Bedside Optical Retinal Assessment of Hypoxic Ischemic Encephalopathy in Infants

The purpose of this study is to develop a novel noninvasive bedside optical coherence tomography (OCT) imaging technique in newborn infants with HIE that improves our ability to assess the range of retinal effects from HIE and to diagnose and monitor treatments of HIE.

Study Overview

• Status: Completed
• Conditions: Hypoxic-Ischemic Encephalopathy
• Intervention / Treatment: Device: Optical Coherence Tomography

• Study Type: Observational
• Enrollment (Actual): 57

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Health System
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Forty-eight participants with a clinical diagnosis of hypoxic ischemic encephalopathy will be recruited and consented into this study from the patient populations of Duke University and the University of Utah neonatal intensive care nurseries.

Description

Inclusion Criteria:

Infants are eligible if:

• Admitted to the intensive care nursery, outborn or inborn, with a clinical diagnosis of HIE; and with the approval of the neonatologist
• A parent or legal guardian provides written informed consent

Exclusion Criteria:

Potentially eligible infants will be excluded if:

• Congenital or chromosomal anomaly that has a profound impact on brain or eye development (e.g. anencephaly, congenital cataract or Peter's anomaly) and infants for whom there has been a clinical decision to limit life support.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Neonates with a clinical HIE diagnosis; 48 neonates with a clinical diagnosis of HIE will be recruited from the patient populations of Duke University Health System and the University of Utah. All subject will have bedside optical coherence tomography (OCT) imaging performed at various time points while in the intensive care nursery.

Device: Optical Coherence Tomography; This is an observational study in which subjects will be imaged with optical coherence tomography (OCT). OCT systems are optical imaging technology that allow non-contact imaging of the microanatomy of the retina, optic nerve head and retinal blood vessels. The OCT devices are held above (and do not touch) the eye. Unlike visible light from many examination devices, the infrared OCT beam is barely visible to the human eye as it sweeps across the retina. Thus the infant is not disturbed by the light.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal injury morphologies on optical coherence tomography	Composite injury score from presence or absence of 5 morphologies on optical coherence tomography: 1) cystoid spaces,2) ganglion cell layer abnormality, 3) paracentral acute middle maculopathy, 4) hemorrhages, 5) photoreceptor ellipsoid zone at the fovea	birth to 10 days
Retinal nerve fiber layer thickness on optical coherence tomography	Deviation in the retinal nerve fiber layer thickness in the papillomacular bundle: 0 to 150 microns	birth to 10 days
Inner macular layer thickness on optical coherence tomography	Deviation in the thickness from internal limiting membrane to outer plexiform layer across the macula (500, 1000 and 2000μm from the fovea): 0 to 500 microns	birth to 10 days
Clinical hypoxic ischemic encephalopathy score	hypoxic ischemic encephalopathy clinical score, within the first 6 hours of life, based on the modified Sarnat staging scale: mild, moderate or severe	birth to 6 hours
MRI brain injury score	MRI scoring: global score of overall injury [0-138] characterized as mild [0-11], moderate [12-32], or severe [>32].	from 4 to 14 days after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total macular layer thickness on optical coherence tomography	Deviation in total retinal thickness across macula (500, 1000 and 2000μm from the fovea): 0 to 500 microns	birth to 9 weeks
Center foveal thickness	Deviation in retinal thickness at the foveal center	birth to 9 weeks
Center ellipsoid zone thickness	Deviation in retinal thickness at the foveal center: 0 to 100 microns	birth to 9 weeks
pattern of MRI injury	Patterns of injury characterized descriptively as white matter, focal cortical, deep nuclear brain matter, or global based on the scoring methods of Bednadrek N et al.	from 4 to 14 days after birth
Choroidal thickness on optical coherence tomography	Deviation in choroidal thickness across macula(500, 1000 and 2000μm from the fovea): 20 to 800 microns	birth to 9 weeks
Optic nerve head morphology	optic nerve head elevation and cup as a composite morphology: normal, excavated, elevated, bowing of retinal pigment epithelium	birth to 9 weeks
thickness of macular nerve fiber layer	Deviation in nerve fiber layer thickness across macula(500, 1000 and 2000μm from the fovea): 0 to 100 microns	birth to 9 weeks
thickness of macular ganglion cell layer	Deviation in ganglion cell layer thickness across macula(500, 1000 and 2000μm from the fovea): 0 to 200 microns	birth to 9 weeks
thickness of inner nuclear layer	Deviation in total retinal thickness across macula (500, 1000 and 2000μm from the fovea): 0 to 400 microns	birth to 9 weeks
thickness of inner plexiform layer	Deviation in inner plexiform layer thickness across macula (500, 1000 and 2000μm from the fovea): 0 to 100 microns	birth to 9 weeks
thickness of photoreceptor layer	Deviation in total retinal thickness across macula(500, 1000 and 2000μm from the fovea): 0 to 200 microns	birth to 9 weeks
Longitudinal change in retinal injury morphologies on optical coherence tomography	Composite injury score from presence or absence of 5 morphologies on optical coherence tomography: 1) cystoid spaces,2) ganglion cell layer abnormality, 3) paracentral acute middle maculopathy, 4) hemorrhages, 5) photoreceptor ellipsoid zone at the fovea	birth to 9 weeks
Longitudinal change in retinal nerve fiber layer thickness on optical coherence tomography	Deviation in the retinal nerve fiber layer thickness in the papillomacular bundle: 0 to 150 microns	birth to 9 weeks
Longitudinal change in inner macular layer thickness on optical coherence tomography	Deviation in the thickness from internal limiting membrane to outer plexiform layer across the macula (500, 1000 and 2000μm from the fovea): 0 to 500 microns	birth to 9 weeks
Late clinical hypoxic ischemic encephalopathy score	Composite hypoxic ischemic encephalopathy severity score based on: examination after rewarming, early feeding behavior score, seizure score and electroencephalogram score	1 to 8 days

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Eye Institute (NEI)
• Investigators: Principal Investigator: Cynthia Toth, MD, Duke University

Publications and helpful links

General Publications

• Tran-Viet D, Wong BM, Mangalesh S, Maldonado R, Cotten CM, Toth CA. HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING THROUGH THE UNDILATED PUPIL IN INFANTS BORN PRETERM OR WITH HYPOXIC INJURY OR HYDROCEPHALUS. Retina. 2018 Aug;38(8):1588-1594. doi: 10.1097/IAE.0000000000001735.
• Mangalesh S, Tran-Viet D, Pizoli C, Tai V, El-Dairi MA, Chen X, Viehland C, Edwards L, Finkle J, Freedman SF, Toth CA. Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy. Graefes Arch Clin Exp Ophthalmol. 2020 Sep;258(9):2039-2049. doi: 10.1007/s00417-020-04738-0. Epub 2020 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2018
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): February 28, 2021

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Infant; Newborn; Optical Coherence Tomography
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: Pro00100417; 1R21EY029384 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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