Retinopathy of prematurity: Recommendations for screening

Retinopathy of prematurity (ROP) is a disorder of the developing retinal blood vessels of the preterm infant. New recommendations for screening and treatment of ROP have been published in the past few years. Current evidence suggests that screening infants with gestational ages of 30 6/7 weeks or less (regardless of birth weight) and birth weights of 1250 g or less is a strategy with a very small likelihood that an unscreened baby would have treatable ROP. Individual centres may choose to extend birth weight screening criteria to 1500 g. Initial screening should be performed at 31 weeks' postmenstrual age in infants with gestational ages of 26 6/7 weeks or less at birth, and at four weeks' chronological age in infants with gestational ages of 27 weeks or more at birth by an ophthalmologist skilled in the detection of ROP. Follow-up examinations are conducted according to the ophthalmologist's recommendation. Infants with high-risk prethreshold ROP and threshold ROP are referred for retinal ablative therapy. Developing processes for ROP screening, documenting results and communicating results to parents as well as health professionals involved in the infant's care are important responsibilities for all nurseries providing care for preterm infants.     

Retinopathy of prematurity screening by non-retinologists

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

Retinopathy of prematurity: New developments bring concern and hope

Blindness from retinopathy of prematurity (ROP) in Australian and New Zealand is an uncommon event although 3% of <31 weeks gestation infants receive treatment for the disease. New world‐wide estimates of the incidence of blindness from ROP are much higher than previously at 20 000 children annually. The impact of severe ROP can be reduced through good evidence‐based care of very preterm infants and careful organisation of eye examinations and follow‐up services. Recent oxygen saturation targeting trial results might mean the adoption of higher targets than formerly in very preterm infants and will require vigilance to ensure all eligible infants are examined appropriately. A true screening examination for acute ROP might involve non‐opthalmologists obtaining photographic retinal images and remote reading of these. Although treatment with laser gives good outcomes, there is interest in intravitreal anti‐vascular endothelial factor agents, but issues concerning the systemic safety and retinal results of such treatment are unresolved.     

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.     

On safety, pharmacokinetics and dosage of bevacizumab in ROP treatment - a review

Off-label intravitreal use of the vascular endothelial growth factor (VEGF) antibody bevacizumab for retinopathy of prematurity (ROP) increases despite lack of studies on safety, pharmacokinetics and dosage in developing individuals. Systemic absorption has been considered negligible. A literature search was performed with emphasis on potential adverse systemic effects in developing individuals. CONCLUSION: Intravitreal bevacizumab enters the general circulation, suppresses plasma VEGF levels and remains in the blood for more than 8 weeks in primates. Possible adverse effects on VEGF-dependent development must be considered.     

Serum levels of IGF1 are a useful predictor of retinopathy of prematurity

Objective: To ascertain whether insulin‐like growth factor 1 (IGF1) is associated with retinopathy of prematurity (ROP) and is a useful predictor of the disease. Although its aetiopathogenesis is multifactorial, development of the disease appears to be related to a deficiency in IGF1, a hormone that acts together with vascular endothelial growth factor in the normal angiogenesis in the retina. Design: Prospective study for a 30‐month period. Participants: A total of 74 premature newborn babies, of less than 1500 g and/or 32 weeks’ gestational age or less. Testing: To determine the development and severity of ROP. Main outcome measures: Serum levels of IGF1 were measured once a week from birth until 40 weeks corrected gestational age in each subject. Results: Of our subjects, 32.4% developed some form of ROP, and all those ROP patients had the following characteristics at birth (median ± standard deviation scores): low weight (1098 ± 188 vs. 1393 ± 285 g), short length (36.74 ± 1.77 vs. 38.89 ± 3.08 cm), small cranial perimeter (26.03 ± 1.74 vs. 27.93 ± 1.81 cm) and young gestational age (29.7 ± 1.78 vs. 31.3 ± 1.79 weeks) (p < 0.05). Other factors previously associated with ROP that were also observed with statistically significant frequency in our ROP patients were bronchopulmonary dysplasia, intracranial haemorrhage, the need for erythrocyte transfusion or treatment with erythropoietin and sepsis (all p < 0.05). Levels of IGF1 at the 3rd week post‐partum, independent of gestational age at birth, were clearly lower in the group who developed ROP (29.13 vs. 43.16 ng/mL, p < 0.05). A value of 30 ng/mL of IGF1 in the third week post‐partum was found to have a 90% sensitivity in the diagnosis of ROP. A rapid rise in IGF1 levels between the 3rd and 5th weeks appeared to be related to the development of a higher stage of ROP. Conclusion: Determination of IGF1 serum levels in the 3rd week post‐partum, independent of gestational age at birth, provides a sufficient and reliable prognostic tool and allows the identification of a group of patients at high risk of developing the disease.     

Retinopathy of prematurity: An update on screening and management

Retinopathy of prematurity is a proliferative disorder of the developing retinal blood vessels in preterm infants. The present practice point reviews new information regarding screening and management for retinopathy of prematurity, including the role of risk factors in screening, optimal scheduling for screening examinations, pain management, digital retinal photography and antivascular endothelial growth factor therapy.     

Retinopathy of prematurity: A systematic review of the literature

OBJECTIVE:

To assist in the diagnosis of retinopathy of prematurity (ROP) to facilitate treatment in a timely manner to help prevent blindness.

DATA SOURCES:

Systematic review using MEDLINE including the following key words, “retinopathy of prematurity”, “retrolental fibroplasia”, “blind”, “blindness”, “vision screening”, “cryotherapy”, “cryosurgery”, “laser” and “ablative therapy”. The bibliographies of the references found using the above techniques were scanned for references missed in the primary search.

DATA SELECTION:

Eight population-based studies examining the incidence and severity of ROP were identified. Other studies of ROP were included because they contributed to an understanding of the natural history, treatment or long term outcome of ROP.

DATA EXTRACTION:

Data was analyzed cumulatively from the population-based studies to determine the incidence of ROP. For the natural history, treatment and schedule of eye examinations, data was reported from individual studies.

DATA SYNTHESIS:

Infants at greatest risk of ROP were 1500 g or less at birth, or 30 weeks gestational age or younger. An inverse relationship existed between the incidence and severity of ROP and birth weight or gestational age. The age of onset of ROP was four to six weeks; however, a few newborns presented with an aggressive form of ROP called ’rush disease’ as early as three weeks of age. For those requiring treatment for ROP, the maximum severity was about 11 weeks of age. Long term follow-up for refractive errors was more effective between six and 12 months and again at four years.

CONCLUSION:

Very premature or very low birth weight infants are at highest risk of ROP. Based upon published information, an optimal screening schedule is recommended and a long term follow-up strategy is provided.     

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.     

血管内皮生长因子及胰岛素样生长因子-1在早产儿视网膜病变中的作用

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

玻璃体腔内注射抗血管内皮生长因子治疗早产儿视网膜病复发的危险因素分析

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

早产儿视网膜病变筛查及相关因素分析

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

Retinopathy of prematurity and bilirubinno clinical evidence for a beneficial role of bilirubin as a physiological anti-oxidant

The prevention of retinopathy of prematurity (ROP) remains a persistent problem. A previous report has focused on the possible protective effect of bilirubin on the development of ROP. These results still await clinical confirmation by other research groups. Therefore, we undertook a retrospective clinical study trying to confirm this attractive hypothesis. Twelve premature newborns under 32 weeks of gestation with ROP stage 3–4 were matched for gestational age with 12 infants without ROP. Data were collected about the infant's characteristics, medical illnesses, ventilatory settings and treatments. The total serum bilirubin concentrations between the 1 st and 8th postnatal day were also gathered. The two matched groups were comparable as to their basic data, clinical characteristics and treatment, except for a slight, but significant longer duration of phototherapy for group ROP o (mean, 50.2 h; SD 48,6 vs 31.6 h; SD 42.7 in ROP 3-4;P=0.02). No statistical difference relative to bilirubin was found between the two groups, neither when expressed as daily mean concentrations, nor as area under the curve (AUC) (mean, ROP 0: 17876.7; SD 6077.3 vs 18888.4; SD 55552.7 in ROP 3-4;P=0.404) or AUC/h (mean, ROP 0: 135.1; SD 36.3 vs 144.1; SD 23.2 in ROP 3-4;P=0.515). Our findings do not confirm the hypothesis of a clinically measurable, beneficial role of bilirubin on the development 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.     

Perinatal infection, inflammation, and retinopathy of prematurity

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

早产儿视网膜病1082例筛查报告及诊治分析

目的 探讨早产儿视网膜病(ROP)的早期诊治方法,分析其筛查结果.方法 由眼底病专科医生应用双目间接眼底镜对本院新生儿科2004年7月至2009年6月收治的胎龄＜34周或出生体质量＜2000 g的住院早产儿进行ROP筛查.首次筛查时间为纠正胎龄32～34周或生后4～6周,对检出的阈值期或阈值前期1型ROP(重症)患儿全部给予眼底激光光凝术,对视网膜血管未发育成熟、1～2期或阈值前期2型(轻度)ROP患儿进行密切随访,直至视网膜血管发育至锯齿缘或发展成为重症.对所有的临床资料进行回顾性分析.结果 5年共收治早产儿2 295例,符合筛查标准的早产儿1 082例,占47.14%;检出ROP总阳性病例154例,占筛查对象的14.23%(154/1082);其轻度ROP86例,占7.94%(86/1 082);重症ROP 68例,占6.28%(68/1 082).68例重症ROP患儿中,有6例出院后随访期间发现进展为重症ROP而再入院,有2例放弃治疗1年后证实全部失明.66例(132只眼)接受各种治疗,其中63例单用光凝术治疗;3例急进性后极ROP中2例采用玻璃体腔内注入血管内皮生长因子拮抗剂(Avastin)联合光凝术治疗,1例单用光凝术治疗者治疗后仍出现部分视网膜脱离,经玻璃体视网膜手术后仍失明;随访结果65例成功的保存了视力,成功率98.48%(65/66).在观察期间未达到光凝治疗条件,因原发病恶化死亡10例,经光凝治疗后的患儿未出现死亡.结论 ROP筛查是防止ROP病情发展的有效措施,对重症ROP及时给予光凝术治疗是安全有效的方法,对急进性后极ROP可用玻璃体腔内注入血管内皮生长因子拮抗剂联合光凝术治疗抢救视力.