Severe Retinopathy of Prematurity Is Not Independently Associated With Worse Neurodevelopmental Outcomes in Preterm Neonates

Altendahl, Marie; Sim, Myung Shin; Kokhanov, Artemiy; Gundlach, Bradley S.; Tsui, Irena; Chu, Alison

doi:10.3389/fped.2021.679546

Cited by 9 publications

(16 citation statements)

References 29 publications

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“…Fifty-eight percentage of our cohort developed amblyopia. The incidence of amblyopia in patients with has previously been reported to be as high as 27.8% in type 1 ROP (22). Finally, 58% of our cohort also developed strabismus.…”

Section: Discussionsupporting

confidence: 56%

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Aggressive Posterior Retinopathy of Prematurity: Long-Term Outcomes Following Intravitreal Bevacizumab

et al. 2022

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PurposeThe purpose of this study is to review the neonatal and early childhood course of children who were treated with intravitreal bevacizumab for APROP and identify any long term limitations these children face years after treatment.MethodsThis retrospective consecutive case series reviewed both ophthalmologic and pediatric medical records to determine ocular and neurologic function following treatment with a single injection of intravitreal bevacizumab (IVB) for APROP. Patient records were reviewed to identify the gestational age, average birth weight, gender, post-menstrual age (PMA) at the time of injection, regression status, rescue therapy events, final visual acuity, final refraction, ophthalmologic diagnoses and complications, neurologic diagnoses, and duration of follow up.ResultsThe study included 43 eyes from 13 male and 9 female children. The average gestational age was 24 weeks and average birth weight was 625.2 grams. The average follow-up was 4.08 years (range: 1.85–7.36 years). The average PMA at time of bevacizumab injection was 35.59 weeks. Thirty-five eyes eventually received laser photocoagulation at an average PMA of 53.17 weeks. All eyes in this study demonstrated regression without progression to retinal detachment. At last follow up, 67% (29/43) of eyes were able to discern letters or shapes, with an average visual acuity of 20/37. 16 (72%) children were diagnosed with perinatal neurological disorders. 59% (n = 13) developed chronic neurological impairment, 77% (n = 10) of whom developed neurodevelopmental delay. Several infants were diagnosed with endocrine disease or genetic syndromes.ConclusionsExtreme prematurity is associated with significant morbidity. Nearly all infants (92%) who developed chronic neurologic disease were diagnosed with neurologic disease during the perinatal period. Intravitreal bevacizumab, often with adjuvant photocoagulation, led to regression without detachment in 100% of eyes, with most verbal children retaining functional vision.

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Section: Discussionsupporting

confidence: 56%

“…ROP zone itself has been shown to be a risk factor for neurodevelopmental delay (33). On the other hand, the severity of ROP has not been shown to be associated with neurodevelopmental delay (22).…”

Section: Discussionmentioning

confidence: 99%

Aggressive Posterior Retinopathy of Prematurity: Long-Term Outcomes Following Intravitreal Bevacizumab

et al. 2022

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“…The primary outcome of CCS on BSID-III/IV was reported in five studies ( n = 922) at 18–24 months ( 26 , 28 , 34 , 35 , 44 ). The standard mean difference (SMD) was not different between the “no ROP” and “any ROP” groups (SMD: −0.820 to −2.43; p = 0.32; I 2 =98%).…”

Section: Resultsmentioning

confidence: 99%

Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: A systematic review and meta-analysis

et al. 2023

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BackgroundRetinopathy of prematurity (ROP) and abnormal brain development share similar risk factors and mechanisms. There has been contrasting evidence on the association of ROP with adverse neurodevelopmental outcomes.ObjectiveWe analysed the association between ROP at levels of severity and treatment with all neurodevelopmental outcomes until adolescence.Data sourceWe followed PRISMA guidelines and searched Medline and Embase between 1 August 1990 and 31 March 2022.Study selection and participantsRandomised or quasi-randomised clinical trials and observational studies on preterm infants (<37 weeks) with ROP [type 1 or severe ROP, type 2 or milder ROP, laser or anti-vascular endothelial growth factor (VEGF) treated] were included.Data extraction and synthesisWe included studies on ROP and any neurocognitive or neuropsychiatric outcomes.OutcomesThe primary outcomes were as follows: cognitive composite scores evaluated between the ages of 18 and 48 months by the Bayley Scales of Infant and Toddler Development (BSID) or equivalent; neurodevelopmental impairment (NDI; moderate to severe NDI or severe NDI), cerebral palsy, cognitive impairment; and neuropsychiatric or behavioural problems. The secondary outcomes were as follows: motor and language composite scores evaluated between the ages of 18 and 48 months by BSID or equivalent; motor/language impairment; and moderate/severe NDI as defined by the authors.ResultsIn preterm infants, “any ROP” was associated with an increased risk of cognitive impairment or intellectual disability [n = 83,506; odds ratio (OR): 2.56; 95% CI: 1.40–4.69; p = 0.002], cerebral palsy (n = 3,706; OR: 2.26; 95% CI: 1.72–2.96; p < 0.001), behavioural problems (n = 81,439; OR: 2.45; 95% CI: 1.03–5.83; p = 0.04), or NDI as defined by authors (n = 1,930; OR: 3.83; 95% CI: 1.61–9.12; p = 0.002). Type 1 or severe ROP increased the risk of cerebral palsy (OR: 2.19; 95% CI: 1.23–3.88; p = 0.07), cognitive impairment or intellectual disability (n = 5,167; OR: 3.56; 95% CI: 2.6–4.86; p < 0.001), and behavioural problems (n = 5,500; OR: 2.76; 95% CI: 2.11–3.60; p < 0.001) more than type 2 ROP at 18–24 months. Infants treated with anti-VEGF had higher odds of moderate cognitive impairment than the laser surgery group if adjusted data (gestational age, sex severe intraventricular haemorrhage, bronchopulmonary dysplasia, sepsis, surgical necrotising enterocolitis, and maternal education) were analysed [adjusted OR (aOR): 1.93; 95% CI: 1.23–3.03; p = 0.04], but not for cerebral palsy (aOR: 1.29; 95% CI: 0.65–2.56; p = 0.45). All outcomes were adjudged with a “very low” certainty of evidence.Conclusion and relevanceInfants with “any ROP” had higher risks of cognitive impairment or intellectual disability, cerebral palsy, and behavioural problems. Anti-VEGF treatment increased the risk of moderate cognitive impairment. These results support the association of ROP and anti-VEGF treatment with adverse neurodevelopmental outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42022326009.

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“…Particularly, developmental outcomes, including cognitive, language and motor functions, were similar between preterm infants with or without ROP and independent from ROP severity [ 96 ]. In line with these studies, Altendahl et al examined cognition, language, and motor scores of premature neonates at 0–36 months corrected age, screened for ROP, and found that ROP severity was not associated with worse neurodevelopmental scores [ 97 ]. Similar results were obtained in a recent study evaluating the presence of hearing loss in a large cohort of preterm infants at 18 months corrected age, revealing no significant associations between ROP and hearing impairments [ 98 ].…”

Section: The Impact Of Rop In the Central Nervous Systemmentioning

confidence: 99%

Neurosensory Alterations in Retinopathy of Prematurity: A Window to Neurological Impairments Associated to Preterm Birth

et al. 2022

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Retinopathy of prematurity (ROP) is one of the main blinding diseases affecting preterm newborns and is classically considered a vascular disorder. The premature exposure to the extrauterine environment, which is hyperoxic in respect to the intrauterine environment, triggers a cascade of events leading to retinal ischemia which, in turn, makes the retina hypoxic thus setting off angiogenic processes. However, many children with a history of ROP show persistent vision impairment, and there is evidence of an association between ROP and neurosensory disabilities. This is not surprising given the strict relationship between neuronal function and an adequate blood supply. In the present work, we revised literature data evidencing to what extent ROP can be considered a neurodegenerative disease, also taking advantage from data obtained in preclinical models of ROP. The involvement of different retinal cell populations in triggering the neuronal damage in ROP was described along with the neurological outcomes associated to ROP. The situation of ROP in Italy was assessed as well.

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Severe Retinopathy of Prematurity Is Not Independently Associated With Worse Neurodevelopmental Outcomes in Preterm Neonates

Cited by 9 publications

References 29 publications

Aggressive Posterior Retinopathy of Prematurity: Long-Term Outcomes Following Intravitreal Bevacizumab

Aggressive Posterior Retinopathy of Prematurity: Long-Term Outcomes Following Intravitreal Bevacizumab

Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: A systematic review and meta-analysis

Neurosensory Alterations in Retinopathy of Prematurity: A Window to Neurological Impairments Associated to Preterm Birth

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