Cerebral/ Cortical Visual Impairment: Screening, Identification and Outcome Prediction in Neonates (CVI)

The Vision Study: Cerebral/ Cortical Visual Impairment (CVI)

Cerebral/Cortical Visual Impairment (CVI) is the leading cause of childhood visual impairment in the United States and other industrialized countries. CVI is a brain-based visual disorder in which visual acuity or visual fields are reduced despite a normal eye examination or greater-than-expected visual impairment relative to ocular pathology. CVI is increasingly recognized in children with neurological conditions, yet it often remains undiagnosed until later childhood, delaying opportunities for early intervention.

Population-based studies suggest that CVI is more common than previously understood. Recent estimates indicate that over 180,000 individuals in the United States aged 0-22 years may have diagnosed or likely CVI, with only a minority formally identified. Children with CVI frequently have co-occurring neurological conditions, including cerebral palsy, epilepsy, developmental delays, or genetic disorders. Infants born preterm or with conditions such as hypoxic-ischemic encephalopathy (HIE), perinatal stroke, or white matter injury are at particularly high risk. Prospective research also shows that a substantial proportion of infants born very preterm exhibit behavioral features of CVI later in childhood.

Despite improvements in neonatal neurocritical care, early detection of CVI remains challenging. Current clinical practice focuses on managing conditions such as HIE, perinatal stroke, periventricular leukomalacia, and other brain injuries, but there is limited research evaluating structured early identification pathways for CVI in infancy. Diagnostic tools such as brain MRI and Visual Evoked Potentials (VEP) have shown potential for identifying brain-based visual dysfunction, but their integration into early predictive models for CVI has not been fully explored.

This study addresses a critical gap in pediatric care by prospectively evaluating high-risk neonates using clinical, neuroimaging, neurophysiologic, and standardized developmental assessments through 24 months of age. Early identification of CVI may support timely referral for visual rehabilitation and developmental services, potentially improving long-term functional outcomes. Developing a predictive model for early CVI detection will contribute to improved clinical pathways, enhance early diagnosis, and reduce the long-term educational and social burden associated with undetected CVI. Ultimately, this research aims to improve outcomes and quality of life for infants at risk for brain-based visual impairment.

Study Overview

• Status: Recruiting
• Conditions: Preterm Less Than 32wks With IVH, WMI/PVL; Late Preterm or Term (37-42wks) With Neonatal Encephalopathy Treated With Hypothermia for HIE
• Intervention / Treatment: Other: Prospective Clinical and Neurodevelopmental Data Collection

Detailed Description

The study is a prospective observational study designed to follow preterm and term infants who are at high risk for Cerebral/ Cortical Visual Impairment (CVI). Preterm Infants born before 32 weeks gestational age with conditions such germinal matrix/intraventricular hemorrhage (IVH), white matter injury (WMI including periventricular leukomalacia (PVL), and late term and term infants with Hypoxic-Ischemic Encephalopathy (HIE) or prenatal Stroke will be enrolled during the neonatal intensive care unit (NICU) stay and monitored through a structured follow-up schedule. The study focuses on data collection using advanced diagnostic imaging and neurodevelopmental assessments without introducing randomization or experimental interventions.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Mohamed El-Dib, MD; Phone Number: +15712016409; Email: mel-dib@bwh.harvard.edu
• Study Contact Backup: Name: Mohamed El-Dib

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital, and Boston Children's Hospital
      • Contact: Mohamed El-Dib, MD,
      • Principal Investigator: Gena Heidry, MD
      • Principal Investigator: Ellen Grant, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes preterm and term infants at high risk for cerebral visual impairment due to neurological injury diagnosed in the neonatal period. This includes:

• Preterm infants born <32 weeks gestation with intraventricular hemorrhage or white matter injury
• Late preterm (34-36 weeks) and term (37-42 weeks) infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia or diagnosed with perinatal stroke

Eligible infants are enrolled during their initial hospitalization and followed longitudinally into early childhood to assess visual development, neurodevelopmental outcomes, and early signs of cerebral visual impairment. Parent(s) or legal guardian(s) must be willing and able to provide informed consent.

Description

Inclusion Criteria:

• Preterm infants born < 32 weeks gestational age with any of the following:
• Germinal matrix/intraventricular hemorrhage (IVH)
• White matter injury (WMI), including periventricular leukomalacia (PVL)
• Late preterm infants (born 34-36 weeks gestation) or term infants (born 37-42 weeks gestation) with:
• Neonatal encephalopathy treated with therapeutic hypothermia for suspected hypoxic-ischemic encephalopathy (HIE)
• Infants diagnosed with perinatal stroke

Parent(s) or legal guardian(s) willing and able to provide informed consent

Exclusion Criteria:

Neonates whose parent(s) or guardian(s) cannot commit to long-term follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Preterm/Term High-Risk Infants; Infants at high risk for Cerebral/Cortical Visual Impairment (CVI), including preterm infants with IVH or white matter injury, term or late preterm infants with hypoxic-ischemic encephalopathy (HIE), and infants with perinatal stroke. Participants are followed prospectively and undergo standardized clinical, neuroimaging, neurophysiologic, and developmental assessments through 24 months of age.

Other: Prospective Clinical and Neurodevelopmental Data Collection; Participants undergo standardized collection of clinical, neuroimaging, neurophysiologic, visual assessment and neurodevelopmental data as part of this prospective observational study. Data include information obtained from clinical care and scheduled follow-up assessments through 24 months of age. No interventions are assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Cerebral Visual Impairment (CVI) at 24 Months	Diagnosis of Cerebral/Cortical Visual Impairment (CVI) based on standardized clinical visual assessment performed. Outcome measure: Low, or high risk.	24 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Function assessment	Visual function evaluated using the age-appropriate CVI and parent questionnaire administered at scheduled follow-up intervals (6, 12, and 24 months per protocol), with primary reporting at 24 months.; Teller acuity Cards (testing distance: 38 cms, 55 cms 84 cms); Patti Pics or grating acuity (testing distance: 25 cms, 50 cms and 100 cms); Visual behavior scale (grade: 1, 2, or 3); Resolution Distance Visual acuity Outcome measure: Low, or high risk.	24 months
Visual Evoked Potential (VEP) Response	Assessment of cortical visual pathway response using VEP performed at 6 and 24 months per protocol, with primary reporting at 24 months. Outcome measure: low or high risk group.	24 months
Neurodevelopmental Composite Score	Standardized neurodevelopmental testing obtained as part of 12-, 18-, and 24-month clinical follow-up (e.g., Bayley-IV). Primary reporting at 24 months Outcome measure: Low-Risk: scores within or above age-expected norms; High-Risk: scores ≥1 SD below the mean (Standard Score <85) indicating developmental delay	24 months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Boston Children's Hospital
• Investigators: Principal Investigator: Mohamed El-Dib, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Chang MY, Borchert MS. Advances in the evaluation and management of cortical/cerebral visual impairment in children. Surv Ophthalmol. 2020 Nov-Dec;65(6):708-724. doi: 10.1016/j.survophthal.2020.03.001. Epub 2020 Mar 19.
• Pilling RF, Allen L, Bowman R, Ravenscroft J, Saunders KJ, Williams C. Clinical assessment, investigation, diagnosis and initial management of cerebral visual impairment: a consensus practice guide. Eye (Lond). 2023 Jul;37(10):1958-1965. doi: 10.1038/s41433-022-02261-6. Epub 2022 Oct 18.
• Sakki HEA, Dale NJ, Sargent J, Perez-Roche T, Bowman R. Is there consensus in defining childhood cerebral visual impairment? A systematic review of terminology and definitions. Br J Ophthalmol. 2018 Apr;102(4):424-432. doi: 10.1136/bjophthalmol-2017-310694. Epub 2017 Nov 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: August 19, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Hypoxic-Ischemic Encephalopathy; Neonatal Encephalopathy; Brain Injuries; Hypoxia-Ischemia, Brain; Intraventricular Hemorrhage; Periventricular Leukomalacia; Visual Evoked Potentials; White Matter Injury; Cerebral/ Cortical Visual Impairment; Vision Disorders, Cerebral/Cortical; Visual Disorders; Infant, Extremely Premature (for &lt;32 weeks GA); Germinal Matrix Hemorrhage; Prenatal Stroke
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Infant, Premature, Diseases; Infant, Newborn, Diseases; Eye Diseases; Brain Ischemia; Signs and Symptoms, Respiratory; Sensation Disorders; Craniocerebral Trauma; Trauma, Nervous System; Hypoxia, Brain; Hypoxia; Encephalomalacia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries; Hypoxia-Ischemia, Brain; Vision Disorders; Leukomalacia, Periventricular
• Other Study ID Numbers: 2025P001413

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No