Bedside Optical Retinal Assessment of Hypoxic Ischemic Encephalopathy in Infants

Study Overview
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Brief Summary
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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.

Official Title
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Bedside Optical Retinal Assessment of Hypoxic Ischemic Encephalopathy in Infants

Conditions
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Hypoxic-Ischemic Encephalopathy

Intervention / Treatment
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* Device: Optical Coherence Tomography


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 20 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neonates with a clinical HIE diagnosis<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Optical Coherence Tomography, Newborn, Infant