Retinal Microanatomy in Retinopathy of Prematurity (BabySTEPS2)

NCT04995341 | Recruiting DMC FDA Device

• 2 other identifiers: Pro00107978R01EY025009
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Retinopathy of Prematurity

Keywords

Optical Coherence Tomography (OCT); Optical Coherence Tomography Angiography (OCTA); Retinopathy of Prematurity; Neurodevelopment; Visual Acuity

Outcome Measures

Primary Outcomes (10)

• Optotype Visual acuity scores (Cohort 1 only)

  HOTV visual acuity at the 5-year study visit. Visual acuity is recorded as the last line of the HOTV chart on which over 50% of the 4 symbols are identified correctly identified by the participant. If the participant is not capable of performing HOTV, then Teller cards will be used for preferential-looking visual acuity assessment. With Teller, acuity is determined by the smallest cycles per degree.

  5-year study visit

• Visual function scores (Cohort 1 only)

  Visual function at the 4.75-year visit is measured by the presence or absence of strabismus, nystagmus, and amblyopia

  4.75-year study visit

• Neurodevelopmental scores at 2-year study visit (Cohort 1 only)

  Neurodevelopmental testing at the 2-year neurodevelopment study visit: a) Bayley Scales of Infant and Toddler Development: Scores motor skills with the standardized mean motor score of 100; less than 85 indicates mild impairment; less than 70 indicates moderate to severe impairment.

  2-year study visit

• Retinal thickness at the fovea and surrounding optic nerve as measured by OCT reading (Cohort 1-3)

  Retinal thickness (microns) at the fovea and surrounding optic nerve.

  Up to 42 weeks post-menstrual age

• Microanatomy as measured by OCT reading

  Combination of presence and severity of: retinal vessel tortuosity, vascular abnormality score by OCT (VASO), aggressive ROP, extra retinal neovascularization, vitreous abnormalities, shunt vessels, retinoschisis and retinal detachment.

  Up to 42 weeks post-menstrual age

• Microanatomy as measured by retinal photo reading (Cohort 3 only)

  Combination of presence and severity of retinal vessel tortuosity, aggressive ROP, extra retinal neovascularization, shunt vessels, vitreous opacities, vitreous haze, retinoschisis and retinal detachment.

  Up 42 weeks post-menstrual age

• Microanatomy as measured by clinical exam (Cohort 1-3)

  Clinical determination of combination presence and severity of retinal vessel tortuosity, aggressive ROP, extra retinal neovascularization, shunt vessels, vitreous opacities, vitreous haze, retinoschisis and retinal detachment.

  Up to 42 weeks post-menstrual age

• Measurement of stress of imaging (Cohort 3 only)

  Assessment of stress and discomfort using modified CRIES score (crying 0-4; facial expression 0-2; heart rate beats per minute; change in respiratory support) during each eye imaging and compared to baseline pre-imaging score adverse events recorded during imaging (bradycardia, tachycardia, desaturation, emesis, and ocular adverse events e.g. conjunctival hemorrhage)

  Up to 42 weeks post-menstrual age

• Assessment of ease of imaging (Cohort 3 only)

  Based on Likert scales (1-5)

  Up to 42 weeks post-menstrual age

• ROP vascular severity score (Cohort 3 only)

  Based on a combination of relative retinal vessel tortuosity score, extraretinal neovascularization and aggressive ROP.

  Up to 42 weeks post-menstrual age

Secondary Outcomes (6)

• Neurodevelopmental scores at 5-year study visit (Cohort 1 only)

  5-year study visit

• Neurodevelopmental scores at 5-year study visit (Cohort 1 only)

  5-year study visit

• Neurodevelopmental scores at 5-year study visit (Cohort 1 only)

  5-year study visit

• Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)

  5-year study visit

• Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)

  5-year study visit

Other Outcomes (3)

• Axial length as measured in millimeters (Cohort 1 only)

  4.75-year study visit

• OCT grading from commercial OCT device

  4.75-year study visit

• Reference standard score for ROP vascular severity (Cohort 3 only)

  Up to 42 weeks post-menstrual age

Study Arms (4)

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

EXPERIMENTAL

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

Device: Investigational ultracompact OCT and OCTA system

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

EXPERIMENTAL

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.

Device: Investigational ultracompact OCT and OCTA system

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

EXPERIMENTAL

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.

Device: Investigational ultracompact OCT and OCTA system; Device: retinal photographs

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

EXPERIMENTAL

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.

Device: Investigational ultracompact OCT and OCTA system

Interventions

Investigational ultracompact OCT and OCTA system DEVICE

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

Also known as: optical coherence tomography, optical coherence tomography angiography

Cohort 1: Functional and structural outcomes in children after bedside OCT imaging in infancy; Cohort 2: Test of bedside OCT imaging data to predict RW-ROP or ROP progression; Cohort 3: Comparison of ROP imaging with investigational OCT versus retinal camera; Cohort 4: Adult and pediatric participants enrolled for imaging during system development

retinal photographs DEVICE

retinal photographs with a commercial portable bedside widefield fundus camera system

Also known as: RetCam

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Duke University: lead
• University of Pennsylvania: collaborator
• National Eye Institute (NEI): collaborator

Study Sites (2)

Duke University Eye Center

Durham, North Carolina, 27705, United States

RECRUITING

University of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Related Publications (24)

• 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.

  PMID: 28085775 BACKGROUND

• 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.

  PMID: 29190238 BACKGROUND

• 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.

  PMID: 29621379 BACKGROUND

• 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.

  PMID: 30326081 BACKGROUND

• 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.

  PMID: 30506013 BACKGROUND

• 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.

  PMID: 30935662 BACKGROUND

• 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.

  PMID: 30790072 BACKGROUND

• 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.

  PMID: 31143506 BACKGROUND

• 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.

  PMID: 30543348 BACKGROUND

• 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.

  PMID: 31548134 BACKGROUND

• 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.

  PMID: 31246250 BACKGROUND

• 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.

  PMID: 31825990 BACKGROUND

• 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.

  PMID: 32472201 BACKGROUND

• 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.

  PMID: 32879772 BACKGROUND

• 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.

  PMID: 33045380 BACKGROUND

• 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.

  PMID: 33599735 BACKGROUND

• 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.

  PMID: 33150050 BACKGROUND

• 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.

  PMID: 32891695 BACKGROUND

• 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.

  PMID: 32942022 BACKGROUND

• 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.

  PMID: 32927150 BACKGROUND

• 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.

  PMID: 33792625 BACKGROUND

• 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.

  PMID: 27591053 BACKGROUND

• 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.

  PMID: 23719310 BACKGROUND

• 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.

  PMID: 29799932 BACKGROUND

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Tomography, Optical Coherence

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Tomography, Optical; Optical Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Investigative Techniques

Study Officials

• Cynthia A Toth, MD

  Duke University Eye Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cynthia A Toth, MD

CONTACT

919-684-5631; cynthia.toth@duke.edu

Michelle N McCall, MCAPM, BA

CONTACT

919-684-0544; michelle.mccall@duke.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: August 6, 2021
• Study Start: August 16, 2021
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be made available after the completion of the Retinal Microanatomy in ROP (BabySTEPS2) Study
• Access Criteria: Data requests must be submitted to the PI or the Coordinating Center. Approved recipients will need to enter into a data sharing agreement. Costs for compilation and access to the datasets will be the responsibility of the recipients.

Locations

US (2)