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Completed

NCT Number: NCT02887157

Analyzing Retinal Microanatomy in ROP

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.

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Key information

Age range

30 week and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Florida, Gainesville, Florida, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Swept Source OCT

Device

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

Magnetic Resonance Imaging

Other

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

Scavenged blood collection

Other

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.

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. Retinal microanatomy grading from Swept Source Optical Coherence Tomography (SSOCT)

    Time frame: 4 years

    Grading and measurement of retinal microanatomy from SSOCT images

  6. Brain MRI grading

    Time frame: 3 years

    Grading and analysis of brain MRI scans collected at approximately term-equivalent age

  7. Visual acuity scores

    Time frame: 3 years

    Analyses of data from Teller Visual acuity testing at 9 months

  8. Neurodevelopmental scores

    Time frame: 3 years

    Analysis of Bayley Scales-III Neurodevelopmental testing at age 2 years

  9. Peripheral retinal microanatomy grading

    Time frame: 4 years

    Analyses of peripheral retinal microanatomy at the vascular-avascular junction as recorded via SSOCT

  10. 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

  11. Maximum ROP stage as determined during clinical evaluation

    Time frame: 4 years

    Analysis of maximum ROP stage per eye as determined during clinical evaluation

Secondary outcomes

  1. Neuroinflammatory marker scores

    Time frame: 2 years

    Analysis of left over blood samples to determine presence and severity of neuroinflammation

  2. Presence of non-ROP ocular conditions

    Time frame: 4 years

    Analysis of clinical data for strabismus,, amblyopia, refractive error, nystagmus

  3. 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. 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

  5. Clinician's decision to treat

    Time frame: 4 years

    Analysis of the clinician's decision to treat

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

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

Registry information

Official study title

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

Acronym: BabySTEPS

Important dates

Study start
2016
Primary completion
2020
Study completion
2021
First posted
Sep 2, 2016
Registry last updated
Feb 10, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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