目的:研究围产期大剂量重组人促红细胞生成素(rhEPO)对早产儿黄斑结构和血管发育的长期影响。
方法:随机化,双盲临床试验随访加队列研究。
方法:设置:眼科,苏黎世大学医院,苏黎世,瑞士。
方法:来自正在进行的神经儿科研究(EpoKids)的7-15岁的极度或极早产儿童。这些先前已被随机分配以围生期接受高剂量rhEPO或安慰剂。
方法:参与EpoKids研究,书面知情同意书(IC)。
方法:既往眼外伤或手术;与早产无关的视网膜或发育性疾病。年龄相当的足月出生儿童被纳入健康对照(HC)组。
方法:足月分娩,IC.
方法:任何眼部或视觉异常,高屈光不正。在完成所有分析之前,检查人员对干预状态进行盲化。(参与者/监护人保持失明)。
方法:获得谱域OCT扫描(海德堡光谱系统)和OCTA成像(ZeissPlexElite9000)。眼科和正交检查排除了眼部合并症。
方法:OCT(中央视网膜厚度,CRT;黄斑总体积,TMV),浅丛OCTA(中央凹无血管区,FAZ;血管密度,VD;血管长度密度,VLD)参数和中央凹发育不全分级根据公布的标准。
结果:与安慰剂(n=35)相比,EPO组(n=52)的黄斑血管密度参数(VD和VLD)显着降低(p=0.015,CI-95:0.01至0.06和p=0.015,CI-95:0.74至3.64)。在EPO组和安慰剂组之间没有观察到其他显著差异。当比较干预亚组和HC时,我们发现OCT和OCTA参数有六个显著差异(FAZ,VD,VLD和CRT比较HC和EPO组;FAZ和CRT比较HC和安慰剂组)。
结论:与安慰剂相比,极早产或极早产婴儿早期高剂量rhEPO影响黄斑血管密度参数。早产(无论干预状态如何)会影响视网膜结构和血管发育。我们在黄斑血管发育方面的发现并未禁止在早产儿中使用早期高剂量EPO。为进一步了解EPO在黄斑发育中的作用及其临床意义,需要未来的研究。
OBJECTIVE: To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children.
METHODS: Randomized, double-blind clinical trial follow-up plus cohort study.
METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
METHODS: extremely or very preterm born children aged 7-15 years from an ongoing neuropediatric study (EpoKids). These had been previously randomized to receive either high-dose rhEPO or placebo perinatally.
METHODS: participation in the EpoKids Study, written informed consent (IC).
METHODS: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Term-born children of comparable age were enrolled as a healthy control (HC) group.
METHODS: term birth, IC.
METHODS: any ocular or visual abnormality, high refractive error. Examiners were blinded regarding intervention status until completion of all analyses. (Participants/guardians remain blinded).
METHODS: Spectral-domain OCT scans (Heidelberg Spectralis system) and OCTA imaging (Zeiss PlexElite 9000) were obtained. Ophthalmological and orthoptic examinations excluded ocular comorbidities.
METHODS: OCT (central retinal thickness, CRT; total macular volume, TMV), superficial plexus OCTA (foveal avascular zone, FAZ; vessel density, VD; vessel length density, VLD) parameters and foveal hypoplasia grade according to published criteria.
RESULTS: Macular vessel density parameters (VD and VLD) were significantly lower (p =0.015, CI-95: 0.01 to 0.06 and p=0.015, CI-95: 0.74 to 3.64) in the EPO group (n= 52) when compared to placebo (n=35). No other significant differences were observed between the EPO and placebo group. When comparing the intervention subgroups to HC we found six significant differences in OCT and OCTA parameters (FAZ, VD, VLD and CRT comparing HC and EPO group; FAZ and CRT when comparing HC and placebo group).
CONCLUSIONS: Early high-dose rhEPO in infants born extremely or very preterm affects macular vessel density parameters compared to placebo. Premature birth (regardless of intervention status) affects retinal structure and vascular development. Our findings on macular vascular development do not contraindicate the administration of early high-dose EPO in preterm infants. For further understanding of the role of EPO on macular development and its clinical significance, future studies are needed.