的10%。出生胎龄在33-34周的2例,占此区间早产儿总例数207例的0.96%。出生胎龄在35-37的1例,占此区间早产儿总例数793例的0.1%。未见有出生胎龄>37周的早产儿患病。各组间比较x2=88.63,P=0.000<0.05,说明出生胎龄越小,ROP发表率越高,其差异具有统计学意义。
在检出的14例ROP中,单胎患病的的有10例,占所有单胞胎早产儿总例数1225例的0.82%；有4例双胞胎患儿患病,占总双胞胎人数45例的8.9%。两组间比较,x2=28.486,P=0.001<0.05,说明双胎者发生ROP的比率比单胎高,其差异具有统计学意义。本研究中,未发现有3及4胞胎患儿。
6.不同筛查标准ROP的发病率比较
按照广州市的筛查标准(所有出生<37周的早产儿或者出生体重<2500g的低体重儿),ROP发病率为1.1%(14/1270)。按照我国卫生部的筛查标准(所有出生体重<2000g的早产儿)计算,发病率为5.56%(13/234),如果按此标准进行筛查,遗漏2例Ⅲ区Ⅲ期ROP患儿,将少筛查1036例患儿,相当于受检儿的5倍。如果按照美国的筛查标准(出生体重<2000g或者出生胎龄<28周的早产儿),ROP发病率为21.1%(11/52),如果按此标准进行筛查,比按卫生部标准遗漏1例Ⅲ区Ⅱ期ROP患儿,将减少182例患儿,相当于受检者患儿的3.6倍。
7、与国内三级医院报道的发病率及筛查对象比较
我国近年来不同地区三级医院报道的早产儿发病率各地不同,除上海为6.6%外,其余在10%-20%之间。筛查工具除西安为RetCam外其余地区均主要为双目间接检眼镜,湖北深圳在双目间接检眼镜同时辅以RetCam。筛查对象各地区不同：北京、上海是儿童医院、妇幼保健院及综合医院住院部新生儿监护室的患儿；西安、湖北是综合医院儿科住院部及眼科门诊的患儿；湖南、广州是儿童医院住院部及眼科门诊患儿；广东是妇幼保健院住院及眼科门诊患儿,深圳为综合医院及妇幼保健院住院部及眼科医院眼科门诊的患儿。筛查对象出生体重范围为500-3500g,平均出生体重差别较大,广州市儿童医院为1256.2±268.1g；上海为1487.3±276.15g；北京、西安分别为1771.5±362.7g、1722.2-363.8g；广东、深圳为1650g；湖北为1972.2±478.3g。出生孕周范围为24-38.86w,出生平均孕周大部分在32周。
研究结论
1.早产儿眼底由于其解剖结构的发育不成熟,表现为与足月儿不同的特点,并随着年龄的增长而呈现一定的变化规律。大部分早产儿视网膜比正常早产儿发育迟缓。早产儿眼底大部分视盘欠园,色淡,边界欠清,视杯不明显。后极部视网膜动静脉血管条纹及其次级分支清晰可见。黄斑部轮晕明显,范围大,光反射强,大部分黄斑中心凹不明显。
2.早产儿由于胚胎发育异常、生产过程及母体疾病的影响常常会出现一些特殊的眼底病变。常见的有早产儿视网膜病变、视网膜出血、玻璃体动脉残留、永存性原始玻璃体增生症、视乳头水肿等。早产儿视网膜病变(ROP)是早产儿和低体重儿发生的一种视网膜血管增生性病变,其发病是以不成熟的视网膜为基础,发病机制不明,存在多种学说,目前支持导致ROP形成主要的有氧自由基学说、细胞因子学说和梭形细胞学说。ROP病因不明,早产、低出生体重为已公认的引起ROP的原因,低出生体重为ROP发生最主要的因素：出生体重越低,ROP的发生率越高；出生胎龄越低,ROP发病率越高。晚期手术对ROP患儿视功能无明显改善。早产儿视网膜病变的药物预防及早期药物干预治疗多年来一直在不断的探索中,目前尚无控制ROP发生、发展的有效药物。因此,早期筛查是目前预防ROP致盲的唯一有效手段。
3.数字化双目间接检眼镜检查系统既保留了双目间接眼底镜的“金标准”的优点,又增添了视频图像,提供了直观可靠的图片资料,同时还兼具价格低廉合理的优势,适合各层医院,尤其适合不发达国家基层医院推广应用。
4.复方托品酰胺眼药水用于早产儿散瞳检查未见明显并发症；在表麻下用双目间接眼底镜对早产儿进行视网膜检查是安全的,但为了减少患儿不适及家长的恐惧,我们建议检查医师要特别熟练,动作轻柔,尽量减少检查时间。
5.现阶段我国卫生部制定的筛查标准适合番禺地区ROP的筛查工作。是否需要将筛查标准的出生体重减少到1500g还需要大样本研究。由于本次研究时间较短,样本量相对不大,在以后的工作中,我们将按照卫生部制定的筛查标准继续加大样本量进行对比研究,以探讨出适合我国不同地区不同医院的最佳筛查标准。
6.由于各地区、各医疗机构ROP筛查对象不同,各自报道的发病率不同,目前尚难评估我国ROP的流行病学特点。要做到真正的流行病学研究,需要各级医院统一筛查对象及筛查工具,统一人才培训,所有数据统一分析。三级医院救治的早产儿由于距离和花费高很容易失访,因此,我们要重视二级及以下医院早产儿视网膜筛查工作的开展。据我们了解,本次研究首次对基层医院(二级医院)早产儿视网膜筛查结果进行研究报道,其筛查模式对我国其他二级医院开展ROP筛查工作将有很好的借鉴作用,其筛查结果对我国早产儿视网膜筛查、预防及流行病学研究有重大意义。
Background
Retinopathy of prematurity (ROP) is a proliferative vascular retinopathy, which occurs in low birth weight and premature infants. According to the World Health Organization (WHO), ROP is the main cause of blindness in children, with a prevalence of6%-18%in children with blindness. ROP has been recognized as one of the important factors bind to high income countries in "vision2020project" advocated by the world health organization (WHO).It is the second cause of children blindness in the United States. With the implement of intensive care technology in developed countries, more low body survivals. ROP will become a major factor of the blind causes of children in developing countries.In recent years, with the continuous development of our country medical treatment level, infants with low birth weight and premature mortality decline under new advances in pediatric first-aid and nursing. Meanwhile, the prevalence of ROP, and the amount of blind children due to ROP are also gradually increased.
Since the exact pathogenesis of ROP is still unclear, the efficacy of surgery in the advanced stages of ROP is limited and variable. Even if retinal surgery appropriately repositions the detached retina, recovery of the patients'visual function remains limited. Therefore, early screening and an appropriate treatment for early ROP is vital to reduce the rate of blindness in low birth weight and premature infants. In2004, the ministry of health has issued "the premature treatment with oxygen and retinopathy prevention guide". Since then, many screening results from big hospitals (Level of Class III and Grade A) have been reported in China, but there is no reports from basic-level hospitals. So, we screened the retina of premature and low birth weight babies in the panyu district at Guangzhou with binocular indirect ophthalmoscope which incorporated with a video recordingsystem.
The key of standardization of ROP screening is to set a reasonable and unified screening standard. There are more or less differences between the ROP screening standards around the world. In general, the screening standard of a country or region was set on the basis of the risk factors and the analysis of recognized results at local city. The ROP screening standard of China was put forward by the Chinese Medical Association in2004in the guideline "Guide and treatment for premature infants with oxygen and ROP prevention ". This standard is as the following:Ocular fundus screening for premature and low birth weight (less than2.0kg) infants, and the follow-up should be continued until the peripheral retinal becomes neovascularization. It is appropriate to expand the scope of ROP screening in those infants with serious disease. But Li Xiaoxin said that the screening standard of our country is inadequate on the basis of lack of enough time number of reliable epidemiological data. So we need continue to conduct relevant research, along with reasonable use of oxygen after ROP onset in the circumstance of a continuous correction nt the characteristics of ROP in our country.
The ROP screening started late in China, and mainly concentrated in the large hospitals of developed areas. It is not well completed in most of Grade III hospitals, rather than the maternal and child health hospitals at the level of Grade II and the lower. Because the different object of ROP screening in various medical institutions of different regions and the different incidence rate among respective reports, it is difficult to evaluate the epidemiological characteristics of ROP in China. Treatment of premature infants in hospitals of Grade III is very difficult to be done due to far distance and high cost. Therefore, we should pay more attention to the screening of retinopathy of prematurity in the hospitals of grade two and below. The screening object, standard tool, its training and data analysis in all levels of hospital should be unified, in order to achieve a satisfactory epidemiological study. The accurate incidence, correct risk evaluation of ROP and the most appropriate screening criteria can be achieved based only on the reliable epidemiological research.
In this study, binocular indirect ophthalmoscope with video was used for retinal screening of premature and low birth weight infants in the Panyu District of Guangzhou city. The results were analyzed in order to understand retina development of premature infants and the occurrence of retinopathy in Grade II hospitals and find a suitable method and a standard for screening retinopathy of prematurity at primary hospitals in our country, and to provide epidemiological data for multicenter study on retinopathy of prematurity screening in our country. To our knowledge, this study is the first report on retinopathy of prematurity screening amnong the grass-roots hospitals in China. The screening model will be a good reference for ROP screening in the other Grade II hospitals. The screening results of the premature infants are of great significance for preventive research and epidemiological screening in China.
Objective
To investigate the characteristics of the retinal development of premature infants in the secondary hospitals in China. To explore a suitable ROP screening method and standard for hospitals of basic level in China in order to provide epidemiological data for multicenter study on ROP screening.
Methods
This prospective study enrolled1270premature infants for ROP screening. The procedures were examined by using a computer-assisted imaging system of binocular indirect ophthaimoscope. The development of retina was observed and the fundus lesions were recorded and compared with other basic level hospitals in China. The relationship of birth weight, gestational age at birth or the number of embryos and the occurrence of ROP was analysed by chi-square test with SPSS software. It is regarded as statistically significance if the p value of difference is less than0.05.
Results
1. Normal performance of premature retina:
Except the14cases with ROP patients,5cases had vitreous lesions,32cases had retinal hemorrhage,2cases had optic neuropathy patients. According to the research group, the corrected gestational age of1217cases with normal fundus is divided into32-36weeks,37-40weeks,41-46weeks, and greater than46weeks.There were133,603,388, and603premature infants in each group respectively. OPTIC CUPThe retinal developmentsuch as retinal vascularization and macular development is as follows:
(1) the morphology of optic cup:In the1217normal infants, the optic cups od1016cases of premature infants (83.5%) showed waned, light color, unclear borders, optic cup is not obvious;. The optic cups of201cases are reddish, with clear border. The optic cup is not obvious.
(2) Macular morphology:In the32-36weeks group with133cases of premature infants, the macular contour of105cases is not obvious, accounted for78.0%.14cases had clear macular outline (10.0%). The macular halo was ambiguously seen, the macular fovea did not see. The color of macular and peripheral retina did not change. In the37-40weeks group with603cases of premature infants, macular outline is obvious in587cases of premature infant, accounted for97.3%; macular anti halation is clearly visible in575cases, accounted for95.3%. In the41-46weeks group with388cases of premature infants, macular morphology changes obviously in352cases (90.7%),, the central part of retinal fovea presented obvious flake dark red or reddish brown, and formed a certain degree of sag with slope shape. A concave shape of macular center formed, without macular fovea reflex. In the greater than46weeks group with93cases of premature infants, macular fovea formation with visible foveal reflex presented in78cases (83.9%).
(3) The morphological change of retinal vascularization:In the32-36weeks group with133cases, the pole of retina behind nasal side arteriovenous vascular branches were obvious in81cases (60.9%). In these cases, the blood vessels and the stripes were clear, the nasal side of retina started to show secondary branch blood vessels,. Thesurrounding retina was not completely vascularized. The retina of temporal side was completely vascularized in133cases (100%),. In the37-40weeks group with603cases of premature infants, premature retina at nasal lateral was completely vascularized in467cases (77.4%).;237(50.7%) cases of premature infants presented obviousarteriovenous branches after the pole of the temporal retina. The blood vessels and the stripes are clear, the temporal range with retinal vascularization reached its temporal retina II area. The temporal retinal blood vessels have serrated edge in187cases (40.4%), vascularization reached III area. In the41-46weeks group with388cases of premature infants, the retina at nasal side has completely retinal vascularization in388cases (100%). The secondary retinal blood vessels surrounding the nasal side stripe are still clearly visible. The peripheral blood vessels near serrated edge and distal retina did not present cloudy. The lateral temporal retina was vascularized from areaⅢ to the temporal side in357cases (92%). In the greater than46weeks group,93cases (100%) had completely vascularized premature nasal lateral temporal retina.
(4)The types of retina pigment:Among the1217normal cases,901cases (71%) had retinal darker and pewter.278cases (21.8%) had mild leopard shaped fundus change. For the choroid type,91cases (7.2%) had lighter color sclera. The premature fundus can be seen in876cases (72%), after long ciliary nerve.
2. The occurrence of dfundus disease:
(1)ROP:In the study of1270cases,14cases of children had ROP. The lesions subsided in12cases during follow-up, The lesions subsided in2cases after laser treatment.
(2) retinal hemorrhage:In the1217normal cases,32cases had varied degrees of retinal hemorrhage.20cases were monocular,12cases were binocular.22cases of retina had small bleeder,6cases of retina had large focal hemorrhage,4cases had a few small bleeder in the pole.32cases were natural birth child. The weight of1case of ROP children was greater than2450g.4cases had a history of forceps. The bleeding was completely absorbed in27cases after4weeks follow-up. The retina is still visible traces in5cases.
(3) Vitreous lesions:In the1217normal cases,5cases had vitreous lesions.1case was confirmed as residual vitreous artery;1case was observed with a white eye glance, which was confirmed by color doppler ultrasound and CT examination for permanence original vitreous hyperplasia.2twins had vitreous hemorrhage. For very low birth weight, temperature box feeding, and doubt ROP, the infants were recommended to a higher level hospital to make a diagnosis and give treatment. Those infants due to poor general condition and family economic difficulties, their parents refused to transfer them to a better treatment and then missed follow-up.1case had large clumps gray haze in the vitreous, retinal structure is not clear, was suggested to turn to the next higher level hospitals for further examination, after the diagnosis of retinoblastoma.
(4) Optic neuropathy:In1217normal infants, examination showed apparent papilla edema in2cases, neonatal hypoxic ischemic encephalopathy in1cases.1case was confirmed as intracranial pressure.
3. Complications:Before and after the inspection process,35cases occurred with different degrees of ball subconjunctival hemorrhage. The incidence was2.76%, and natural faded after2weeks follow-up.2cases had massive haemorrhage under the scalp. The incidence is0.16%and was natural faded after1week follow-up.1case had acute conjunctivitis and was treated with tobramycin eyedrops and eye ointment for3days. The rate is0.08%, and was healed in1week.28cases underwent screening and often exclaimed. The incidence was2.2%, and the symptoms disappeared in around1week. Serious complications such as apneaand shock have not been found.
4. ROP:According to the screening criteria of Guangzhou city,14cases had ROP. If according to the screening standard set by the ministry of health,13cases had ROP. Among them,7cases is in III area I period;3cases is in III area Ⅱ period,2cases is in III area III period,2casesis in II area III period. No cases were found in stage IV and V lesions.2cases with threshold lesions needed treatment.
5. Birth weight, gestational age, and their relationships with ROP
In the14cases of ROP,11cases birth weighed from1000to1500g, accounted for21.1%of the total52cases, accounting for78.6%of the total number of ROP (11/14).2cases weighed from1501to2000g, accounting for1.01%of the182cases total, accounting for14.3%of the total number of ROP (2/14).1case weighed among2001-2500g, accounting for0.1%of the688cases total, accounting for7.1%of the total number of ROP (1/14). No premature illness was found whenthe birth weight was greater than2500g (x2=201.431, P=0.000<0.05), suggesting that the smaller the birth weigh, a higher ROP rate. The difference is statistically significant.
In the14cases with ROP,11cases were born in27to32weeks of gestational age, accounting for10%of110total cases.2cases was33-34weeks gestational age, accounting for0.96%of the207total cases.1case was35to37weeks gestational age at birth, accounting for0.1%of the793total cases. No birth gestational age greater than37weeks was noted with premature illness(x2=88.63, P=0.000<0.05), suggesting that smaller the gestational age, higher the ROP rateat birth. The difference is statistically significant.
In the14cases of ROP,10cases were singleton, saccounting for0.82%of the total cases1225cases of premature infants. There are4twins, accounting for8.9%of the total of45twins (x2=28.486, P=0.001<0.05), suggesting that the incidence of ROP in twins is higher than singletons. The difference is statistically significant.
6. Comparison of the incidence of ROP between different screening standards
According to Guangzhou screening criteria (<37weeks premature birth or birth weight2500g), the prevalence of ROP in low birth-weight infants was1.1%(14/1270). According to screening standard issued by Chinese ministry of health, the incidence was5.56%(13/234). If according to this standard screening,2cases with III area III ROP were missed. Children will have less screening,1036cases were tested5times. According to the screening criteria (<2000g birth weight or gestational age<28weeks premature babies), incidence of ROP is21.1%(11/52).According to this standard by the ministry of health,1case with II period III area ROP was missed., The amount of infant with ROP will reduce182cases, equivalent to21.1%of examined children.
7. Comparion with other domestic tertiary hospitals on the incidence and screening object
In recent years, the incidence of premature infants reported by the tertiary hospitals variable in our country. The incidence of premature infants in Shanghai is6.6%, the rest is from10%to-20%. Screening tool in Xi'an city was the RetCam. The rest used the binocular indirect ophthalmoscope. RetCam as a complementary and binocular indirect ophthalmoscope at the same time was used Hubei and shenzhen. The object of screening was different:Beijing and Shanghai is a children's hospital, maternal and child health care or comprehensive hospital inpatient children with neonatal unit. In xi'an and Hubei general hospital, the object is pediatric inpatient and ophthalmic outpatient children.The object is a children's hospital inpatient and ophthalmic outpatient children in Hunan and Guangzhou. It is the maternity and child care hospital and an eye clinic in Guangdong. Children in shenzhen were from comprehensive hospitals, health care of women and children, the inpatients of ophthalmology and eye hospital outpatient service. The birth weight for screening object ranged from500-3500g. The difference of birth weight is large. The birth weight at Guangzhou children's hospital was1256.2+/-268.1g;1487.3+/-276.15g a Shangha;1771.5+/-362.7g at Beijing, and1722.2+/-363.8g at Xi 'an,1650g atGuangdong Shenzhen,1972.2+478.3g at Hubei. Birth gestational age ranged from24to38.86weeks. The average gestational age at birth was32weeks.
Conclusion
1. Premature fundus, have different characteristics according to the growth of the age due to its amature development of anatomical structure. Most retinas of ROP retard development than normal preterm infants. Most OPTIC CUPfundus are not round with mild color and unclear cup rims. The retinal veins of the posterior retina showed stripe type and visible branch. The macular halo is obvious with intense reflection, its range is big. Most macular foveas are not obvious.
2. Preterm infants usually had some special lesions in the fundus due to abnormal embryonic development, the production process and the maternal disease.. Premature retinopathy, retinal hemorrhage, vitreous artery residual, persistent primary vitreous hyperplasia, papillary edema are very commonly appeared. Retinopathy of prematurity (ROP) is a kind of retinal vascular proliferative lesions happens in premature and low birth weight babie. It is based on immature retinal disease. Its pathogenesis is unclear. There are many theoriesexplain the formation of ROP as free oxygen radicals theory,cytokine and spindle cells theories. The etiology of ROP was unknown. Premature birth and low birth weight have been recognized as the cause of ROP. Low birth weight is the major cause of ROP. Lower the birth weight, higher the incidence of ROP. Lesser the birth gestational age, higher the incidence of ROP. If give late operation for ROP, visual function has not significant improvement in children. The pharmaceutical prevention and its early intervention for premature retinopathy have been in investigation for years. There is no currently effective drug for controlling ROP occurrence and development. Therefore, early screening is the only effective way to prevent blindness due to ROP.
3. Our results showed that the digital binocular indirect ophthalmoscope system can reliably and directly provide clear digital images and videos of the peripheral retina. This system has several advantages. It provides accurate high-quality images. It is affordable, and it remains the advantages of the "gold standard" binocular indirect ophthalmoscope. Because of its low price, it is suitable for screening ROP in all small hospitals, especially primary hospitals in China.
4. The compound tropicamide eye drops did not show obvious complications for mydriatic inspection in premature babies. The on-table examination with binocular indirect ophthalmoscope is safe for premature retina in infanst. But for reducing the fear of parents and children and the testing time, we suggest a skilled, special trained and gentle doctor.
5. The screening standard set by the ministry of health in China works well for ROP screening in the Panyu district at present. It still needs further research of large sample to decide whether the minimal weight of infant for enrollment should reduce to1500g. The study period is short, the sample size is relatively small. In the later work, we will continue to increase the sample size in accordance with the standards set by the ministry of health screening, in order to investigate the best suitable threshold of screening criteria in for different regional hospital in China.
6. Due to different objective of ROP screening in various areas and various medical institutions, the incidence is also variable. It is difficult to assess the epidemiological characteristics of ROP. A uniform screening object and screening tool has to be needs or unified training and analysis of all data in all levels of hospital for epidemiological studies. Because of far distance and high cost, it's easy to miss the follow-up in tertiary hospital. Therefore, we should focus ROP screening work on the secondary and even lower hospitals. As far as we know, this is the first study on ROP screening in the basic-level hospitals (second class hospital). The screening model for other secondary hospitals in our country to carry out the ROP screening work will have a very good model function. The results of retina screening, its prevention and epidemiology research for premature infants in China has great significance.
早产儿视网膜病变(retinopathy of prematurity, ROP)是早产儿和低体重儿发生的一种视网膜血管增生性病变。据世界卫生组织统计,目前在世界范围内ROP.已成为小儿失明的主要原因,占儿童致盲原因的6%～18%。世界卫生组织“视觉2020项目”已将ROP认定为高中收入水平国家的重要致盲因素之一,在美国则是位居第二的儿童致盲原因。随着重症监护技术在发展中国家的实施,更多的超低体质量出生儿存活,ROP亦将成为发展中国家儿童的重要致盲因素。随着我国医疗水平的不断发展,近年来新生儿科急救及护理技术的进步使得低体重婴儿及早产儿的死亡率下降,随之ROP的患病率也逐渐增加,由此造成的儿童盲也越来越多。
由于引起ROP的确切病因和发病机制还不十分清楚,目前尚无控制ROP发生、发展的有效药物。治疗ROP现阶段仍以手术治疗为主,晚期手术后视网膜得到部分或完全解剖复位,但患儿最终视功能的恢复极其有限,很少能恢复有用视力。因此对早产儿及低体重儿进行早期眼底筛查,发现ROP阈值病变并进行及时合理治疗,对降低ROP致盲率有着重要意义。
规范的ROP筛查重点在于合理统一的筛查标准,世界各国ROP筛查标准之间存在或多或少的差异。一般来说,一个国家或地区筛查标准是依据当地ROP的发生率及公认的各项危险因素分析所得出的结果而制定的。中华医学会在2004年的《早产儿治疗用氧和视网膜病变防治指南》中提出了我国的ROP筛查标准：对出生体重<2.0kg的早产儿和低体重儿进行眼底病变筛查,随诊直至周边视网膜血管化；对于患有严重疾病的早产儿筛查范围可适当扩大。黎晓新[7]认为,由于我国早产儿视网膜筛查时间不长,没有大量可靠的流行病学资料做支撑,因此我国筛查标准的依据不够充分,需要继续进行有关的研究,随着我国早产儿合理用氧后ROP发病特点的转变不断进行修正。
我国ROP筛查起步晚,筛查主要集中在全国比较发达地区的大医院,大多数三级医院均未很好开展,更未见二级及以下妇幼保健院开展ROP筛查工作的报道。由于各地区、各医疗机构ROP筛查对象不同,各自报道的发病率不同,目前尚难评估我国ROP的流行病学特点。三级医院救治的早产儿由于距离和花费高很容易失访,因此,我们要重视二级及以下医院早产儿视网膜筛查工作的开展。各级医院统一筛查对象及筛查工具,统一人才培训,所有数据统一分析,才能做到真正的流行病学研究。只有在十分可靠的流行病学基础上,才能得出准确的发病率,才能正确评估早产儿视网膜病变的发病风险,因而制定出最合适的筛查标准。
本研究用带视频录像的双目间接眼底镜对广州市番禺区的早产儿及低体重儿进行视网膜筛查,并将其结果进行分析,了解二级医院早产儿视网膜发育及眼底病变发生情况,探讨适合我国基层医院早产儿视网膜筛查的方法及标准,并为我国早产儿视网膜筛查多中心研究提供流行病学资料。据我们了解,本次研究首次对我国基层医院(二级医院)早产儿视网膜筛查结果进行研究报道,其筛查模式对我国其他二级医院开展ROP筛查工作将有很好的借鉴作用,其筛查结果对我国早产儿视网膜筛查、预防及流行病学研究有重大意义。
研究目的
了解我国二级医院早产儿视网膜发育特点及眼底病变发生情况,探讨适合我国基层医院早产儿视网膜筛查的方法及标准,并为我国早产儿视网膜筛查多中心研究提供流行病学资料。
研究方法
采用前瞻性研究方法,使用带视频录像的双目间接眼底镜对番禺区1270例早产儿进行眼底检查,观察视网膜发育及其眼底病变的发生情况,并将其结果与我国三级医院报到的结果进行比较分析。出生体重、出生胎龄及出生胎数与ROP发生之间的相关性采用卡方检验(SPSS13.0统计软件包),P<0.05为差异有统计学意义。
研究结果
1.正常早产儿眼底情况
排除14例早产儿视网膜病患儿,5例玻璃体病变患儿,32例视网膜出血患儿,2例视神经病变患儿,将本研究组1217例正常眼底早产儿根据矫正胎龄分为32-36周、37～40周、41-46周、大于46-周4个观察组,每组各含133例、603例、388例、93例早产儿。各组视盘发育情况、视网膜血管化及黄斑发育情况如下：(1)视盘形态学：本研究发现1217例正常早产儿中1016例早产儿(83.5%)视盘欠园,色淡,边界欠清,视杯不明显；201例视盘色淡红,边境清,视杯不明显。(2)黄斑部形态变化：在32-36周组133例早产儿中,105例黄斑轮廓不明显,占78.0%；14例黄斑轮廓清晰,占10.0%,隐约见黄斑反光晕,未见黄斑中心凹,黄斑部与周边视网膜颜色无明显变化。在37-40周组603例早产儿‘中,587例早产儿黄斑轮廓明显,占97.3%；575例黄斑部反光晕清晰可见,占95.3%。在41-46周组388例早产儿中,352例(90.7%)黄斑形态变化明显,中央部呈现明显的片状暗红色或红褐色,并形成一定程度凹陷,呈斜坡状,黄斑中心凹雏形形成,未见黄斑中心凹反射。大于46周组93例早产儿中,78例(83.9%)黄斑中心凹形成,可见中心凹反射。(3)视网膜血管化的形态变化：在32～36周组133例患儿中,81例(60.9%)后极部视网膜鼻侧动静脉血管主分支明显,血管条纹清晰,鼻侧周边视网膜开始出现次级分支血管,极周边部视网膜未完全血管化；133例(100%)颞侧视网膜为完全血管化。在37～40周组603例早产儿中,467例(77.4%)早产儿鼻侧视网膜完全血管化；237(50.7%)例早产儿后极部视网膜颞侧动静脉分支明显,血管条纹清晰,颞侧视网膜血管化范围已达颞侧视网膜Ⅱ区；187例(40.4%)颞侧视网膜血管已达锯齿缘,血管化已达Ⅲ区。在41-46周组388例早产儿中,388例(100%)鼻侧视网膜已完全血管化,鼻侧周边部视网膜次级血管条纹仍清晰可见,末梢血管接近锯齿缘,远端视网膜无混浊；357例(92%)颞侧视网膜血管化至颞侧Ⅲ区。大于46周组93例(100%)早产儿鼻颞侧视网膜完全血管化。
(4)视网膜色素类型在1217例正常早产儿中,901例(71%)视网膜颜色较深,呈青灰色,为视网膜型；278例(21.8%)呈轻度豹纹状眼底改变,为脉络膜型；91例(7.2%)颜色较淡,为巩膜型。876例(72%)早产儿眼底可以看到睫状后长神经。
2.早产儿眼底病变发生情况
(1)早产儿视网膜病变在本次研究的1270例早产低体重儿中,发现14例ROP患儿。12例随访病变消退,2例行激光治疗后病变消退。
(2)视网膜出血在1217例正常早产儿中,检查发现32例视网膜不同程度的出血,单眼20例,双眼12例。22例视网膜上见散在细小出血点,6例视网膜上见大片出血灶,4例仅在后极部见少数小出血点。32例均为自然分娩患儿,除1例ROP患儿外其余体重均大于2450g,4例有产钳史。随访4周后27例出血完全吸收,5例视网膜上仍可见痕迹。
(3)玻璃体病变在1217例正常早产儿中,检查发现5例玻璃体病变患儿。1例随访证实为玻璃体动脉残留；1例观察到眼底呈白色反光,后经彩色多谱勒超声及CT检查证实为永存性原始玻璃体增生症；2例玻璃体积血患者为双胞胎,极低出生体重儿,温箱喂养,怀疑为ROP,建议转上一级医院进一步诊治,因全身情况欠佳,家庭经济困难,患儿家属拒绝转院治疗,失访。1例患儿右眼玻璃体见大片团状灰白色浑浊物,视网膜结构不清,建议转上一级医院进一步检查,后确诊为视网膜母细胞瘤。
(4)视神经病变在1217例正常早产儿中,检查发现视乳头水肿2例,其中1例为新生儿缺氧缺血性脑病引起,1例后经证实为颅内高压所致。
3.检查致并发症发生情况
在检查过程前后,35例患儿发生不同程度的球结膜下出血,发生率为2.76%,随访2周后均自然消退。2例患儿头皮下见大量出血点,发生率为0.16%,随访1周后自然消退。1例患儿发生急性结膜炎,发生率为0.08%,涂用妥布霉素眼水及眼膏3天后好转,1周痊愈。28例患儿家属诉患儿筛查当天及随后几天睡觉时常惊叫,发生率为2.2%,1周左右症状消失。未发现有呼吸暂停、休克等严重并发症。
4.ROP发病情况
根据广州市的筛查标准,发现ROP者14例,如果按照卫生部的筛查标准进行筛查,发现ROP者13例,有1例ROP患者遗漏。其中,ROPⅢ区Ⅰ期者7例,Ⅲ区Ⅱ期者3例,Ⅲ区Ⅲ期者2例,Ⅱ区Ⅲ期者2例,未发现Ⅳ期及V期病变。达到阈值病变需要治疗的2例。
5.出生体重、胎龄、胎数与ROP发生的相关性
在检出的14例ROP中,出生体重在1000-1500g的11例,占此区间早产儿总例数52例的21.1%,占ROP总人数的78.6%(11/14)。出生体重在1501-2000g的2例,占此区间早产儿总例数182例的1.01%,占ROP总人数的14.3%(2/14)。出生体重在2001-2500g的1例,占此区间早产儿总例数688例的0.1%,占ROP总人数的7.1%(1/14)。未见有出生体重>2500g的早产儿患病。各组间比较x2=201.431,P=0.000<0.05,说明出生体重越小,ROP发表率越高,其差异具有统计学意义。
在检出的14例ROP中,出生胎龄在27-32周的11例,占此区间早产儿总例数110例的10%。出生胎龄在33-34周的2例,占此区间早产儿总例数207例的0.96%。出生胎龄在35-37的1例,占此区间早产儿总例数793例的0.1%。未见有出生胎龄>37周的早产儿患病。各组间比较x2=88.63,P=0.000<0.05,说明出生胎龄越小,ROP发表率越高,其差异具有统计学意义。
在检出的14例ROP中,单胎患病的的有10例,占所有单胞胎早产儿总例数1225例的0.82%；有4例双胞胎患儿患病,占总双胞胎人数45例的8.9%。两组间比较,x2=28.486,P=0.001<0.05,说明双胎者发生ROP的比率比单胎高,其差异具有统计学意义。本研究中,未发现有3及4胞胎患儿。
6.不同筛查标准ROP的发病率比较
按照广州市的筛查标准(所有出生<37周的早产儿或者出生体重<2500g的低体重儿),ROP发病率为1.1%(14/1270)。按照我国卫生部的筛查标准(所有出生体重<2000g的早产儿)计算,发病率为5.56%(13/234),如果按此标准进行筛查,遗漏2例Ⅲ区Ⅲ期ROP患儿,将少筛查1036例患儿,相当于受检儿的5倍。如果按照美国的筛查标准(出生体重<2000g或者出生胎龄<28周的早产儿),ROP发病率为21.1%(11/52),如果按此标准进行筛查,比按卫生部标准遗漏1例Ⅲ区Ⅱ期ROP患儿,将减少182例患儿,相当于受检者患儿的3.6倍。
7、与国内三级医院报道的发病率及筛查对象比较
我国近年来不同地区三级医院报道的早产儿发病率各地不同,除上海为6.6%外,其余在10%-20%之间。筛查工具除西安为RetCam外其余地区均主要为双目间接检眼镜,湖北深圳在双目间接检眼镜同时辅以RetCam。筛查对象各地区不同：北京、上海是儿童医院、妇幼保健院及综合医院住院部新生儿监护室的患儿；西安、湖北是综合医院儿科住院部及眼科门诊的患儿；湖南、广州是儿童医院住院部及眼科门诊患儿；广东是妇幼保健院住院及眼科门诊患儿,深圳为综合医院及妇幼保健院住院部及眼科医院眼科门诊的患儿。筛查对象出生体重范围为500-3500g,平均出生体重差别较大,广州市儿童医院为1256.2±268.1g；上海为1487.3±276.15g；北京、西安分别为1771.5±362.7g、1722.2-363.8g；广东、深圳为1650g；湖北为1972.2±478.3g。出生孕周范围为24-38.86w,出生平均孕周大部分在32周。
研究结论
1.早产儿眼底由于其解剖结构的发育不成熟,表现为与足月儿不同的特点,并随着年龄的增长而呈现一定的变化规律。大部分早产儿视网膜比正常早产儿发育迟缓。早产儿眼底大部分视盘欠园,色淡,边界欠清,视杯不明显。后极部视网膜动静脉血管条纹及其次级分支清晰可见。黄斑部轮晕明显,范围大,光反射强,大部分黄斑中心凹不明显。
2.早产儿由于胚胎发育异常、生产过程及母体疾病的影响常常会出现一些特殊的眼底病变。常见的有早产儿视网膜病变、视网膜出血、玻璃体动脉残留、永存性原始玻璃体增生症、视乳头水肿等。早产儿视网膜病变(ROP)是早产儿和低体重儿发生的一种视网膜血管增生性病变,其发病是以不成熟的视网膜为基础,发病机制不明,存在多种学说,目前支持导致ROP形成主要的有氧自由基学说、细胞因子学说和梭形细胞学说。ROP病因不明,早产、低出生体重为已公认的引起ROP的原因,低出生体重为ROP发生最主要的因素：出生体重越低,ROP的发生率越高；出生胎龄越低,ROP发病率越高。晚期手术对ROP患儿视功能无明显改善。早产儿视网膜病变的药物预防及早期药物干预治疗多年来一直在不断的探索中,目前尚无控制ROP发生、发展的有效药物。因此,早期筛查是目前预防ROP致盲的唯一有效手段。
3.数字化双目间接检眼镜检查系统既保留了双目间接眼底镜的“金标准”的优点,又增添了视频图像,提供了直观可靠的图片资料,同时还兼具价格低廉合理的优势,适合各层医院,尤其适合不发达国家基层医院推广应用。
4.复方托品酰胺眼药水用于早产儿散瞳检查未见明显并发症；在表麻下用双目间接眼底镜对早产儿进行视网膜检查是安全的,但为了减少患儿不适及家长的恐惧,我们建议检查医师要特别熟练,动作轻柔,尽量减少检查时间。
5.现阶段我国卫生部制定的筛查标准适合番禺地区ROP的筛查工作。是否需要将筛查标准的出生体重减少到1500g还需要大样本研究。由于本次研究时间较短,样本量相对不大,在以后的工作中,我们将按照卫生部制定的筛查标准继续加大样本量进行对比研究,以探讨出适合我国不同地区不同医院的最佳筛查标准。
6.由于各地区、各医疗机构ROP筛查对象不同,各自报道的发病率不同,目前尚难评估我国ROP的流行病学特点。要做到真正的流行病学研究,需要各级医院统一筛查对象及筛查工具,统一人才培训,所有数据统一分析。三级医院救治的早产儿由于距离和花费高很容易失访,因此,我们要重视二级及以下医院早产儿视网膜筛查工作的开展。据我们了解,本次研究首次对基层医院(二级医院)早产儿视网膜筛查结果进行研究报道,其筛查模式对我国其他二级医院开展ROP筛查工作将有很好的借鉴作用,其筛查结果对我国早产儿视网膜筛查、预防及流行病学研究有重大意义。
Background
Retinopathy of prematurity (ROP) is a proliferative vascular retinopathy, which occurs in low birth weight and premature infants. According to the World Health Organization (WHO), ROP is the main cause of blindness in children, with a prevalence of6%-18%in children with blindness. ROP has been recognized as one of the important factors bind to high income countries in "vision2020project" advocated by the world health organization (WHO).It is the second cause of children blindness in the United States. With the implement of intensive care technology in developed countries, more low body survivals. ROP will become a major factor of the blind causes of children in developing countries.In recent years, with the continuous development of our country medical treatment level, infants with low birth weight and premature mortality decline under new advances in pediatric first-aid and nursing. Meanwhile, the prevalence of ROP, and the amount of blind children due to ROP are also gradually increased.
Since the exact pathogenesis of ROP is still unclear, the efficacy of surgery in the advanced stages of ROP is limited and variable. Even if retinal surgery appropriately repositions the detached retina, recovery of the patients'visual function remains limited. Therefore, early screening and an appropriate treatment for early ROP is vital to reduce the rate of blindness in low birth weight and premature infants. In2004, the ministry of health has issued "the premature treatment with oxygen and retinopathy prevention guide". Since then, many screening results from big hospitals (Level of Class III and Grade A) have been reported in China, but there is no reports from basic-level hospitals. So, we screened the retina of premature and low birth weight babies in the panyu district at Guangzhou with binocular indirect ophthalmoscope which incorporated with a video recordingsystem.
The key of standardization of ROP screening is to set a reasonable and unified screening standard. There are more or less differences between the ROP screening standards around the world. In general, the screening standard of a country or region was set on the basis of the risk factors and the analysis of recognized results at local city. The ROP screening standard of China was put forward by the Chinese Medical Association in2004in the guideline "Guide and treatment for premature infants with oxygen and ROP prevention ". This standard is as the following:Ocular fundus screening for premature and low birth weight (less than2.0kg) infants, and the follow-up should be continued until the peripheral retinal becomes neovascularization. It is appropriate to expand the scope of ROP screening in those infants with serious disease. But Li Xiaoxin said that the screening standard of our country is inadequate on the basis of lack of enough time number of reliable epidemiological data. So we need continue to conduct relevant research, along with reasonable use of oxygen after ROP onset in the circumstance of a continuous correction nt the characteristics of ROP in our country.
The ROP screening started late in China, and mainly concentrated in the large hospitals of developed areas. It is not well completed in most of Grade III hospitals, rather than the maternal and child health hospitals at the level of Grade II and the lower. Because the different object of ROP screening in various medical institutions of different regions and the different incidence rate among respective reports, it is difficult to evaluate the epidemiological characteristics of ROP in China. Treatment of premature infants in hospitals of Grade III is very difficult to be done due to far distance and high cost. Therefore, we should pay more attention to the screening of retinopathy of prematurity in the hospitals of grade two and below. The screening object, standard tool, its training and data analysis in all levels of hospital should be unified, in order to achieve a satisfactory epidemiological study. The accurate incidence, correct risk evaluation of ROP and the most appropriate screening criteria can be achieved based only on the reliable epidemiological research.
In this study, binocular indirect ophthalmoscope with video was used for retinal screening of premature and low birth weight infants in the Panyu District of Guangzhou city. The results were analyzed in order to understand retina development of premature infants and the occurrence of retinopathy in Grade II hospitals and find a suitable method and a standard for screening retinopathy of prematurity at primary hospitals in our country, and to provide epidemiological data for multicenter study on retinopathy of prematurity screening in our country. To our knowledge, this study is the first report on retinopathy of prematurity screening amnong the grass-roots hospitals in China. The screening model will be a good reference for ROP screening in the other Grade II hospitals. The screening results of the premature infants are of great significance for preventive research and epidemiological screening in China.
Objective
To investigate the characteristics of the retinal development of premature infants in the secondary hospitals in China. To explore a suitable ROP screening method and standard for hospitals of basic level in China in order to provide epidemiological data for multicenter study on ROP screening.
Methods
This prospective study enrolled1270premature infants for ROP screening. The procedures were examined by using a computer-assisted imaging system of binocular indirect ophthaimoscope. The development of retina was observed and the fundus lesions were recorded and compared with other basic level hospitals in China. The relationship of birth weight, gestational age at birth or the number of embryos and the occurrence of ROP was analysed by chi-square test with SPSS software. It is regarded as statistically significance if the p value of difference is less than0.05.
Results
1. Normal performance of premature retina:
Except the14cases with ROP patients,5cases had vitreous lesions,32cases had retinal hemorrhage,2cases had optic neuropathy patients. According to the research group, the corrected gestational age of1217cases with normal fundus is divided into32-36weeks,37-40weeks,41-46weeks, and greater than46weeks.There were133,603,388, and603premature infants in each group respectively. OPTIC CUPThe retinal developmentsuch as retinal vascularization and macular development is as follows:
(1) the morphology of optic cup:In the1217normal infants, the optic cups od1016cases of premature infants (83.5%) showed waned, light color, unclear borders, optic cup is not obvious;. The optic cups of201cases are reddish, with clear border. The optic cup is not obvious.
(2) Macular morphology:In the32-36weeks group with133cases of premature infants, the macular contour of105cases is not obvious, accounted for78.0%.14cases had clear macular outline (10.0%). The macular halo was ambiguously seen, the macular fovea did not see. The color of macular and peripheral retina did not change. In the37-40weeks group with603cases of premature infants, macular outline is obvious in587cases of premature infant, accounted for97.3%; macular anti halation is clearly visible in575cases, accounted for95.3%. In the41-46weeks group with388cases of premature infants, macular morphology changes obviously in352cases (90.7%),, the central part of retinal fovea presented obvious flake dark red or reddish brown, and formed a certain degree of sag with slope shape. A concave shape of macular center formed, without macular fovea reflex. In the greater than46weeks group with93cases of premature infants, macular fovea formation with visible foveal reflex presented in78cases (83.9%).
(3) The morphological change of retinal vascularization:In the32-36weeks group with133cases, the pole of retina behind nasal side arteriovenous vascular branches were obvious in81cases (60.9%). In these cases, the blood vessels and the stripes were clear, the nasal side of retina started to show secondary branch blood vessels,. Thesurrounding retina was not completely vascularized. The retina of temporal side was completely vascularized in133cases (100%),. In the37-40weeks group with603cases of premature infants, premature retina at nasal lateral was completely vascularized in467cases (77.4%).;237(50.7%) cases of premature infants presented obviousarteriovenous branches after the pole of the temporal retina. The blood vessels and the stripes are clear, the temporal range with retinal vascularization reached its temporal retina II area. The temporal retinal blood vessels have serrated edge in187cases (40.4%), vascularization reached III area. In the41-46weeks group with388cases of premature infants, the retina at nasal side has completely retinal vascularization in388cases (100%). The secondary retinal blood vessels surrounding the nasal side stripe are still clearly visible. The peripheral blood vessels near serrated edge and distal retina did not present cloudy. The lateral temporal retina was vascularized from areaⅢ to the temporal side in357cases (92%). In the greater than46weeks group,93cases (100%) had completely vascularized premature nasal lateral temporal retina.
(4)The types of retina pigment:Among the1217normal cases,901cases (71%) had retinal darker and pewter.278cases (21.8%) had mild leopard shaped fundus change. For the choroid type,91cases (7.2%) had lighter color sclera. The premature fundus can be seen in876cases (72%), after long ciliary nerve.
2. The occurrence of dfundus disease:
(1)ROP:In the study of1270cases,14cases of children had ROP. The lesions subsided in12cases during follow-up, The lesions subsided in2cases after laser treatment.
(2) retinal hemorrhage:In the1217normal cases,32cases had varied degrees of retinal hemorrhage.20cases were monocular,12cases were binocular.22cases of retina had small bleeder,6cases of retina had large focal hemorrhage,4cases had a few small bleeder in the pole.32cases were natural birth child. The weight of1case of ROP children was greater than2450g.4cases had a history of forceps. The bleeding was completely absorbed in27cases after4weeks follow-up. The retina is still visible traces in5cases.
(3) Vitreous lesions:In the1217normal cases,5cases had vitreous lesions.1case was confirmed as residual vitreous artery;1case was observed with a white eye glance, which was confirmed by color doppler ultrasound and CT examination for permanence original vitreous hyperplasia.2twins had vitreous hemorrhage. For very low birth weight, temperature box feeding, and doubt ROP, the infants were recommended to a higher level hospital to make a diagnosis and give treatment. Those infants due to poor general condition and family economic difficulties, their parents refused to transfer them to a better treatment and then missed follow-up.1case had large clumps gray haze in the vitreous, retinal structure is not clear, was suggested to turn to the next higher level hospitals for further examination, after the diagnosis of retinoblastoma.
(4) Optic neuropathy:In1217normal infants, examination showed apparent papilla edema in2cases, neonatal hypoxic ischemic encephalopathy in1cases.1case was confirmed as intracranial pressure.
3. Complications:Before and after the inspection process,35cases occurred with different degrees of ball subconjunctival hemorrhage. The incidence was2.76%, and natural faded after2weeks follow-up.2cases had massive haemorrhage under the scalp. The incidence is0.16%and was natural faded after1week follow-up.1case had acute conjunctivitis and was treated with tobramycin eyedrops and eye ointment for3days. The rate is0.08%, and was healed in1week.28cases underwent screening and often exclaimed. The incidence was2.2%, and the symptoms disappeared in around1week. Serious complications such as apneaand shock have not been found.
4. ROP:According to the screening criteria of Guangzhou city,14cases had ROP. If according to the screening standard set by the ministry of health,13cases had ROP. Among them,7cases is in III area I period;3cases is in III area Ⅱ period,2cases is in III area III period,2casesis in II area III period. No cases were found in stage IV and V lesions.2cases with threshold lesions needed treatment.
5. Birth weight, gestational age, and their relationships with ROP
In the14cases of ROP,11cases birth weighed from1000to1500g, accounted for21.1%of the total52cases, accounting for78.6%of the total number of ROP (11/14).2cases weighed from1501to2000g, accounting for1.01%of the182cases total, accounting for14.3%of the total number of ROP (2/14).1case weighed among2001-2500g, accounting for0.1%of the688cases total, accounting for7.1%of the total number of ROP (1/14). No premature illness was found whenthe birth weight was greater than2500g (x2=201.431, P=0.000<0.05), suggesting that the smaller the birth weigh, a higher ROP rate. The difference is statistically significant.
In the14cases with ROP,11cases were born in27to32weeks of gestational age, accounting for10%of110total cases.2cases was33-34weeks gestational age, accounting for0.96%of the207total cases.1case was35to37weeks gestational age at birth, accounting for0.1%of the793total cases. No birth gestational age greater than37weeks was noted with premature illness(x2=88.63, P=0.000<0.05), suggesting that smaller the gestational age, higher the ROP rateat birth. The difference is statistically significant.
In the14cases of ROP,10cases were singleton, saccounting for0.82%of the total cases1225cases of premature infants. There are4twins, accounting for8.9%of the total of45twins (x2=28.486, P=0.001<0.05), suggesting that the incidence of ROP in twins is higher than singletons. The difference is statistically significant.
6. Comparison of the incidence of ROP between different screening standards
According to Guangzhou screening criteria (<37weeks premature birth or birth weight2500g), the prevalence of ROP in low birth-weight infants was1.1%(14/1270). According to screening standard issued by Chinese ministry of health, the incidence was5.56%(13/234). If according to this standard screening,2cases with III area III ROP were missed. Children will have less screening,1036cases were tested5times. According to the screening criteria (<2000g birth weight or gestational age<28weeks premature babies), incidence of ROP is21.1%(11/52).According to this standard by the ministry of health,1case with II period III area ROP was missed., The amount of infant with ROP will reduce182cases, equivalent to21.1%of examined children.
7. Comparion with other domestic tertiary hospitals on the incidence and screening object
In recent years, the incidence of premature infants reported by the tertiary hospitals variable in our country. The incidence of premature infants in Shanghai is6.6%, the rest is from10%to-20%. Screening tool in Xi'an city was the RetCam. The rest used the binocular indirect ophthalmoscope. RetCam as a complementary and binocular indirect ophthalmoscope at the same time was used Hubei and shenzhen. The object of screening was different:Beijing and Shanghai is a children's hospital, maternal and child health care or comprehensive hospital inpatient children with neonatal unit. In xi'an and Hubei general hospital, the object is pediatric inpatient and ophthalmic outpatient children.The object is a children's hospital inpatient and ophthalmic outpatient children in Hunan and Guangzhou. It is the maternity and child care hospital and an eye clinic in Guangdong. Children in shenzhen were from comprehensive hospitals, health care of women and children, the inpatients of ophthalmology and eye hospital outpatient service. The birth weight for screening object ranged from500-3500g. The difference of birth weight is large. The birth weight at Guangzhou children's hospital was1256.2+/-268.1g;1487.3+/-276.15g a Shangha;1771.5+/-362.7g at Beijing, and1722.2+/-363.8g at Xi 'an,1650g atGuangdong Shenzhen,1972.2+478.3g at Hubei. Birth gestational age ranged from24to38.86weeks. The average gestational age at birth was32weeks.
Conclusion
1. Premature fundus, have different characteristics according to the growth of the age due to its amature development of anatomical structure. Most retinas of ROP retard development than normal preterm infants. Most OPTIC CUPfundus are not round with mild color and unclear cup rims. The retinal veins of the posterior retina showed stripe type and visible branch. The macular halo is obvious with intense reflection, its range is big. Most macular foveas are not obvious.
2. Preterm infants usually had some special lesions in the fundus due to abnormal embryonic development, the production process and the maternal disease.. Premature retinopathy, retinal hemorrhage, vitreous artery residual, persistent primary vitreous hyperplasia, papillary edema are very commonly appeared. Retinopathy of prematurity (ROP) is a kind of retinal vascular proliferative lesions happens in premature and low birth weight babie. It is based on immature retinal disease. Its pathogenesis is unclear. There are many theoriesexplain the formation of ROP as free oxygen radicals theory,cytokine and spindle cells theories. The etiology of ROP was unknown. Premature birth and low birth weight have been recognized as the cause of ROP. Low birth weight is the major cause of ROP. Lower the birth weight, higher the incidence of ROP. Lesser the birth gestational age, higher the incidence of ROP. If give late operation for ROP, visual function has not significant improvement in children. The pharmaceutical prevention and its early intervention for premature retinopathy have been in investigation for years. There is no currently effective drug for controlling ROP occurrence and development. Therefore, early screening is the only effective way to prevent blindness due to ROP.
3. Our results showed that the digital binocular indirect ophthalmoscope system can reliably and directly provide clear digital images and videos of the peripheral retina. This system has several advantages. It provides accurate high-quality images. It is affordable, and it remains the advantages of the "gold standard" binocular indirect ophthalmoscope. Because of its low price, it is suitable for screening ROP in all small hospitals, especially primary hospitals in China.
4. The compound tropicamide eye drops did not show obvious complications for mydriatic inspection in premature babies. The on-table examination with binocular indirect ophthalmoscope is safe for premature retina in infanst. But for reducing the fear of parents and children and the testing time, we suggest a skilled, special trained and gentle doctor.
5. The screening standard set by the ministry of health in China works well for ROP screening in the Panyu district at present. It still needs further research of large sample to decide whether the minimal weight of infant for enrollment should reduce to1500g. The study period is short, the sample size is relatively small. In the later work, we will continue to increase the sample size in accordance with the standards set by the ministry of health screening, in order to investigate the best suitable threshold of screening criteria in for different regional hospital in China.
6. Due to different objective of ROP screening in various areas and various medical institutions, the incidence is also variable. It is difficult to assess the epidemiological characteristics of ROP. A uniform screening object and screening tool has to be needs or unified training and analysis of all data in all levels of hospital for epidemiological studies. Because of far distance and high cost, it's easy to miss the follow-up in tertiary hospital. Therefore, we should focus ROP screening work on the secondary and even lower hospitals. As far as we know, this is the first study on ROP screening in the basic-level hospitals (second class hospital). The screening model for other secondary hospitals in our country to carry out the ROP screening work will have a very good model function. The results of retina screening, its prevention and epidemiology research for premature infants in China has great significance.
引文
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