Analyzing Retinal Microanatomy in ROP (BabySTEPS)

February 8, 2023 updated by: Duke University

Analyzing Retinal Microanatomy in Retinopathy of Prematurity to Improve Care (BabySTEPS)

Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that may impact vision in vulnerable preterm neonates for a lifetime. This study utilizes new technology to determine visual and neurological development of very preterm infants in the intensive care nursery, during a period of rapid growth of the retina, optic nerve and brain. The long-term goal of this study is to help improve preterm infant health care via objective bedside imaging and analysis that characterizes early critical indicators of poor vision, neurological development and ROP, which will rapidly translate to better early intervention and improved future vision care.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that may impact vision in vulnerable preterm neonates for a lifetime. Clinical care of infants with ROP decreases the likelihood of blindness, but abnormal vision is common, especially in those with disease severe enough to require treatment. Because it has not been possible to distinguish whether disease and/or maldevelopment that affects specific retinal cells and/or the central nervous system (CNS) cause the vision loss, especially when it is less severe, there has been no strategy to prevent subnormal acuity in the majority of infants treated for ROP.

The interval that a preterm infant at risk for ROP spends in an intensive care nursery (ICN) is a time of rapid retinal development. Clinicians and researchers do not know how local, CNS and systemic development and disease processes are reflected in the retinal microanatomy. Abnormalities in the retina during infancy are likely early predictors of later vision problems and developmental delay. From study of preterm retinal substructures, brain anatomy, connectivity and functional networks and neuroinflammatory biomarkers this study will elucidate the pathway by which local retinal anatomic changes impact and may predict later subnormal vision and CNS function. The results of this research will enable the investigator to: distinguish ocular from non-ocular contributions to vision loss; guide future treatment directed to modify retinal anomalies such as edema; and determine which microanatomic retinal biomarkers are best to monitor effects of ROP, and effects of systemic therapies on the eye and brain. In contrast to indirect ophthalmoscopy or photography, novel non-contact ocular imaging at the bedside would enable direct telemedicine screening for ROP and for neural development in multiple nurseries.

The long-term goal is to help improve preterm infant health care via objective bedside imaging and analysis that characterizes early critical indicators of poor vision, neurological development and ROP. This will rapidly translate to early intervention and improved future vision care. Specific goals of this research are threefold: to implement technological innovations to improve optical coherence tomography (OCT) imaging in non-sedated infants in the ICN; to distinguish elements of retinal microanatomy which predict maldevelopment of visual pathway and poor neurodevelopment that may impact vision in preterm infants; and to delineate which elements and regions (posterior and peripheral) of preterm infant OCT-derived retinal microanatomy best inform us about severity of disease and visual outcomes in infants with ROP.

In addition to providing a breakthrough method for bedside analysis of the very preterm (VPT) infant posterior and peripheral retina, this study will provide the pediatric ophthalmologic and telemedicine community with methods to distinguish microanatomic markers that predict infants at risk for abnormal vision, visual pathway injury, poor functional development and progression of ROP (and combinations thereof). These biomarkers will be useful for determining ophthalmic and CNS therapeutic interventions and monitoring their impact on the visual pathway and will thus likely cross over with relevance to other infant eye and brain disease.

Study Type

Observational

Enrollment (Actual)

191

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32611
        • University of Florida
    • Missouri
      • Saint Louis, Missouri, United States, 63130
        • Washington University
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Eye Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

This study will have approximately 160 participants recruited and consented into the study at Duke University Health System. Of the 160 participants, 135 will be pediatric participants (of which 110 will be infants in the ICN) and 25 will be healthy adult volunteers. Infants in the ICN must meet the American Association of Pediatrics eligibility of ROP screening (Infants with a birth weight of ≤1500 g or gestational age of 30 weeks), and is age ≤ 34 6/7 weeks postmenstrual age at first visit.

Description

Inclusion Criteria:

  • Health care provider, knowledgeable of protocol, agrees that study personnel could contact the Parent/Legal Guardian
  • Parent/Legal Guardian is able and willing to consent to study participation for the infant with likelihood of follow up at standard of care visits at approximately 1-month, 4-months, 9-months and 2 years corrected age
  • Infant/child undergoing clinically indicated examination under anesthesia (for the testing of the custom widefield OCT lens) that may or may not have eye pathology. (Only for Aim 1)
  • Infant meets the American Association of Pediatrics eligibility of ROP screening (Infants with a birth weight of ≤1500 g or gestational age of 30 weeks), and is age ≤ 34 6/7 weeks postmenstrual age at first visit
  • Adults (over the age of 18 years) that may or may not have eye pathology (Only for Aim *Participants in Aim 3 will not have a brain MRI, collection of scavenged blood for neuroinflammatory markers, or the neurodevelopmental 2-year visit.

Exclusion Criteria:

  • Participant or Parent/Legal Guardian (of infant/child) unwilling or unable to provide consent
  • Adult participant or infant/child has a health or eye condition that preclude eye examination or retinal imaging (e.g. corneal opacity such as with Peters anomaly or cataract)
  • Infant has a health condition, other than prematurity, that has a profound impact on brain development (e.g. anencephaly). Note that infants with brain hemorrhages and sequelae would be eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Specific Aim 1B

Specific Aim 1B (implement technical innovations to improve OCT imaging in non-sedated infants in the ICN: (1B) extend imaging to the vascular-avascular junction via a wide-field lens).

Aim 1B only: 50 participants (25 healthy adult volunteers and 25 pediatric participants under going examination under anesthesia

  • Healthy adult volunteers will have SSOCT imaging of both eyes with the novel ultralight handpiece up to 10 times.
  • Pediatric participants undergoing examination under anesthesia will have SSOCT imaging of both eyes with the novel ultralight handpiece once during their EUA in the Duke Eye Center Operating Rooms (OR). These participants will be enrolled into the study at DUHS including the Duke Eye Center clinics and OR for testing the custom widefield lens.
Device: Swept Source OCT
The swept source optical coherence tomography device was developed at Duke University as the result of collaboration between the Departments of Ophthalmology and Biomedical Engineering. The SSOCT system has a 100kHz repetition rate, 1050nm-centered swept-source light source (Axsun Technologies). This swept-source system allows near real-time OCT imaging during movement while imaging and it provides better OCT imaging of the choroid. The SSOCT system is a non-contact device and therefore does not touch the eye.
Other Names:
  • SSOCT
  • Swept Source Optical Coherence Tomography
Specific Aim 2

Specific Aim 2 (distinguish elements of retinal microanatomy that predict maldevelopment of visual pathway and poor neurodevelopment that may impact vision in preterm infants) includes 68 very preterm infants undergoing the following during evaluation for ROP.

  1. Swept Source OCT imaging of both eyes with the novel ultralight handpiece before or after ROP examination, timed with each examination. The axial length of the eye may be measured after the ROP exam.
  2. Non-sedated research brain Magnetic Resonance Imaging will be obtained in 68 participants prior to discharge from the nursery whenever possible (as close to term age as possible). In the case of an early infant discharge to another hospital, every effort will be made to obtain brain MRI prior to transfer or an outpatient non-sedated brain MRI at near term age.
  3. Scavenged blood collection: Residual samples of serum/plasma in the laboratory will be collected for neuroinflammatory marker testing.
Device: Swept Source OCT
The swept source optical coherence tomography device was developed at Duke University as the result of collaboration between the Departments of Ophthalmology and Biomedical Engineering. The SSOCT system has a 100kHz repetition rate, 1050nm-centered swept-source light source (Axsun Technologies). This swept-source system allows near real-time OCT imaging during movement while imaging and it provides better OCT imaging of the choroid. The SSOCT system is a non-contact device and therefore does not touch the eye.
Other Names:
  • SSOCT
  • Swept Source Optical Coherence Tomography
Other: Magnetic Resonance Imaging
Non-sedated research brain MRI: Magnetic resonance imaging (MRI) is a minimal risk procedure that uses a magnet and radio waves to make diagnostic medical images of the body. There have been no ill effects reported from exposure to the magnetism or radio waves used in this test. However, it is possible that harmful effects could be recognized in the future. A known risk is that the magnet could attract certain kinds of metal. Therefore, we will carefully ask about metal within the body. If there is any question about potentially hazardous metal within the body, MRI imaging will not be performed. We will also keep the examining room locked so that no one carrying metal objects can enter while the child is in the scanner.
Other Names:
  • MRI
Other: Scavenged blood collection
Serum/plasma (residual in the laboratory) collected as part of clinically indicated care will be shipped to the University of Florida for neuroinflammatory biomarker testing to identify central nervous system cellular injury.
Specific Aim 3

Specific Aim 3 (delineate which elements and regions (posterior) or (peripheral) of preterm infant OCT-derived retinal microanatomy best inform us about severity of disease and visual outcomes in infants with ROP will include the same 68 participants plus an additional 42 very preterm infants undergoing evaluation for ROP and visual function but who will not be in the neurodevelopmental study and thus will not have brain MRI, 2-year Bayley Scales testing or neuroinflammatory marker testing on scavenged blood. The Specific Aim 3 subjects will undergo the following:

  1. Swept Source OCT imaging of both eyes with the novel ultralight handpiece as described in Aim 2. The axial length of the eye may be measured after the ROP exam.
  2. After imaging with the original lens (ultralight handpiece) both eyes will be imaged with the widefield OCT lens. before or after the ROP exam.
  3. Ocular and systemic health data will be extracted from the study participant's medical record.
Device: Swept Source OCT
The swept source optical coherence tomography device was developed at Duke University as the result of collaboration between the Departments of Ophthalmology and Biomedical Engineering. The SSOCT system has a 100kHz repetition rate, 1050nm-centered swept-source light source (Axsun Technologies). This swept-source system allows near real-time OCT imaging during movement while imaging and it provides better OCT imaging of the choroid. The SSOCT system is a non-contact device and therefore does not touch the eye.
Other Names:
  • SSOCT
  • Swept Source Optical Coherence Tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Initiate ICN research imaging with the novel ultralight hand piece and high speed SSOCT (Aim 1A)
Time Frame: 4 years
Start-up of research imaging in the intensive care nursery using the new ultralight hand piece and swept source OCT
4 years
Number of infants with reproducible imaging of the peripheral vascular-avascular junction (Aim 1B)
Time Frame: 4 years
Analysis of reproducibility of imaging of the peripheral vascular-avascular junction in infants
4 years
Number of microns of retinal thickness and distance from foveal to ellipsoid zone band as seen on retinal vascular imaging using infant specific automated image processing
Time Frame: 3 months
Develop infant-specific automated image processing/analyses for retinal vascular imaging
3 months
Number of microns of retinal thickness and distance from foveal to ellipsoid zone band as seen from multi-layer segmentation using infant specific automated image processing (1C)
Time Frame: 3 months
Develop infant-specific automated image processing/analyses or multi-layer segmentation
3 months
Retinal microanatomy grading from Swept Source Optical Coherence Tomography (SSOCT)
Time Frame: 4 years
Grading and measurement of retinal microanatomy from SSOCT images
4 years
Brain MRI grading
Time Frame: 3 years
Grading and analysis of brain MRI scans collected at approximately term-equivalent age
3 years
Visual acuity scores
Time Frame: 3 years
Analyses of data from Teller Visual acuity testing at 9 months
3 years
Neurodevelopmental scores
Time Frame: 3 years
Analysis of Bayley Scales-III Neurodevelopmental testing at age 2 years
3 years
Peripheral retinal microanatomy grading
Time Frame: 4 years
Analyses of peripheral retinal microanatomy at the vascular-avascular junction as recorded via SSOCT
4 years
ROP severity grade of retinal microanatomy by OCT
Time Frame: 4 years
Severity of ROP as determined by analysis of posterior and peripheral retinal microanatomy
4 years
Maximum ROP stage as determined during clinical evaluation
Time Frame: 4 years
Analysis of maximum ROP stage per eye as determined during clinical evaluation
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuroinflammatory marker scores
Time Frame: 2 years
Analysis of left over blood samples to determine presence and severity of neuroinflammation
2 years
Presence of non-ROP ocular conditions
Time Frame: 4 years
Analysis of clinical data for strabismus,, amblyopia, refractive error, nystagmus
4 years
ROP specifics from clinical examination
Time Frame: 4 years
ROP specifics including zone, plus or preplus disease, stage per clock hour, vitreous hemorrhage from clinical examination
4 years
ROP specifics from OCT imaging
Time Frame: 4 years
ROP specifics including zone, plus or preplus disease, stage per clock hour, vitreous hemorrhage from OCT imaging
4 years
Clinician's decision to treat
Time Frame: 4 years
Analysis of the clinician's decision to treat
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

University of Pennsylvania
Washington University School of Medicine
National Eye Institute (NEI)
University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 22, 2016

Primary Completion (ACTUAL)

December 31, 2020

Study Completion (ACTUAL)

April 15, 2021

Study Registration Dates

First Submitted

August 25, 2016

First Submitted That Met QC Criteria

August 29, 2016

First Posted (ESTIMATE)

September 2, 2016

Study Record Updates

Last Update Posted (ACTUAL)

February 10, 2023

Last Update Submitted That Met QC Criteria

February 8, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00069721
  • R01EY025009-01A1 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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