AzTrials
AzTrials

Retinopathy of PrematurityBabySTEPSNCT02887157

Analyzing Retinal Microanatomy in ROP

An observational study of Retinopathy of Prematurity and Neurodevelopmental Disorders, run by Duke University at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 30 weeks and olderHealthy volunteers can take part
What is being tested?
Swept Source OCT, Magnetic Resonance Imaging and Scavenged blood collection
Type of treatment
Medical device
How many people
191 participants
Where
4 sitesUnited States
Study dates
22 Jul 2016to 15 Apr 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 weeks and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Duke University Eye Center

    Durham, North Carolina, 27705

  • University of Florida

    Gainesville, Florida, 32611

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Washington University

    St Louis, Missouri, 63130

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Swept Source OCT, Magnetic Resonance Imaging, Scavenged blood collection
Medical subject headings
Retinopathy of Prematurity, Neurodevelopmental Disorders, Macular Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Swept Source OCTDevice

    Also called SSOCT, Swept Source Optical Coherence Tomography

    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.

  • Magnetic Resonance ImagingOther

    Also called MRI

    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.

  • Scavenged blood collectionOther

    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.

Study groups in NCT02887157
Study groupRoleWhat they receive
Specific Aim 1BSpecific 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.
Receives: Device: Swept Source OCT
Specific Aim 2Specific 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.
Receives: Device: Swept Source OCT; Other: Magnetic Resonance Imaging; Other: Scavenged blood collection
Specific Aim 3Specific 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.
Receives: Device: Swept Source OCT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Initiate ICN research imaging with the novel ultralight hand piece and high speed SSOCT (Aim 1A)

    Start-up of research imaging in the intensive care nursery using the new ultralight hand piece and swept source OCT

    Measured: 4 years

  2. Number of infants with reproducible imaging of the peripheral vascular-avascular junction (Aim 1B)

    Analysis of reproducibility of imaging of the peripheral vascular-avascular junction in infants

    Measured: 4 years

  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

    Develop infant-specific automated image processing/analyses for retinal vascular imaging

    Measured: 3 months

  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)

    Develop infant-specific automated image processing/analyses or multi-layer segmentation

    Measured: 3 months

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

    Grading and measurement of retinal microanatomy from SSOCT images

    Measured: 4 years

  6. Brain MRI grading

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

    Measured: 3 years

  7. Visual acuity scores

    Analyses of data from Teller Visual acuity testing at 9 months

    Measured: 3 years

  8. Neurodevelopmental scores

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

    Measured: 3 years

  9. Peripheral retinal microanatomy grading

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

    Measured: 4 years

  10. ROP severity grade of retinal microanatomy by OCT

    Severity of ROP as determined by analysis of posterior and peripheral retinal microanatomy

    Measured: 4 years

  11. Maximum ROP stage as determined during clinical evaluation

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

    Measured: 4 years

Secondary outcomes (5)

  1. Neuroinflammatory marker scores

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

    Measured: 2 years

  2. Presence of non-ROP ocular conditions

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

    Measured: 4 years

  3. ROP specifics from clinical examination

    ROP specifics including zone, plus or preplus disease, stage per clock hour, vitreous hemorrhage from clinical examination

    Measured: 4 years

  4. ROP specifics from OCT imaging

    ROP specifics including zone, plus or preplus disease, stage per clock hour, vitreous hemorrhage from OCT imaging

    Measured: 4 years

  5. Clinician's decision to treat

    Analysis of the clinician's decision to treat

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2016 (estimated)
  2. Study start22 Jul 2016
  3. Primary completion31 Dec 2020
  4. Study completion15 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
191 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02887157
Sponsor's protocol ID
Pro00069721
Other IDs
R01EY025009-01A1
Acronym
BabySTEPS
Status last verified
Jan 2023
First submitted
25 Aug 2016
Last updated
10 Feb 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Chen X, Mangalesh S, Tran-Viet D, Freedman SF, Vajzovic L, Toth CA. Fluorescein Angiographic Characteristics of Macular Edema During Infancy. JAMA Ophthalmol. 2018 May 1;136(5):538-542. doi: 10.1001/jamaophthalmol.2018.0467.

    PubMed 29621379

  • Lee J, El-Dairi MA, Tran-Viet D, Mangalesh S, Dandridge A, Jiramongkolchai K, Viehland C, Toth CA. LONGITUDINAL CHANGES IN THE OPTIC NERVE HEAD AND RETINA OVER TIME IN VERY YOUNG CHILDREN WITH FAMILIAL EXUDATIVE VITREORETINOPATHY. Retina. 2019 Jan;39(1):98-110. doi: 10.1097/IAE.0000000000001930.

    PubMed 29190238

  • 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.

    PubMed 28570486

  • Rothman AL, Mangalesh S, Chen X, Toth CA. Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development. Eye Brain. 2016 May 27;8:123-133. doi: 10.2147/EB.S97660. eCollection 2016.

    PubMed 28539807

  • Mangalesh S, Chen X, Tran-Viet D, Viehland C, Freedman SF, Toth CA. ASSESSMENT OF THE RETINAL STRUCTURE IN CHILDREN WITH INCONTINENTIA PIGMENTI. Retina. 2017 Aug;37(8):1568-1574. doi: 10.1097/IAE.0000000000001395.

    PubMed 28085775

  • Ong SS, Mruthyunjaya P, Stinnett S, Vajzovic L, Toth CA. Macular Features on Spectral-Domain Optical Coherence Tomography Imaging Associated With Visual Acuity in Coats' Disease. Invest Ophthalmol Vis Sci. 2018 Jun 1;59(7):3161-3174. doi: 10.1167/iovs.18-24109.

    PubMed 30025132

  • Finn AP, Chen X, Viehland C, Izatt JA, Toth CA, Vajzovic L. COMBINED INTERNAL LIMITING MEMBRANE FLAP AND AUTOLOGOUS PLASMA CONCENTRATE TO CLOSE A LARGE TRAUMATIC MACULAR HOLE IN A PEDIATRIC PATIENT. Retin Cases Brief Rep. 2021 Mar 1;15(2):107-109. doi: 10.1097/ICB.0000000000000762.

    PubMed 29979253

  • Hsu ST, Chen X, House RJ, Kelly MP, Toth CA, Vajzovic L. Visualizing Macular Microvasculature Anomalies in 2 Infants With Treated Retinopathy of Prematurity. JAMA Ophthalmol. 2018 Dec 1;136(12):1422-1424. doi: 10.1001/jamaophthalmol.2018.3926. No abstract available.

    PubMed 30326081

  • Ong SS, Cummings TJ, Vajzovic L, Mruthyunjaya P, Toth CA. Comparison of Optical Coherence Tomography With Fundus Photographs, Fluorescein Angiography, and Histopathologic Analysis in Assessing Coats Disease. JAMA Ophthalmol. 2019 Feb 1;137(2):176-183. doi: 10.1001/jamaophthalmol.2018.5654.

    PubMed 30476946

  • Hsu ST, Chen X, Ngo HT, House RJ, Kelly MP, Enyedi LB, Materin MA, El-Dairi MA, Freedman SF, Toth CA, Vajzovic L. Imaging Infant Retinal Vasculature with OCT Angiography. Ophthalmol Retina. 2019 Jan;3(1):95-96. doi: 10.1016/j.oret.2018.06.017. Epub 2018 Jul 26. No abstract available.

    PubMed 30935662

  • Mangalesh S, Bleicher ID, Chen X, Viehland C, LaRocca F, Izatt JA, Freedman SF, Hartnett ME, Toth CA. Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2019 Apr;257(4):677-688. doi: 10.1007/s00417-019-04274-6. Epub 2019 Feb 21.

    PubMed 30790072

  • Smith LEH, Hellstrom A, Stahl A, Fielder A, Chambers W, Moseley J, Toth C, Wallace D, Darlow BA, Aranda JV, Hallberg B, Davis JM; Retinopathy of Prematurity Workgroup of the International Neonatal Consortium. Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials. JAMA Ophthalmol. 2019 Mar 1;137(3):305-311. doi: 10.1001/jamaophthalmol.2018.5984.

    PubMed 30543348

  • Hsu ST, Ngo HT, Stinnett SS, Cheung NL, House RJ, Kelly MP, Chen X, Enyedi LB, Prakalapakorn SG, Materin MA, El-Dairi MA, Jaffe GJ, Freedman SF, Toth CA, Vajzovic L. Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography. Ophthalmology. 2019 Dec;126(12):1703-1711. doi: 10.1016/j.ophtha.2019.06.028. Epub 2019 Jul 15.

    PubMed 31548134

  • 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.

    PubMed 32472201

  • Cai CX, Go M, Kelly MP, Holgado S, Toth CA. OCULAR MANIFESTATIONS OF PORETTI-BOLTSHAUSER SYNDROME: FINDINGS FROM MULTIMODAL IMAGING AND ELECTROPHYSIOLOGY. Retin Cases Brief Rep. 2022 May 1;16(3):270-274. doi: 10.1097/ICB.0000000000000991. Epub 2020 Mar 17.

    PubMed 32195884

Questions about this trial

What is this clinical trial studying?

An observational study of Retinopathy of Prematurity and Neurodevelopmental Disorders, run by Duke University at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Initiate ICN research imaging with the novel ultralight hand piece and high speed SSOCT (Aim 1A) (time frame: 4 years). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02887157, which also lists 36 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in