Healthy Little Eyes

Official title

Visual Function as a Novel Outcome Measure Following Neonatal Hypoxic Ischemic Encephalopathy

Overview

The purpose of this research study is to gather more information on how eye injury is related to a baby's future development and see if eye function and brain test results can be used, along with current measures, to better diagnose and treat babies with hypoxic-ischemic encephalopathy (HIE). Participants will undergo up to two eye exam sessions, involving both Visual Evoked Potential (VEP) and Electroretinogram (ERG) exams.

Detailed description

Specific Aims/Study Objectives:

In this proposed longitudinal study, the investigators hypothesize that the early visual function findings will correlate with the neurodevelopmental and neuroimaging outcomes in children who sustain HIE. The investigators will test this hypothesis through the following specific aims:

* Specific Aim 1 will determine the correlation of the ERG results as a measure of the retinal function obtained at around birth, 3, 9, 18 or 30 months of life and neurodevelopmental-neuroimaging outcomes from birth through 36 months. * Specific Aim 2 will determine the correlation of the VEP as a measure of the visual cortical function obtained at around birth, 3, 9, 18 or 30 months of life and neurodevelopmental-neuroimaging outcomes from birth through 36 months. * Specific Aim 3 will collect ERG and VEP results from well babies in the Newborn Nursery and compare results to neonates with HIE. * Specific Aim 4 will determine if machine learning will predict the clinical outcomes using VEP, ERG, and EEG waveform data, as well as MR imaging files (exploratory)

As health care providers, the investigators' goal is to develop a noninvasive and novel quantitative tool to improve the neurodevelopmental outcome of neonates and to support them in attaining maximum functional potential in childhood and beyond.

Interventions

• Device Visual Evoked Potential (VEP)
  Small gold-cup electrodes will be placed on the participant's head using a small dot of adhesive paste. The handheld device is then connected to the electrodes, and the participant's eyes are exposed to a light flicker. Each eye will be tested separately, and while testing one eye, the other eye may be patched.
• Device Electroretinogram (ERG)
  Skin electrodes will be placed under each eye. Eyes will then be exposed to a flashing light. Each eye will be tested separately and while testing one eye, the other eye may be patched.

Primary outcome measures

• To evaluate the correlation between retinal function and neurodevelopmental outcomes [Time frame: Through 30 months of life]
• To evaluate the correlation between retinal function and neuroimaging outcomes [Time frame: Within first 5 days of life]
• To evaluate the correlation between visual cortical function and neurodevelopmental outcomes [Time frame: Through 30 months of life]
• To evaluate the correlation between visual cortical function and neuroimaging outcomes [Time frame: Within first 5 days of life]
• Compare ERG results between healthy babies and babies with HIE [Time frame: Within first 5 days of life]
• Report Shape of the VEP results for healthy babies and babies with HIE [Time frame: Within first 5 days of life]
• Compare Amplitude of the VEP results between healthy babies and babies with HIE [Time frame: Within first 5 days of life]
• Compare Latency of the VEP results between healthy babies and babies with HIE [Time frame: Within first 5 days of life]
• Compare Transocular Shape, Amplitude, and Latency Difference of the VEP results between healthy babies and babies with HIE [Time frame: Within first 5 days of life]

Eligibility criteria

HIE Neonate Inclusion Criteria:

• Inpatient Neonates diagnosed with HIE
• Pediatric patients who are less than 78 hours of age at the time of enrollment
• Participants whose parent/legal guardian is able to complete consenting process in English

HIE Neonate Exclusion Criteria:

• Participants with prenatally diagnosed or congenital brain and/or eye abnormalities not associated with HIE, including but not limited to microphthalmia, anophthalmia, congenital cataract, eye or eyelid coloboma, congenital glaucoma, CMV retinitis, optic nerve hypoplasia, aniridia, cryptophthalmos, globe abnormalities
• Participants who have a known central nervous system illness other than HIE, including but not limited to congenital brain malformations or congenital hydrocephalus
• Participants whose parent/legal guardian is unable to provide informed consent, including participants who are in foster care, participants within state custody, and participants of minor parents

Waisman, AFCH NBFU, or CERU Clinic HIE Patient Inclusion Criteria:

• Pediatric patients who have a diagnosis of HIE and present to the Newborn Follow Up Clinic
• Pediatric patients who are less than 36 months of age at the time of enrollment
• Participants whose parent/legal guardian is able to complete consenting process in English

Waisman, AFCH NBFU, or CERU Clinic HIE Patient Exclusion Criteria:

• Participants with prenatally diagnosed or congenital brain and/or eye abnormalities not associated with HIE, including but not limited to microphthalmia, anophthalmia, congenital cataract, eye or eyelid coloboma, congenital glaucoma, CMV retinitis, optic nerve hypoplasia, aniridia, cryptophthalmos, globe abnormalities
• Participants who have a known central nervous system illness not associated with HIE and its complications. Complications may include seizures, hydrocephalus, and stroke, which are NOT exclusionary. Examples of exclusionary conditions include but are not limited to traumatic brain injury outside the perinatal period, meningitis, or diagnosis of brain tumor
• Participants whose parent/legal guardian is unable to provide informed consent, including participants who are in foster care, participants within state custody, and participants of minor parents

Well Baby Inclusion Criteria:

• Patient in Meriter's Newborn Nursery
• ≥37 and <42 weeks gestational age
• 5-minute Apgar Score ≥7
• Occipital Frontal Circumference (OFC) is within average limits for age (<97th percentile and >3rd percentile)

Well Baby Exclusion Criteria:

• Admitted to the NICU for any reason
• Known genetic abnormality
• Diagnosed with HIE
• Diagnosed with Hypoglycemia
• Diagnosed with Hyperbilirubinemia requiring phototherapy
• Identified prenatal exposure to substances, including illicit drugs, alcohol, and/or tobacco
• Known or suspected neonatal infection requiring treatment (e.g., antibiotics)
• TORCH infections
• Abnormal newborn hearing screen
• Abnormal toxicology screening
• Identified as large for gestational age (LGA) or small for gestational age (SGA)
• Participants with prenatally diagnosed or congenital eye abnormalities, including but not limited to microphthalmia, anophthalmia, congenital cataract, eye or eyelid coloboma, congenital glaucoma, CMV retinitis, optic nerve hypoplasia, aniridia, cryptophthalmos, globe abnormalities, and nystagmus
• Subjects who have a known central nervous system illness or malformation, including but not limited to congenital brain malformations or congenital hydrocephalus
• Participants whose parent/legal guardian is unable to provide informed consent, including subjects who are in foster care, subjects within state custody, and subjects of minor parents
• The attending medical team does not approve

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

United States · 1 center

• University of Wisconsin — Madison

Identifiers

NCT: NCT05971446 · 2019-1243 · SMPH\PEDIATRICS\PICU · Protocol Version 6/19/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗