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The Effect of High-Dose Erythropoietin Perinatally on Retinal Function in School-Aged Children Born Extremely or Very
Lorena Sisera1, James V M Hanson1, Jonas Füglistaler2
1From the Department of Ophthalmology (L.S., J.V.M.H., B.M.J., S.P., C.G.K.), University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Insights
High-dose recombinant human erythropoietin (rhEPO) given to very preterm infants did not affect long-term retinal function. Premature birth may have minor effects on vision, potentially lessened by rhEPO treatment.
Area of Science:
- Neonatal Medicine
- Ophthalmology
- Neuroscience
Background:
- Premature birth can impact long-term visual development.
- Recombinant human erythropoietin (rhEPO) is used to treat anemia in preterm infants.
- The long-term effects of high-dose rhEPO on vision are not fully understood.
Purpose of the Study:
- To assess the long-term effects of high-dose rhEPO on retinal and visual function in children born extremely or very preterm.
- To compare outcomes in children who received rhEPO versus placebo during the perinatal period.
Main Methods:
- Follow-up of a randomized clinical trial cohort.
- Electroretinogram (ERG) testing to measure retinal function.
- Ophthalmological and orthoptic examinations to exclude comorbidities.
Main Results:
- No significant differences in ERG parameters were found between the rhEPO and placebo groups.
- Minor, potentially clinically insignificant differences in ERG peak times were observed between preterm and healthy control groups.
- Secondary outcomes, including visual acuity and color discrimination, were comparable across groups.
Conclusions:
- High-dose rhEPO administered perinatally does not have measurable long-term effects on retinal function in extremely or very preterm children.
- Premature birth may induce subtle, likely insignificant, changes in childhood retinal function.
- rhEPO may offer a partial mitigation of these effects.
Purpose:
To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm.
Design:
Randomized, double-blind clinical trial follow-up plus cohort study.
Methods:
Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
Study Population:
Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period.
Inclusion Criteria:
participation in an ongoing neuropediatric study (EpoKids), written informed consent.
Exclusion Criteria:
previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited.
Inclusion Criteria:
term birth, informed consent.
Exclusion Criteria:
any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses.
Observation Procedures:
The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group.
Main Outcome Measures:
Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only).
Results:
No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups.
Conclusions:
Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.
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