阈值期早产儿视网膜病变的临床特征及治疗效果分析

目的 分析阈值期早产儿视网膜病变(ROP)的临床特征,并评价眼底激光凝固术的治疗效果.方法 对549例符合筛查指征的早产儿进行眼底筛查,共发现ROP患儿108例,1、2期及3期非阈值病变ROP患儿74例,阈值病变ROP患儿34例;对阈值病变ROP患儿进行眼底激光凝固术治疗,术后眼科医师定期检查眼底.结果 ROP总发生率为8.6%(108/1255),占筛查数的19.7%(108/549),阈值病变ROP占早产儿的2.7%(34/1255),占筛查数的6.2%(34/549).1、2期及3期非阈值病变ROP患儿的胎龄、出生体重均较阈值病变ROP患儿大,而吸氧时间较短,差异均有统计学意义(P<0.05);74例1、2期及3期非阈值病变患儿未治疗,定期随访至眼底恢复正常.34例阈值病变ROP患儿的68只眼接受眼底激光凝固术治疗,成功率为94.1%,2例(4只眼)治疗后发生部分视网膜脱离,经玻璃体视网膜手术后病变控制.结论 早产儿胎龄越小、出生体重越低、吸氧时间越长,ROP阈值病变的发生率越高;预防的关键是早期筛查;眼底激光凝固术治疗是阻止阈值期ROP发展的有效方法;术后处理重点是呼吸管理.     

早产儿视网膜病筛查及高危因素分析与随访

目的研究早产儿视网膜病（retinopathy of prematurity，ROP）的发生率、高危因素、治疗及预后。方法对2002年8月至2003年2月间收住北京妇产医院新生儿重症监护病房胎龄≤35周且出生体重≤2500g的74例早产儿于生后35周进行眼底检查，诊断ROP者2～3周随访一次，ROP病变发展到阈值及以上者手术治疗，其中56例早产儿于2～3岁时行眼瞬息图象筛分仪筛查视功能。结果检出ROP患儿11例，包括Ⅰ期4例，Ⅱ期4例，Ⅲ期3例，发生率为14．9％。其中Ⅰ、Ⅱ期病变均恢复正常；3例Ⅲ期阈值患儿给予手术治疗。ROP高危因素分别为早产、低出生体重和氧疗。56例早产儿在2～3岁时发现屈光不正26例，斜视8例，白内障1例。结论ROP在早产儿发生率较高，程度较重，对患儿远期视功能影响较大。建议对早产儿尤其是有高危因素的早产儿于生后4周左右常规进行眼科检查，并定期随访，以早发现、早治疗，改善ROP患儿预后，提高生命质量。     

早产儿视网膜病107例临床特点及预后分析

摘要：目的　评价早产儿视网膜病（ROP）临床特点及远期治疗效果。方法　回顾性分析2004-01-01—2009-07-31复旦大学附属儿科医院新生儿科收治的107例ROP患儿临床资料、ROP分期、治疗情况及远期预后。结果　1期和2期ROP共64例,6例2期病变达Ⅰ型阈值前病变而采用激光治疗,其他均未进行特殊治疗;除失访和死亡病例外,所有随访病例ROP病变均消退,远期视力不受影响。3期病变15例,其中14例达阈值病变者给予激光或冷凝治疗,1例未达阈值病变者不需要治疗。有完整随访资料的11例患儿中3例术后视力严重受损,仅存在光感,其余8例视力正常。4期和5期ROP共28例,随访的18例患儿中,仅1例手术后保存了正常视力（占5.6％）,失明者达12例（占66.7％）,其余5例虽保存视力,但视力极差,仅存光感（占27.7％）。结论　ROP防治关键在于预防ROP发生,当出现ROP早期病变时应严格筛查和及时干预,一旦疾病进入晚期,出现视网膜脱离时再治疗,则治疗效果不佳。     

间接检眼镜眼底成像技术支持下的早产儿视网膜病变筛查研究

目的 研究间接检眼镜眼底成像技术支持下的早产儿视网膜病变(ROP)筛查模式和特点.方法 采用双目间接检眼镜成像系统对250例早产儿进行ROP筛查.结果 250例早产儿检出ROP 23例,其中1期10例,2期5例,3期4例,急性后极部ROP 1例,5期3例.通过间接检眼镜成像技术,ROP 1期、2期、3期病变,附加病变等典型病变的特征图像均被捕获,并总结出正常早产儿和ROP患儿的眼底特征.结论 间接检眼镜成像技术支持下的ROP筛查模式能够清晰获取早产儿眼底图像,并准确记录ROP筛查结果.操作简单,可望成为ROP筛查项目开展的基础.     

2185例早产儿视网膜病变筛查结果及其高危因素

目的 了解早产儿视网膜病变(retinopathy of prematurity,ROP)发生率及高危因素.方法 2009年1月1日至2010年12月31日,采用RetCamⅡ数字视网膜照相机对入住北京军区总医院附属八一儿童医院新生儿重症监护病房的2185例胎龄≤34周或出生体重≤2000 g的早产儿进行眼底筛查,根据筛查结果分成ROP组和非ROP组,计算ROP的发生率,并采用单因素分析和Logistic回归分析探讨ROP的危险因素.结果 接受眼底筛查的2185例早产儿中,共发生ROP287例,发生率为13.1％.按国际ROP分类标准,Ⅰ区病变34例、Ⅱ区病变147例、Ⅲ区病变106例,分别占11.9％、51.2％和36.9％.1、2、3期病变分别为11 7例、142例和28例,分别占40.8％、49.5％和9.7％,未发现4、5期病变.其中36例患儿发现附加病变,占12.5％.Logistic回归分析显示,胎龄小(OR=0.859,95％ CI:0.770～0.958,P=0.006)、出生体重低(OR=0.729,95％CI:0.634～0.838,P=0.000)、吸氧时间长(OR=2.221,95％CI:1.904～2.592,P=0.000)、辅助通气(OR=3.104,95％ CI:2.096～4.956,P=0.000)、呼吸暂停(OR=1.767,95％ CI:1.103～2.831,P=0.018)和贫血(OR=2.242,95％CI:1.641～3.604,P=0.000)是早产儿发生ROP的独立危险因素.结论 早产儿ROP发生率较高,低胎龄、低出生体重、吸氧时间长、辅助通气、呼吸暂停和贫血是其主要危险因素,临床上应针对以上因素采取相关措施,从而降低ROP发生率.     

早产儿视网膜病多中心筛查及发病率调查

目的 多中心调查国内早产儿视网膜病（retinopathy of prematurity，ROP）发病情况，建立ROP筛查制度。方法 建立由11家医院参加的多中心筛查协作网，对2005年1月1日至12月31日在合作单位出生或收治的出生体重＜2000g的低出生体重儿进行ROP筛查。结果 在完成随访的621例研究对象中73例发生ROP，发病率为11．8％；出生体重在1500-1999g者25例发生ROP，发生率为5．9％；出生体重在1000-1499g者45例发生ROP，发生率为23．6％；出生体重〈1000g者3例发生ROP，发生率为60．0％。发生1期ROP24例，2期ROP35例，3期及以上ROP14例；激光治疗16例，冷冻术8例，玻璃体切除术1例，无失明病例。结论 出生体重〈2000g的早产儿ROP发生率为11．8％，筛查能使ROP得到早期诊断和治疗，降低ROP的危害，可在全国范围推广。     

早产儿视网膜病变的发病机制和治疗进展

早产儿视网膜病（retinopathy of prernaturity，ROP）以往称之为晶状体后纤维增生症（retrolental fibroplasia）。1942年由Terryr首先报道，本病的显著特点是晶状体后有白色纤维组织增生，故得此名。1984年被正式命名为早产儿视网膜病（ROP）。ROP是视网膜血管发育异常的双侧眼病，表现为视网膜缺血、新生血管形成、增生性视网膜病变，最后导致视网膜瘢痕、玻璃体出血、甚至视网膜脱离。     

重组人类基因促红细胞生成素对早产儿视网膜病变影响的分析

目的　探讨重组人类基因促红细胞生成素（rhu-EPO）的应用对早产儿视网膜病变（ROP）的影响。方法 　对2005年3月至2008年6月期间收住福建医科大学附属漳州市医院新生儿科的早产儿（体重 ≤ 1500 g）病例资料进行分析，应用rhu-EPO治疗的94例为治疗组，未应用rhu-EPO的65例为对照组，生后6周或纠正胎龄35周时行眼底检查，根据ROP国际分期标准进行ROP诊断和分期，同时对多种相关因素进行统计分析。结果　治疗组严重ROP的患病率高于对照组（P < 0.05）；单因素分析显示rhu-EPO治疗 ≥ 10剂，发生严重ROP的风险高于rhu-EPO治疗剂数<10剂（r = 6.429，P < 0.001），开始治疗时间 ≥ 14 d发生严重ROP风险明显高于 < 14 d（ r =46.000，P < 0.001）；多因素Logistic分析显示rhu-EPO治疗剂数 ≥ 10剂发生严重ROP风险高（r = 9.348，P < 0.001）。结论　应用rhu-EPO是早产儿ROP的一个独立危险因素。     

糖尿病合并妊娠伴视网膜病变孕妇的临床观察

目的：研究糖尿病合并妊娠伴视网膜病变孕妇的妊娠结局及孕期视网膜病变。方法：回顾性分析１９８１～１９９５年间４９例糖尿病孕妇妊娠情况。伴视网膜病变的１６例分为第Ⅰ组；无视网膜病变的３３例分为第Ⅱ组。第Ⅰ组糖尿病病程平均为８．９２±４．３５年；第Ⅱ组为３．１１±１．７４年。结果：第Ⅰ组孕妇并发症及围产儿发病率较高，但两组比较，差异无显著性（Ｐ＞０．０５）。３１．１％孕妇视网膜病变在孕期加重，但仍属单纯型（背景期）。结论：糖尿病合并妊娠伴眼底病变时，仍可以继续妊娠，但孕期应密切观察眼底变化和严格控制血糖。     

高氧诱导新生鼠视网膜病变的实验研究

目的　建立早产儿视网膜病 (retinopathyofprematurity ,ROP)的动物模型 ,为研究发病机制及治疗提供实验基础。　方法　选择 7日龄新生小鼠 5 4只 ,分为实验组和对照组。实验组 2 7只 ,在氧浓度为 75 %的密闭容器中生长 5d ,然后回到正常空气中 ;对照组 2 7只 ,吸室内空气。观察两组视网膜病变 ,视网膜铺片经ADP酶染色 ,以了解视网膜血管的改变 ;视网膜切片经常规HE染色 ,计数突破视网膜内界膜的血管内皮细胞核数目 ,以定量反映视网膜血管的增生情况。　结果　实验组新生鼠在高氧中生长 5d后 ,视网膜血管明显收缩、阻塞 ,视网膜大片区域无灌注 ;回到正常空气中 2d后 ,新生血管开始形成 ;回到空气中 5d后 (生后第 17天 ) ,新生血管形成达到高峰。实验组小鼠生后第 17天时突破视网膜内界膜的血管内皮细胞核数目达 4 4个 ,而对照组不足 2个 ,差异有非常显著性 (P <0 .0 0 0 1)。　结论　该动物模型视网膜病变与早产儿视网膜病变相似 ,制备过程简便 ,可重复性高 ,并可进行定量研究 ,是研究ROP发病机制及治疗对策较合适的模型。     

Pregnancy disorders appear to modify the risk for retinopathy of prematurity associated with neonatal hyperoxemia and bacteremia

Abstract

Objective: To explore (1) whether extremely low gestational age newborns exposed to inflammation-associated pregnancy disorders differ in retinopathy of prematurity (ROP) risk from infants exposed to placenta dysfunction-associated disorders, and (2) whether ROP risk associated with postnatal hyperoxemia and bacteremia differs among infants exposed to these disorders.

Methods: Pregnancy disorders resulting in preterm birth include inflammation-associated: preterm labor, prelabor premature rupture of membranes (pPROM), cervical insufficiency, and abruption and placenta dysfunction-associated: preeclampsia and fetal indication. The risk of severe ROP associated with pregnancy disorders was evaluated by multivariable analyses in strata defined by potential effect modifiers, postnatal hyperoxemia and bacteremia.

Results: Compared to preterm labor, infants delivered after pPROM were at reduced risk of plus disease (Odds ratio?=?0.4, 95% confidence interval: 0.2–0.8) and prethreshold/threshold ROP (0.5, 0.3–0.8). Infants delivered after abruption had reduced risk of zone I ROP (0.2, 0.1–0.8) and prethreshold/threshold ROP (0.3, 0.1–0.7). In stratified analyses, infants born after placenta dysfunction had higher risks of severe ROP associated with subsequent postnatal hyperoxemia and bacteremia than infants born after inflammation-associated pregnancy disorders.

Conclusion: Infants exposed to placenta dysfunction have an increased risk of severe ROP following postnatal hyperoxemia and bacteremia compared to infants exposed to inflammation-associated pregnancy disorders.     

Intravitreal bevacizumab for retinopathy of prematurity as first line or rescue therapy with focal laser treatment. A case series

Objectives: Laser therapy is effective in the treatment of severe forms of retinopathy of prematurity (ROP), and aggressive posterior ROP (APROP), but always damages the retina. We report our preliminary findings in seven premature infants with complicated ROP or APROP who were treated with intravitreal bevacizumab (IVB) as first line monotherapy or rescue therapy combined with laser treatment. Methods: We studied retrospectively seven preterm infants, who were affected by APROP (n = 4) or pre-threshold ROP (n = 3). Infants were treated with IVB (0.625 mg; Avastin®, Roche, Basel, Switzerland) monotherapy (n = 2) when they were too sick to undergo lengthy laser treatment. Results: Monotherapy IVB (n = 3 eyes) and IVB combined with laser therapy (n = 3 eyes) of APROP cases were followed by regression of the ROP and complete peripheral vascularization. The combined therapy with IVB and laser therapy of pre-threshold ROP (5 eyes) produced a regression of neovascularization and good retinal anatomical outcome. Conclusions: In our series, IVB was successful in treating ROP in a small cohort of extremely preterm infants with APROP or pre-threshold ROP, both as monotherapy or rescue treatment after laser therapy, without the development of ocular and systemic short- and long-term adverse effects.     

Arterial oxygen fluctuation and retinopathy of prematurity in very-low-birth-weight infants.

OBJECTIVE: To determine the influence of arterial oxygen fluctuation on development of threshold ROP. STUDY DESIGN: Retrospective study of 231 infants, < or =1500 g birth weight, who were admitted to Arkansas Children's Hospital NICU from January 1993 to June 1995. Fluctuation in partial pressure of dissolved arterial oxygen (PaO(2)) was expressed as coefficient of variation (CoV) for each infant. We investigated the relationship between CoV at three intervals and the risk of developing threshold ROP. RESULTS: The odds ratio (OR) of developing threshold ROP versus prethreshold ROP or less associated with a 10% increase in the CoV during the first 5 days of oxygen therapy was 1.44, and during the first 10 days was 1.51. When analysis was restricted to infants receiving 30 days of therapy, the OR during the first 5 days of therapy was 1.67, during the first 10 days was 1.82, and during days 11-30 was 1.68. CONCLUSIONS: Very-low-birth-weight infants experiencing fluctuating PaO(2) are at higher risk of threshold ROP.     

Cumulative illness severity and progression from moderate to severe retinopathy of prematurity.

OBJECTIVE: To test cumulative neonatal illness severity (IS) and IS fluctuation as predictors of progression from moderate to severe retinopathy of prematurity (ROP). METHODS: Data from research databases and medical record review were collected for infants from four neonatal intensive care unit (NICUs) admitted between 1995 and 2001 and diagnosed with prethreshold ROP. Cumulative neonatal IS measured using daily Scores for Neonatal Acute Physiology (SNAP) for the first 28 days of life, and IS fluctuation as assessed by summing changes between daily SNAP scores, were tested as predictors of progression to threshold ROP using logistic regression. RESULTS: Infants progressing to threshold (n=79), compared to those not progressing to threshold (n=130), had significantly (P<0.05) lower gestational ages (25.2+/-1.1 versus 25.8+/-1.4 weeks), higher cumulative neonatal SNAP (255+/-77 versus 224+/-63 weeks) and had more severe hospitalizations as indicated by diagnoses and medical management. In regression analysis, gestational age, chronological age and presence of plus disease at first diagnosis of prethreshold were associated with development of threshold. After adjusting for these factors, cumulative neonatal SNAP was significantly associated with progression to threshold. However, addition of cumulative SNAP to the model only increased receiver-operating characteristic curve area from 0.77 to 0.78 (NS). Other factors, including SNAP fluctuation, were not associated with progression to threshold after adjustment using this model. CONCLUSIONS: Cumulative neonatal IS, as measured by cumulative SNAP, is an independent risk factor for progression from moderate to severe ROP. However, cumulative IS does not enhance assessment of risk for ROP progression after adjusting for simpler clinical factors.     

Understanding retinopathy of prematurity: update on pathogenesis

Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex condition in which various factors participate at different stages of the disease leading to microvascular degeneration followed by neovascularization, which in turn predisposes to retinal detachment. Current ablative therapies (cryotherapy and laser photocoagulation) used in the clinic for the treatment of ROP have limitations and patients can still have long-term effects even after successful treatment. New treatment modalities are still emerging. The most promising are the therapies directed against VEGF; more recently the use of preventive dietary supplementation with ω-3 polyunsaturated fatty acid may also be promising. Other than pharmacologic and nutritional approaches, cell-based strategies for vascular repair are likely to arise from advances in regenerative medicine using stem cells. In addition to all of these, a greater understanding of other factors involved in regulating pathologic retinal angiogenesis continues to emerge, suggesting potential targets for therapeutic approaches. This review summarizes an update on the current state of knowledge on ROP from our and other laboratories, with particular focus on the role of nitro-oxidative stress and notably trans-arachidonic acids in microvascular degeneration, semaphorin 3 operating as vasorepulsive molecules in the avascular hypoxic retina and in turn impairing revascularization, succinate and its receptor GPR91 in neuron-mediated retinal neovascularization, and ω-3 lipids as modulators of preretinal neovascularization.     

Retinopathy of prematurity in larger preterm infants

Severe retinopathy of prematurity (ROP) usually occurs in preterm infants with birthweight<1500 g or gestational age<31 weeks. However, some exceptions occur in larger preterm infants. In southern Taiwan, six larger preterm infants with gestational age older than 31 weeks and birthweight>1500 g had stage III ROP in Chang Gung Memorial Hospital at Kaohsiung (Taiwan, Republic of China). All six infants were male and had received oxygen supplementation during hospitalization. Only one infant had received previous surgery and frequent packed red blood cell transfusions. Three infants received laser photocoagulation or cryotherapy, and all infants have good outcomes regardless of whether they received treatment. This report provides convincing evidence for expanding the screening criteria in our nursery and emphasizes the importance of assessing the risk of ROP for larger preterm infants.     

Association of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy of prematurity and progression to laser therapy in extremely low-birth-weight infants.

OBJECTIVE: The objective of this study was to evaluate the role of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy and progression to laser therapy. BACKGROUND: Postnatal steroids have been frequently used in the management of infants with chronic lung disease, airway edema, and hypotension, but their use is not free from adverse effects. Postnatal dexamethasone use has been associated with increased risk for the development of fungal sepsis, but the influence of glucocorticoid therapy on retinopathy of prematurity (ROP) is controversial. Candida sepsis has been shown to be associated with severe ROP and the need for laser therapy in some studies but not in others. STUDY DESIGN: Medical records of all <1000 g birth weight infants (n=158) admitted to Louisiana State University Health Sciences Center between July 1, 1996 and June 30, 1999 were reviewed. After exclusion of those infants who either died (n=25) or transferred (n=3) before eye examination, demographic and clinical data of 130 infants were analyzed by chi-squared analysis, Mann-Whitney U test, t-test, analysis of variance, and logistic regression. All data are mean+/-SD. RESULTS: Gestational age was 26.4+/-1.7 weeks; birth weight was 797+/-130 g. Twenty-six infants were Caucasian, the rest African-American. Seventy-five (58%) received antenatal steroids. Eighty-eight (68%) of the infants received postnatal steroids. All infants were exclusively fed premature infant formulae. Sepsis developed in 44 (34%) infants and fungal sepsis in 14 (11%). Incidence of ROP was 77% (100/130), severe ROP (stage > or =3) 52% (68). Severe ROP was more frequent in Caucasian infants (p=0.005) and in infants who received postnatal dexamethasone (p< or =0.0001). The development of threshold ROP (zone 1 or 2 with stage 3+, five contiguous or eight total clock hours of the retina) and requirement for laser therapy were higher in Caucasians (p=0.0002) and in infants with fungal sepsis (p=0.001). Antenatal steroids had no effect on the severity of ROP or the need for laser treatment. Postnatal dexamethasone use was significantly associated with fungal sepsis 13/14 (93%). After controlling for gestational age, race, days on supplemental oxygen, and fungal sepsis, cumulative postnatal dexamethasone use was independently associated with severe ROP [OR 1.2 (1.04-1.33)], and fungal sepsis [OR 8.2 (2.0-33.0)] was independently associated with the need for laser therapy. CONCLUSIONS: Postnatal steroid use is an independent risk factor for development of severe ROP. The risk of threshold ROP requiring laser treatment was higher in infants who developed fungal sepsis.     

Cryotherapy for threshold retinopathy: perioperative management in a single center

Perioperative management and complications during and after surgery were reviewed in a population of premature infants who received cryotherapy because of threshold retinopathy by retrospective analysis of medical, anaesthetic, and ophthalmologic files. Infants (n=31) who received cryotherapy between January 1, 1996 and January 1, 2001 and were treated during the neonatal period in the unit were included in the study. Cryotherapy was performed under general anesthesia on the neonatal ward. Neonatal and preoperative characteristics of this cohort point to a vulnerable group of infants with a preoperative weight of 1622 g (1519 to 1862 g), bronchopulmonary dysplasia criteria applying in 29 of 31 patients and methylxanthins prescribed in 26 of 31 patients. No single cryotherapy session had to be interrupted because of systemic complications. Still marked cardiorespiratory instability was documented until 36 hours postoperative in 8 patients. Performing surgical procedures on the neonatal ward is a feasible option. Perioperative management in infants who received cryotherapy is used as an illustration of this approach.