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.     

Pathogenesis of retinopathy of prematurity and possible preventive strategies

Retinopathy of Prematurity (ROP) occurs when premature birth interrupts normal retinal vascular development. Postnatal tissue oxygen levels are significantly higher than those present in utero. Oxygen therapy further increases oxygen levels in the developing retina. Hypoxia driven, VEGF mediated, retinal endothelial cell proliferation is reduced. Low IGF-1 levels may also contribute to delayed retinal vascular development. The neural structures of the peripheral avascular retina continue to develop, and become more metabolically active. Complex, as yet poorly understood abnormalities of structural and molecular interactions between immature endothelial cells and immature astrocytes at the anterior "leading edge" of retinal vascular development leads to the development of an ROP ridge. VEGF produced by the hypoxic peripheral retina, along with structural abnormalities of cell relationships within, and at the vitreoretinal interface of the ROP ridge, results in extraretinal angiogenesis - stage 3 ROP. Stage 3 ROP may resolve spontaneously, or may progress to traction retinal detachment and blindness.     

Sequelae of retinopathy of prematurity

Retinopathy of prematurity (ROP) affects preterm infants. Here we describe its revised classification and the amended treatment indications which recommend treatment at an earlier ROP stage known as ‘prethreshold’. The three global ROP epidemics are briefly discussed. ROP sequelae are discussed under four headings: visual functions, strabismus, refractive state and the effect of ROP on the structures of the eye. While ROP is potentially blinding, in general, ophthalmic outcome is similar for preterm children who did not develop ROP or in whom this was only mild (stages 1 & 2). In the main their deficits are not functionally disabling, although treatment, to correct a refractive error, strabismus or amblyopia, may be required. The outcome for children who had severe, potentially sight-threatening ROP (stages 3–5 and prethreshold) is far more variable and in a proportion of children is disabling and even blinding. Whether children who had ROP need follow-up is discussed. Finally the future role of anti-VEGF treatment is considered.     

早产儿视网膜病的研究进展

早产儿视网膜病 (retinopathyofprematurity ,ROP)是导致婴幼儿视力损伤和失明的主要原因 ,其发生率及严重程度在逐步上升。因此 ,防治ROP已成为提高早产儿生活质量的重要问题。1　早产儿视网膜病的发病机制　　ROP是视网膜血管异常改变的疾病 ,其病理生理的过程主要分为两个阶段 ,①血管关闭和消失 :当早产儿吸入高浓度氧时 ,血氧浓度升高导致视网膜高氧 ,从而正常发育的视网膜血管停止 ,已形成的视网膜血管关闭或消失。②视网膜血管异常增生 :当停止氧疗后 ,由于视网膜相对缺氧及全身营养代谢的需要导致了视网膜血管的增生 ,而新生血…     

Screening for retinopathy of prematurity

The CRYO-ROP study confirmed the success of treatment for ROP and made screening mandatory. National based screening has been influenced by the varied incidence of disease in developed and developing countries. Most ophthalmologists in developed countries screen infants born between 1000 and 1500 g and between 28 and 31 weeks gestation post menstrual age. The 1984 classification has been updated to highlight the importance of plus disease. The ETROP study findings have resulted in earlier treatment and elevated the importance of screening. Measures such as nesting may help to reduce infant distress during examination. It is important for neonatal units to have an agreed policy on screening and both neonatologist and neonatal nurses have an invaluable role. Diagnostic retinal imaging and telemedicine may have an increasing role in future screening. Timely and accurate screening is the most important first step as earlier treatment results in improved visual prognosis.     

Erythropoietin and retinopathy of prematurity

Erythropoietin (EPO) is a glycoprotein that regulates many functions of an organism: It stimulates the production of red blood cells and it has angiogenic and neuroprotective properties in newborn infants. Retinopathy of prematurity (ROP) is a frequent cause of visual impairment in preterm newborn infants and it has two distinct phases in which hypoxia-induced angiogenic factors are involved. The relationship between EPO and ROP is derived from the observation of studies done on the haematopoietic effect of EPO. The first observations suggested that a precocious treatment with EPO increases the risk of ROP, while the most recent reports suggested that the late treatment with high doses of rhEPO can increase the risk of ROP. All these studies were not designed to demonstrate the relationship between EPO and ROP. Further studies specifically designed should be performed. New ongoing studies on the neuroprotective role of EPO should consider this objective. In the mean time the use of EPO in the neonatal period should be cautious, mainly in very low birth weight infants.     

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.     

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。     

Changing profile of retinopathy of prematurity

The aim of this study was to determine the evolving trends of retinopathy of prematurity (ROP) at a tertiary neonatal intensive care unit. In an ongoing screening programme for ROP, we estimated the incidence of ROP among at-risk neonates in a tertiary care unit. We compared our data over the last 12 months (1999-2000; period II) to the previously published data (1993-94; period I) to study changes in the spectrum of the disease. The overall incidence of ROP in period II was not significantly different from the incidence in period I (32 vs. 20 per cent, p > 0.05). However, a decreasing trend in the proportion of severe ROP (stage III) from 46 to 21 per cent in the later period was noted. The need for cryotherapy also dropped significantly compared with the earlier period (8 vs. 46 per cent respectively, p < 0.05). On multivariate analysis, apnea (p < 0.001; RR = 12.5; 95 per cent CI, 3.03-50.9; clinical sepsis (p < 0.001; RR = 5.7; 95 per cent CI, 1.6-20.7); and male sex (p < 0.001; RR = 6.3; 95 per cent CI 1.6-25.5) emerged as significant risk factors. Although the incidence of ROP is static, the more severe form of the disease (stage III) is showing a decline. Our data suggests that efficient management of apnea and sepsis may be crucial in further minimizing the risk of ROP.