The Effect of Perinatal High‐Dose Erythropoietin on Retinal Structural and Vascular Characteristics in Children Born Preterm

•Macular vessel density parameters are lower in children who have received EPO compared to placebo.•OCT and OCTA parameters differ between preterm- and term-born children born of comparable age.•The clinical significance of macular structural and vascular differences is yet to be determined. To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children. Randomized, double-blind clinical trial follow-up plus cohort study. Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. Study Population: 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. Inclusion criteria: participation in the EpoKids Study, written informed consent (IC). Exclusion criteria: 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. Inclusion criteria: term birth, IC. Exclusion criteria: any ocular or visual abnormality, high refractive error. Examiners were blinded regarding intervention status until completion of all analyses. (Participants/guardians remain blinded). Observation procedures: Spectral-domain OCT scans (Heidelberg Spectralis system) and OCTA imaging (Zeiss PlexElite 9000) were obtained. Ophthalmological and orthoptic examinations excluded ocular comorbidities. Main Outcome Measures: 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. 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). 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) affec