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.     

An Update on Retinopathy of Prematurity (ROP)

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the retina of premature infants. The clinical spectrum of ROP varies from spontaneous regression to bilateral retinal detachment and total blindness. Between these two extremes lies the form of ROP, which is amenable to treatment with laser photocoagulation, anti-vascular endothelial growth factor drugs or surgery. Increasing rates of preterm births coupled with better survival rates but lack of uniform quality of neonatal care and delays in diagnosis have led to increasing ROP blindness. Atypical forms of Aggressive Posterior ROP are seen in heavier birth weight babies in developing countries. Prevention of ROP by following stringent protocols for supplemental oxygen, prevention of sepsis, timely screening and laser treatment by a concerted and collaborative effort of neonatologists and ophthalmologists are required to fight the blindness from ROP.     

Retinopathy of prematurity: the disease process, classifications, screening, treatment, and outcomes

Retinopathy of prematurity (ROP) is the cessation of normal eye development and subsequent abnormal vessel growth that occurs exclusively in premature infants. ROP was first discovered in the 1940s and was for two decades the leading cause of blindness in children. Currently, the disease causes about 500 new cases of blindness per year. The severity of the disease increases with decreasing gestational age. The pathogenesis of ROP involves disruption of normal retinal vascularization. Vessel endothelial growth factor, insulin-like growth factor, and oxygen play important roles in its development. ROP is classified using an international classification system that provides direction for screening and treatment of premature infants. Examinations are performed by ophthalmologists, who identify the scope of vascularization, the degree of abnormal vessel growth, and the amount of the eye that is affected. Treatment modalities include cryosurgery and laser photocoagulation. Long-term outcomes include both structural and functional vision problems.     

Retinopathy of Prematurity

Retinopathy of prematurity (ROP) occurs due to abnormal proliferation of retinal vessels. The most important risk factors which predispose to development of ROP include oxygen therapy, anemia needing blood transfusion, sepsis and apnea. Very low birth weight neonates, those born at ≤32 week of gestation and other preterm neonates with risk factors must be screened for ROP. As a general rule first screening should be done at 1 month of postnatal age. If screening detects ROP not needing treatment follow up should be planned according to location and stage of ROP. Better visual outcomes are observed with earlier treatment at lower threshold. Peripheral retinal ablation with diode laser under adequate analgesia and sedation is the preferred method for treatment of severe ROP. Guidelines regarding the procedure of dilatation, ophthalmic examination and treatment (if required) have been provided in the protocol. Close co-operation between the ophthalmologist and neonatologist is essential for successful management of ROP.     

Mediators involved in retinopathy of prematurity and emerging therapeutic targets

Retinopathy of prematurity (ROP) is a potentially blinding disease of premature infants and despite timely treatment some infants develop retinal detachment and sight loss. Current treatment utilises laser therapy which causes destruction of treated retinal tissue resulting in field loss. There is considerable research work ongoing on neovascular eye disease which is likely to result in antiangiogenic approaches that will arrest the development of ROP by specifically targeting the involved molecular mediators. Some of these new therapeutic interventions have entered clinical trials. This article reviews new information available on the molecular pathogenesis of ROP which may result in novel treatments for ROP; it does not discuss the well-known role of oxygen in the development of ROP.     

UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome

BACKGROUND: Retinopathy of prematurity (ROP) is one of the few causes of childhood blindness in which severe vision impairment is largely preventable. Ophthalmic screening for ROP is required to identify disease that requires treatment whereby the development of potentially blinding disease can be minimised. OBJECTIVES: To make the first UK population based estimate of the incidence of babies with severe ROP (stage 3 or more); to document their clinical characteristics and management and to evaluate the appropriateness of current ROP screening guidelines in the UK. PATIENTS: Cases were recruited through a national surveillance programme with 1 year ophthalmic follow up and data from clinician completed questionnaires. RESULTS: Between 1 December 1997 and 31 March 1999, 233 preterm babies with stage 3 ROP were identified. Severity (location, extent, and presence of plus disease) was associated with degree of prematurity, most severe in the most premature babies. Fifty nine percent were treated. The UK screening protocol was followed in two thirds of cases, but in the remainder it was begun too late or was too infrequent. Three quarters of the cases were followed up at 1 year, and 13% had a severe vision deficit as a result of ROP. CONCLUSIONS: Visual deficit as a result of ROP in premature babies continues to be a severe disability in some of the survivors of neonatal intensive care. Further efforts are needed to organise treatment regionally to improve outcome and standards of practice.     

Retinopathy of prematurity: overview of new global problem

Retinopathy of prematurity (ROP) is a disease characterized by abnormal retinal vasculature in preterm infants. It is an important cause of visual disability in premature infants and although the incidence varies among different countries it is increasing as advances in neonatal care result in improved survival. Oxygen, growth factors like vascular endothelial growth factor, and poor postnatal growth play a significant role in the pathogenesis of ROP. Targeting lower oxygen saturation is associated with a reduction in ROP, but with increased mortality. Screening for ROP varies between centres and countries but generally it includes preterm infants (less than 32 weeks’ gestation) and/or those with a birth weight of less than 1500g. ROP has been recently reclassified as type-1-needing treatment and type-2 ROP needing observation, based on the benefits and treatment efficacy. Laser therapy and anti-VEGF are the two main treatments. Recent reports suggest that anti-VEGF therapy may have better visual outcomes (myopia) and a better safety profile. ROP is a global disease of prematurity and understanding the pathogenesis, course of ROP, preventive strategies, treatment options and outcomes are essential for all healthcare professionals caring for preterm babies. This short article describes the evidence for screening, prevention and treatment options and looks ahead to possible advances in the near future.     

Retinopathy of prematurity: recent advances in our understanding

Retinopathy of prematurity (ROP) has been recognised as an important cause of childhood visual impairment and blindness since the 1940s when improved facilities and treatment increased the survival rate of premature infants. Although its incidence and severity have been decreasing in developed countries over the past two decades, both are increasing in developing nations. ROP is consequently targeted as an important but avoidable disease. This review provides an updated summary and discussion of much of the work that has been produced through population, animal, cell culture, and genetic research. The authors examine the prevalence, risk factors, and possible causes of the disease with a particular focus on genetic studies. They conclude that while significant reductions in the disease have occurred in developed countries, further research is required to fully understand and prevent the disease. In the meantime, development and implementation of appropriate screening and treatment strategies will be critical in reducing blindness in developing countries.     

Human milk reduces the risk of retinal detachment in extremely low-birthweight infants

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of blindness in children. Because the use of oxygen is a known risk factor for development of ROP, supplemental oxygen is used carefully. However, it does not necessarily reduce the morbidity of ROP-induced blindness. The aim of the present study was to identify the possible risk factors for progression to retinal detachment, a most relevant cause of visual impairment, in extremely low-birthweight infants (ELBWI). METHODS: The medical records of the 42 ELBWI who were admitted to the neonatal intensive care unit in Asahikawa Kosei Hospital from April 1999 to March 2004 were retrospectively reviewed. Seven infants (16.7% of the ELBWI) developed retinal detachment and two of them became blind. Perinatal and postnatal variables in these infants with retinal detachment were compared with those in infants without retinal detachment. RESULTS: A striking difference in the daily intake of human milk was found between the infants with or without retinal detachment when their gestational ages at birth were matched. The infants without retinal detachment were fed more human milk (67-83% volume of total nutritional intake) as compared to those with retinal detachment (24-38% volume of total nutritional intake) at a specific postnatal period, 5-7 weeks postnatal age. CONCLUSIONS: Human milk may contain some beneficial factors to reduce the severity of ROP. Identifying these factors in human milk may contribute to development of a strategy to rescue premature infants from blindness.     

进一步完善早产儿视网膜病的筛查制度

早产儿视网膜病(ROP)是儿童致盲的重要原因,已成为发展中国家日益突出的医疗和社会问题。防治ROP的关键是建立科学的筛查制度。文章主要讲述筛查制度中所涉及的筛查对象、筛查时机、随访方案等,以及如何管理该制度,以期对所有符合标准的早产儿做到一个不漏地筛查和全程随访,从而做到早期诊断和及时治疗,以降低致盲率。     

IGF-1 and retinopathy of prematurity in the preterm infant

BACKGROUND: Retinopathy of prematurity (ROP) continues to be a major cause of blindness in children. Although ablation of the retina reduces the incidence of blindness by suppressing the neovascular phase of ROP, the visual outcomes after treatment are often poor. Preventive therapy is required and will likely come from a better understanding of the pathophysiology of the disease. OBJECTIVES: To study the role of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) in both the proliferative phase of ROP (phase II) and in the early phase when blood vessels are lost. METHODS: Using both a mouse model of ROP and clinical studies the relationship between IGF-1, VEGF and both vessel loss and vessels proliferation in the retina was studied. RESULTS: IGF-1 is required for maximum VEGF activation of vascular endothelial cell proliferation and survival pathways. IGF-1 levels are deficient after premature birth, setting the stage for retinal vascular loss and ROP. CONCLUSIONS: Restoration of IGF-1 to levels found in utero may help prevent ROP.     

早产儿视网膜病的手术治疗

早产儿视网膜病(retinopathy of prematurity,ROP)是儿童重要的可预防的致盲性疾病,需早期发现、及时治疗,对于阈值期及阈值前1型病变首选激光光凝治疗,如果进展为视网膜脱离需进行巩膜扣带术或玻璃体手术,文章对ROP手术治疗的现状及进展进行评述。     

AP-ROP in an infant with minimal oxygen exposure

Abstract   Retinopathy of prematurity (ROP) is a multifactorial disease affecting the developing retinal vasculature and remains an important cause of blindness in very preterm infants. Rush disease, or aggressive posterior ROP (AP-ROP), progresses rapidly to stage 5 disease without exhibiting the classical course that includes stages 1–3. We describe an infant with minimal exposure to oxygen who developed AP-ROP that led to bilateral retinal detachments and a poor visual outcome, despite following current recommended screening guidelines.     

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。     

Neovascularization in retinopathy of prematurity: opposing actions of neuronal factors GPR91 and semaphorins 3A

Retinopathy of prematurity (ROP) is a major cause of severe visual deficits in children. This review focuses on the role of newly identified factors from retinal neurons, which through their opposing actions on vascular development contribute to ROP. These hypoxia-generated mediators include the Krebs cycle intermediate, succinate acting via GPR91, and the neuronal guidance molecule Semaphorin 3A. CONCLUSION: Neuron-derived factors guide retinal vascularization and are major contributors to the pathogenesis of ROP.     

Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control

Globally at least 50,000 children are blind from retinopathy of prematurity (ROP) which is now a significant cause of blindness in many middle income countries in Latin American and Eastern Europe. Retinopathy of prematurity is also being reported from the emerging economies of India and China. The characteristics of babies developing severe disease varies, with babies in middle and low income countries having a much wider range of birth weights and gestational ages than is currently the case in industrialized countries. Rates of disease requiring treatment also tend to be higher in middle and low income countries suggesting that babies are being exposed to risk factors which are, to a large extent, being controlled in industrialised countries. The reasons for this "third epidemic" of ROP are discussed as well as strategies for control, including the need for locally relevant, evidence based criteria which ensure that all babies at risk are examined.     

Leitlinie zur augenärztlichen Screeninguntersuchung von Frühgeborenen

Retinopathy of prematurity (ROP) is caused by disrupted development of the blood vessels of the retina. The acute phase, i.e., the first months of life, can be followed by life-long scarring. Although retinal changes in the acute phase usually resolve spontaneously, significant functional impairment or blindness are possible. Coagulation therapy can reduce the frequency of such unfavorable developments. The prerequisite for its use is reliable and prompt diagnosis of ROP stages requiring therapy by means of screening all preterm neonates at risk by experienced ophthalmologists. The present guideline introduces new evidence-based results on the treatment of ROP and includes modifications of previous therapy concepts. The challenges to the ophthalmological examiner, criteria for selecting neonates to be screened, intervals between and completion of ophthalmological examinations and their procedures and implementation, as well as the indication for coagulation therapy are presented here. In addition, follow-up of former preterm neonates will be discussed.