Analysis of Ocular and Neurodevelopmental Function for Retinopathy of Prematurity

NCT05186155 | Unknown

• 1 other identifier: 201801566A3
• Study Type: observational
• Target: 510
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research project is to identify the long-term outcome of neurodevelopment in patients with retinopathy of prematurity(ROP) and the treatment of anti-vascular endothelial growth factor (VEGF) such as intravitreal injection of bevacizumab (IVB), ranibizumab, or aflibercept.Investigators propose this study hopefully to have a better understanding of the long-term safety of anti-VEGF on the treatment of ROP. Studies in both animalsand humans have found evidence of systemic bevacizumab exposure after IVB. In an animal study, IVB at an early age could result in more systemic bevacizumab exposure. Our study has further shown that VEGF levels in ROP infants were depressed for 8 weeks after IVB. VEGF plays an important role in neurogenesis in embryos and preterm newborns. In previous reports, blocking VEGF-A expression has been shown to impair brain vascularization and lead to neuron apoptosis in the retina. In addition, VEGF has been found to be lower in preterm pups compared to term pups, and this has been proposed to relate to the neurodevelopmental delay and reduced growth of the cerebral cortex in premature infants. Since neurogenesis may continue in the third trimester, further inhibition of serum VEGF in preterm newborns may have long-term effects on the development of the central nervous system and other systems. Currently, most studies reported neurodevelopmental outcomes in anti-VEGF treated premature infants before 2 years of age, and only one study reported 5 year outcomes. Our recent study also found that the neurodevelopmental outcomes at the mean age of 1.52 ± 0.59 years after birth were similar between ROP patients who did not require treatment and ROP patients with IVB treatment. Unfortunately, the value of early assessments of cognition in predicting cognitive functioning at school age and older is questionable.Many developmental deficits in cognition, emotional and behavioral development, and social adaptive functioning may emerge at older ages in the absence of neurodevelopmental impairment in toddlerhood. Visuomotor function deficit are also noted at school age in children who had normal development at 3 years of age. The above studies demonstrate a need for longer follow-up of the preterm infants to fully comprehend their neurodevelopmental outcomes. To our knowledge, currently there are no reports of neurodevelopmental outcomes in anti-VEGF treated premature infants beyond 5 years of age. Therefore, investigators propose this study hopefully to have a better understanding of the long-term safety of anti-VEGF on the treatment of ROP. This study will aim at (1) Understanding the long-term neurodevelopmental outcomes of intravitreal injection of anti-VEGF comparing to standard laser treatment for ROP in premature infants. (2) Compare the long-term neurodevelopmental outcomes in premature infants with ROP treated by different anti-VEGF agents. (3) Analysis the long-term ocular morphological and functional outcomes in premature infants with ROP with prior treatments. Investigators plan to recruit patients from our previous ROP cohort, who now aged 3 to12-years-old. Thepatients will be divided to six groups:premature without ROP (Group 0); ROP without treatment (Group 1); ROP with laser photocoagulation treatment (Group 2); ROP with anti-VEGF treatment (Group 3); ROP with laser photocoagulation + anti-VEGF treatment (Group 4); Fullterm (Group 5).Serialneurodevelopmental tests, such as Chinese Child Development Inventory (CCDI), Child Behavior Checklist (CBCL), The Berry-Buktenica Developmental Test of Visual-Motor Integration, Bayley Scales of Infant Development, Wechsler children's intelligence test- fourth editionand other neurocognitive tests and questionnaires, will be performed yearly in all patients. The detailed visual tests, such as best-corrected visual acuity, slit lamp examination, indirect ophthalmoscopy,and optical coherence tomography (OCT) will be performed every 6 months. Main outcome measures will be neurodevelopmental outcomes. The neurodevelopmental outcomes will be analyzed longitudinally and in the cross-section fashion. These outcomes will be compared between the five groups, and in the subgroup analysis. Secondary outcomes will include ocular morphological and functional results of these children. Finally, the correlation of ocular resultswith neurodevelopment outcomes will be analyzed. Investigators are fortunate to have the opportunity of following a longitudinal ROP cohort and monitor their long-term outcomes. In the long-term, this studywill improve understanding the long-term safety of anti-VEGF treatment for ROP, which is a heatedly debated topic. Investigators will also have a better knowledge which anti-VEGF might be safer than the other. Understanding these facts will help us to come up with a better treatment strategy for ROP in the future.

Conditions

Retinopathy of Prematurity; Neurodevelopmental Abnormality

Keywords

retinopathy of prematurity; neurodevelopment; bevacizumab; ranibizumab; aflibercept; Berry-Buktenica Developmental Test; Wechsler children's intelligence test

Outcome Measures

Primary Outcomes (1)

• Wechsler children's intelligence test- fourth edition

  The WISC-IV measures intellectual ability of children from 6 to 16 years. It was developed to provide an overall measure of general cognitive ability, and also measures of intellectual functioning in Verbal Comprehension (VC), Perceptual Reasoning (PR), Working Memory (WM) and Processing Speed (PS). The VC, PR, WM, and PS subscales provide scores for the Verbal Comprehension Index (VCI), the Perceptual Reasoning Index (PRI), the Working Memory Index (WMI), and the Processing Speed Index (PSI), respectively. Together, the VCI, PRI, WMI, and PSI provide the overall level of intelligence, or Full Scale IQ (FSIQ). A scaled score of 10 is the mean and scaled scores that deviate 3 units reflect a standard deviation. Similar subtests are then combined into Primary Index Scales that have a mean of 100 and standard deviation of 15. These numbers help determine the classification for performance.

  once a year, from the date of patient inclusion, up to 3 years

Secondary Outcomes (1)

• corrected visual acuity (BCVA)

  twice a year, from the date of patient inclusion, up to 3 years

Study Arms (6)

premature baby without ROP (Group 0)

ROP: retinopathy of prematurity

ROP without treatment (Group 1)

ROP: retinopathy of prematurity

ROP with laser photocoagulation treatment (Group 2)

ROP: retinopathy of prematurity

Procedure: Severe ROP

ROP with anti-VEGF treatment (Group 3)

ROP: retinopathy of prematurity anti-VEGF: anti-Vascular Endothelial Growth Factor

Procedure: Severe ROP

ROP with laser photocoagulation + anti-VEGF treatment (Group 4)

ROP: retinopathy of prematurity anti-VEGF: anti-Vascular Endothelial Growth Factor

Procedure: Severe ROP

Fullterm baby (Group 5)

Fullterm baby

Interventions

Severe ROP PROCEDURE

The treatment for ROP was either primary intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) or laser photocoagulation or vitrectomy, and the indication for treatment was type 1 ROP, as defined by the ETROP Study.

ROP with anti-VEGF treatment (Group 3); ROP with laser photocoagulation + anti-VEGF treatment (Group 4); ROP with laser photocoagulation treatment (Group 2)

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

We recruited patients from our previous ROP cohort now aged 3 to12-years-old. The patients were divided to six groups: Premature without ROP (Group 0); ROP without treatment (Group 1); ROP with laser photocoagulation treatment (Group 2); ROP with anti-VEGF treatment (Group 3); ROP with laser photocoagulation + anti-VEGF treatment (Group 4); Fullterm (Group 5)

You may qualify if:

• Patients now aged 3 to12-years-old
• Premature without ROP
• ROP without treatment
• ROP with laser photocoagulation treatment
• ROP with anti-VEGF treatment
• ROP with laser photocoagulation + anti-VEGF treatment
• Fullterm

You may not qualify if:

• Patients have brain's disease
• Patients have Scleral buckling which is a type of eye surgery
• Patients have Trans pars plana vitrectomy which is a type of eye surgery
• Patients have other eye surgery
• Patients have nystagmus
• Patients can not Cooperate to complete the text

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Department of Ophthalmology, Chang Gung Memorial Hospital.

Linkou District, Taoyuan, 33305, Taiwan

RECRUITING

MeSH Terms

Conditions

Retinopathy of Prematurity

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Wei-Chi Wu, M.D., PhD

CONTACT

886-3-3281200; weichi666@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professer&Chairman

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: January 11, 2022
• Study Start: January 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2022
• Last Updated: January 31, 2022

Record last verified: 2022-01

Locations

TW (1)