Retinal Microanatomy in Retinopathy of Prematurity (BabySTEPS2)

NCT ID: NCT04995341

Last Updated: 2025-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

236 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-16

Study Completion Date

2026-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that can impact vision in vulnerable preterm neonates for a lifetime. This study tests high-speed optical coherence tomography (OCT) technology compared to conventional color photographs at the bedside of very preterm infants in the intensive care nursery, to characterize previously unseen abnormalities that can predict a need for referral for ROP treatment, or poor visual or neurological development later in life, up to pre-school age. Our long-term goal is to help improve preterm infant health and vision via objective bedside imaging and analysis that characterizes early critical indicators of ROP, and poor visual function and neurological development, which will rapidly translate to better early intervention and improved future care.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

As an increasing percentage of preterm infants survive worldwide, the number of infants at risk for retinopathy of prematurity (ROP) is increasing. These infants are also at high risk for future abnormal visual function and neurodevelopment. While current screening approaches address identifying eyes for treatment of severe ROP, there are no attempts to address the later subnormal vision of many preterm infants. In part, this is due to a lack of information about the retina beyond that of retinal vascular development. In addition, the most common method to screen for ROP remains indirect ophthalmoscopic examination by physicians with annotated drawings for documentation, a method proven to be poorly reproducible and stressful to the fragile infant. Bedside retinal photographs enable documentation and the possibility for telemedicine approaches, but lack information about retinal microanatomy, are poor quality in darkly pigmented eyes and also are stressful to the infant because of the required light exposure. We need an infant-friendly, more practical approach to evaluate ROP efficiently and additional information about ocular and neurovascular development that could lead to improved clinical care.

This research builds on our group's ability to reliably capture and process non-contact, infrared optical coherence tomography (OCT) and OCT-angiography of retinal microanatomy and microvasculature at high speed, across a wide field of view, and at the bedside in preterm infants. Our overall objectives are threefold: first, to evaluate infant microanatomy and microvascular flow findings relevant to vision and neurodevelopmental outcomes in children; second, to translate and test our imaging achievements for real-world use by nurses at the bedside and for better clinical insight and feedback; and third, to gather additional data in eyes that progress to treatment and dive deeper into the insight that they provide into pathways of disease in ROP. The investigational OCT imaging will be used in this research to gather information that is otherwise not accessible to the physician. This research will lay the groundwork for future use of infant OCT markers to guide care.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Retinopathy of Prematurity

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
While all participants have the investigational imaging, throughout image grading, the principal investigator and image analysts are masked to all health data (including retinopathy of prematurity examination findings) except age at time of imaging. The visual acuity and neurodevelopmental outcome assessors are masked to all OCT image and fundus photograph grading data.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort 1: Functional and structural outcomes in children after bedside OCT imaging in infancy

109 pediatric participants who were previously enrolled in BabySTEPS1 from July 22, 2016 - December 30, 2020 will be enrolled for follow-up neurodevelopmental testing, visual acuity, visual function testing and investigational retinal imaging

Group Type EXPERIMENTAL

Investigational ultracompact OCT and OCTA system

Intervention Type DEVICE

Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece

Cohort 2: Test of bedside OCT imaging data to predict RW-ROP or ROP progression

294 infants at risk for retinopathy of prematurity: 176 will be enrolled and have investigational bedside OCT retinal imaging, and their data will be combined with that from 118 infants who had similar imaging in BabySTEPS1 for analysis of the total group versus the indirect ophthalmoscopic clinical exam data.

Group Type EXPERIMENTAL

Investigational ultracompact OCT and OCTA system

Intervention Type DEVICE

Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece

Cohort 3: Comparison of ROP imaging with investigational OCT versus retinal camera

102 infants, who are a sub-group of the 132 enrolled in Cohort 2, will also have imaging with a conventional, commercially available, retinal camera system to compare utility, stress, and prediction and documentation of referral-warranted ROP between the camera images and those from investigational OCT.

Group Type EXPERIMENTAL

Investigational ultracompact OCT and OCTA system

Intervention Type DEVICE

Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece

retinal photographs

Intervention Type DEVICE

retinal photographs with a commercial portable bedside widefield fundus camera system

Cohort 4: Adult and pediatric participants enrolled for imaging during system development

12 awake healthy adult controls and 6 pediatric participants undergoing examination under anesthesia in the operating room will be imaged with the investigational bedside OCT for the purpose of technological development.

Group Type EXPERIMENTAL

Investigational ultracompact OCT and OCTA system

Intervention Type DEVICE

Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Investigational ultracompact OCT and OCTA system

Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece

Intervention Type DEVICE

retinal photographs

retinal photographs with a commercial portable bedside widefield fundus camera system

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

optical coherence tomography optical coherence tomography angiography RetCam

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Children previously enrolled in BabySTEPS1 (Pro00069721) that have already consented to being contacted for this school age follow on study, Cohort 1 only
* Parent/Legal Guardian is able and willing to consent to study participation with follow up approximately between 4.5 and 5 years of age (consent available in Spanish\* and English) (SA 1 only)
* Parent/Legal Guardian is able and willing to consent to study participation for the infant (SA 2 and 2c only)
* Infant/child undergoing clinically-indicated examination under anesthesia that may or may not have eye pathology (SA 2 only)
* Infant inborn or outborn at (SA 2 only):
* Duke Hospital (Years 1, 2 and 3) with birth weight ≤1000 grams, and/or 20 0/7 to 28/ 6/7 (\<29 weeks) gestational age
* Duke Hospital (Years 1, 2 and 3) at high risk to require treatment for ROP irrespective of birth weight and gestational age (e.g. pre-plus, severe ROP in zone 1, APROP, etc.)
* Duke Regional Hospital (Years 4 and 5) that meets the American Association of Pediatrics eligibility of ROP screening (Infants with a birth weight of ≤1500 g or gestational age of 30 weeks)
* Adults (over the age of 18 years) that may or may not have eye pathology (SA 2 only)

Exclusion Criteria

* Participant or Parent/Legal Guardian 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 Peter's anomaly or cataract) (SA2 only)
* Infant has a health condition, other than prematurity, that has a profound impact on brain development (e.g. anencephaly) (SA2 only)
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Pennsylvania

OTHER

Sponsor Role collaborator

National Eye Institute (NEI)

NIH

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Cynthia A Toth, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University Eye Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Duke University Eye Center

Durham, North Carolina, United States

Site Status RECRUITING

University of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics

Philadelphia, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Cynthia A Toth, MD

Role: CONTACT

919-684-5631

Michelle N McCall, MCAPM, BA

Role: CONTACT

919-684-0544

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Cynthia A Toth, MD

Role: primary

919-684-5631

Michelle N McCall, MCAPM, BA

Role: backup

9196840544

Gui-Shuang Ying, PhD

Role: primary

215-615-1514

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 28085775 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29190238 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29621379 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30326081 (View on PubMed)

Chen X, Mangalesh S, Dandridge A, Tran-Viet D, Wallace DK, Freedman SF, Toth CA. Spectral-Domain OCT Findings of Retinal Vascular-Avascular Junction in Infants with Retinopathy of Prematurity. Ophthalmol Retina. 2018 Sep;2(9):963-971. doi: 10.1016/j.oret.2018.02.001. Epub 2018 Mar 21.

Reference Type BACKGROUND
PMID: 30506013 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30935662 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30790072 (View on PubMed)

Viehland C, Chen X, Tran-Viet D, Jackson-Atogi M, Ortiz P, Waterman G, Vajzovic L, Toth CA, Izatt JA. Ergonomic handheld OCT angiography probe optimized for pediatric and supine imaging. Biomed Opt Express. 2019 Apr 29;10(5):2623-2638. doi: 10.1364/BOE.10.002623. eCollection 2019 May 1.

Reference Type BACKGROUND
PMID: 31143506 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30543348 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31548134 (View on PubMed)

Chen X, Viehland C, Tran-Viet D, Prakalapakorn SG, Freedman SF, Izatt JA, Toth CA. Capturing Macular Vascular Development in an Infant With Retinopathy of Prematurity. JAMA Ophthalmol. 2019 Sep 1;137(9):1083-1086. doi: 10.1001/jamaophthalmol.2019.2165. No abstract available.

Reference Type BACKGROUND
PMID: 31246250 (View on PubMed)

Wang KL, Chen X, Stinnett S, Tai V, Winter KP, Tran-Viet D, Toth CA. Understanding the variability of handheld spectral-domain optical coherence tomography measurements in supine infants. PLoS One. 2019 Dec 11;14(12):e0225960. doi: 10.1371/journal.pone.0225960. eCollection 2019.

Reference Type BACKGROUND
PMID: 31825990 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32472201 (View on PubMed)

Seely KR, Wang KL, Tai V, Prakalapakorn SG, Chiu SJ, Viehland C, Grace S, Izatt JA, Freedman SF, Toth CA. Auto-Processed Retinal Vessel Shadow View Images From Bedside Optical Coherence Tomography to Evaluate Plus Disease in Retinopathy of Prematurity. Transl Vis Sci Technol. 2020 Aug 7;9(9):16. doi: 10.1167/tvst.9.9.16. eCollection 2020 Aug.

Reference Type BACKGROUND
PMID: 32879772 (View on PubMed)

Chen X, Imperio R, Seely KR, Viehland C, Izatt JA, Prakalapakorn SG, Freedman SF, Toth CA. Slow progressive perifoveal vascular formation in an infant with aggressive posterior retinopathy of prematurity. J AAPOS. 2020 Oct;24(5):323-326. doi: 10.1016/j.jaapos.2020.07.007. Epub 2020 Oct 9.

Reference Type BACKGROUND
PMID: 33045380 (View on PubMed)

O'Sullivan ML, Ying GS, Mangalesh S, Tai V, Divecha HR, Winter KP, Toth CA, Chen X; BabySTEPS Group. Foveal Differentiation and Inner Retinal Displacement Are Arrested in Extremely Premature Infants. Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):25. doi: 10.1167/iovs.62.2.25.

Reference Type BACKGROUND
PMID: 33599735 (View on PubMed)

Chen X, Tai V, McGeehan B, Ying GS, Viehland C, Imperio R, Winter KP, Raynor W, Tran-Viet D, Mangalesh S, Maguire MG, Toth CA; BabySTEPS Group. Repeatability and Reproducibility of Axial and Lateral Measurements on Handheld Optical Coherence Tomography Systems Compared with Tabletop System. Transl Vis Sci Technol. 2020 Oct 21;9(11):25. doi: 10.1167/tvst.9.11.25. eCollection 2020 Oct.

Reference Type BACKGROUND
PMID: 33150050 (View on PubMed)

Shen LL, Mangalesh S, McGeehan B, Tai V, Sarin N, El-Dairi MA, Freedman SF, Maguire MG, Toth CA; BabySTEPS Group. Birth Weight Is a Significant Predictor of Retinal Nerve Fiber Layer Thickness at 36 Weeks Postmenstrual Age in Preterm Infants. Am J Ophthalmol. 2021 Feb;222:41-53. doi: 10.1016/j.ajo.2020.08.043. Epub 2020 Sep 4.

Reference Type BACKGROUND
PMID: 32891695 (View on PubMed)

Mangalesh S, Wong BM, Chen X, Tran-Viet D, Stinnett SS, Sarin N, Winter KP, Vajzovic L, Freedman SF, Toth CA. Morphological characteristics of early- versus late-onset macular edema in preterm infants. J AAPOS. 2020 Oct;24(5):303-306. doi: 10.1016/j.jaapos.2020.06.006. Epub 2020 Sep 15.

Reference Type BACKGROUND
PMID: 32942022 (View on PubMed)

Mangalesh S, McGeehan B, Tai V, Chen X, Tran-Viet D, Vajzovic L, Viehland C, Izatt JA, Cotten CM, Freedman SF, Maguire MG, Toth CA; Study of Eye Imaging in Preterm Infants Group. Macular OCT Characteristics at 36 Weeks' Postmenstrual Age in Infants Examined for Retinopathy of Prematurity. Ophthalmol Retina. 2021 Jun;5(6):580-592. doi: 10.1016/j.oret.2020.09.004. Epub 2020 Sep 11.

Reference Type BACKGROUND
PMID: 32927150 (View on PubMed)

Mangalesh S, Sarin N, McGeehan B, Prakalapakorn SG, Tran-Viet D, Cotten CM, Freedman SF, Maguire MG, Toth CA; BabySTEPS Group. Preterm Infant Stress During Handheld Optical Coherence Tomography vs Binocular Indirect Ophthalmoscopy Examination for Retinopathy of Prematurity. JAMA Ophthalmol. 2021 May 1;139(5):567-574. doi: 10.1001/jamaophthalmol.2021.0377.

Reference Type BACKGROUND
PMID: 33792625 (View on PubMed)

Campbell JP, Kalpathy-Cramer J, Erdogmus D, Tian P, Kedarisetti D, Moleta C, Reynolds JD, Hutcheson K, Shapiro MJ, Repka MX, Ferrone P, Drenser K, Horowitz J, Sonmez K, Swan R, Ostmo S, Jonas KE, Chan RV, Chiang MF; Imaging and Informatics in Retinopathy of Prematurity Research Consortium. Plus Disease in Retinopathy of Prematurity: A Continuous Spectrum of Vascular Abnormality as a Basis of Diagnostic Variability. Ophthalmology. 2016 Nov;123(11):2338-2344. doi: 10.1016/j.ophtha.2016.07.026. Epub 2016 Aug 31.

Reference Type BACKGROUND
PMID: 27591053 (View on PubMed)

Maldonado RS, Toth CA. Optical coherence tomography in retinopathy of prematurity: looking beyond the vessels. Clin Perinatol. 2013 Jun;40(2):271-96. doi: 10.1016/j.clp.2013.02.007.

Reference Type BACKGROUND
PMID: 23719310 (View on PubMed)

Zepeda EM, Shariff A, Gillette TB, Grant L, Ding L, Tarczy-Hornoch K, Cabrera MT. Vitreous Bands Identified by Handheld Spectral-Domain Optical Coherence Tomography Among Premature Infants. JAMA Ophthalmol. 2018 Jul 1;136(7):753-758. doi: 10.1001/jamaophthalmol.2018.1509.

Reference Type BACKGROUND
PMID: 29799932 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01EY025009

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00107978

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

MINImising Total Radiation EXposure in Preterm Infants
NCT06975189 NOT_YET_RECRUITING PHASE2
Premavision Cohort Follow-up
NCT03207477 TERMINATED NA