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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: â¯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.
RESUMO
PURPOSE: To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children. 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 7-15 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. 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.
RESUMO
BACKGROUND: Functional visual disorders in children and adolescents are an important but challenging differential diagnosis. What is characteristic is the discrepancy between the symptomatology and the objective findings. The aim of our work was to analyse the data of those patients who were cared for at our clinic with the diagnosis "functional visual disorders". PATIENTS AND METHODS: A retrospective data analysis was performed: age < 18 years, with diagnosis "functional visual disorder" 2011 to 2020. Historical and clinical data were extracted from the patient's file. In addition, parents or patients were contacted using a questionnaire about current symptoms. The study was approved by the cantonal ethics committee of Zürich (KEK Nr. 2020-01268). RESULTS: A total of 92 patients were identified, and analysis could be performed in 53% (49/92; 32 female, 17 male) with available consent. The age ranged from 3 to 18 years (median 10.5 years) with a follow-up of 1 to 58 months (median 7 months). The most common symptoms were bilateral visual loss (55%) and/or blurred vision (18%) with headache (35%), motility pain (14%), photophobia (4%), dizziness (4%), and malaise (2%). A reduction in distant (22/49 bilateral, 9/49 unilateral) and near (24/49 bilateral, 3/49 unilateral) visual acuity was documented. Subjective visual acuity reduction was no longer detectable in 20% of patients at testing. Psychological distress was documented in 13/49 patients. Moisturising eye drops (18/49), eyeglass prescription (15/49), or no therapy (20/49) was recommended. Subjective and/or objective improvement was documented at follow-up in 49% (24/49). The questionnaire was answered in 86%: no complete remission of visual symptoms (10/42), remission within 1 week (14/41), 1 month (3/41), 2â-â6 months (8/41), 1 year (6/41). There was no correlation between duration of visual symptoms and age at onset or gender. The consultation at our clinic was reported as "supportive and helpful" in 31/42 patients. CONCLUSION: Despite a low incidence during the history, the psychosocial and psychological component should not be neglected.
