Retinal Microanatomy in Retinopathy of Prematurity (BabySTEPS2) (BabySTEPS2)

May 19, 2026 updated by: Duke University

Analyzing Retinal Microanatomy in Retinopathy of Prematurity to Improve Care 2 and School Age Follow on Study (BabySTEPS2)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

236

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Eye Center
        • Sub-Investigator:
          • Joseph A Izatt, PhD
        • Sub-Investigator:
          • Christian Viehland, PhD
        • Contact:
        • Sub-Investigator:
          • Sharon F Freedman, MD
        • Sub-Investigator:
          • Charles M Cotten, MD, MHS
        • Sub-Investigator:
          • Kathryn E Gustafson, MD
        • Sub-Investigator:
          • Lejla Vajzovic, MD
        • Sub-Investigator:
          • Susapin G Prakalapakorn, MD
        • Sub-Investigator:
          • Xi Chen, MD, PhD
        • Sub-Investigator:
          • Sara Grace, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Not yet recruiting
        • University of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics
        • Contact:

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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)

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

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: Investigational ultracompact OCT and OCTA system
Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece
Other Names:
  • optical coherence tomography
  • optical coherence tomography angiography
Device: retinal photographs
retinal photographs with a commercial portable bedside widefield fundus camera system
Other Names:
  • RetCam
Experimental: 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
Device: Investigational ultracompact OCT and OCTA system
Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece
Other Names:
  • optical coherence tomography
  • optical coherence tomography angiography
Experimental: 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.
Device: Investigational ultracompact OCT and OCTA system
Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece
Other Names:
  • optical coherence tomography
  • optical coherence tomography angiography
Experimental: 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.
Device: Investigational ultracompact OCT and OCTA system
Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece
Other Names:
  • optical coherence tomography
  • optical coherence tomography angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Optotype Visual acuity scores (Cohort 1 only)
Time Frame: 5-year study visit

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)
Time Frame: 4.75-year study visit
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)
Time Frame: 2-year study visit

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)
Time Frame: Up to 42 weeks post-menstrual age
Retinal thickness (microns) at the fovea and surrounding optic nerve.
Up to 42 weeks post-menstrual age
Microanatomy as measured by OCT reading
Time Frame: Up to 42 weeks post-menstrual age
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)
Time Frame: Up 42 weeks post-menstrual age
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)
Time Frame: Up to 42 weeks post-menstrual age
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)
Time Frame: Up to 42 weeks post-menstrual age
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)
Time Frame: Up to 42 weeks post-menstrual age
Based on Likert scales (1-5)
Up to 42 weeks post-menstrual age
ROP vascular severity score (Cohort 3 only)
Time Frame: Up to 42 weeks post-menstrual age
Based on a combination of relative retinal vessel tortuosity score, extraretinal neovascularization and aggressive ROP.
Up to 42 weeks post-menstrual age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)
Time Frame: 5-year study visit
Wechsler Preschool and Primary Scale of Intelligence - 4: Measures specific aspects of working memory. Each subtest produces scaled scores from 1 to 19, with average scores between 7 and 12.
5-year study visit
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)
Time Frame: 5-year study visit
Movement Assessment Battery for Children: Comprehensive measurement of motor skills & is a well-known standardized test for detecting movement difficulty in children. Higher scores reflect more motor impairment.
5-year study visit
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)
Time Frame: 5-year study visit
Developmental Test of Visual Motor Integration: Non-verbal assessment that gauges the degree to which participants can integrate visual and motor abilities. Lower scores reflect more impairment.
5-year study visit
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)
Time Frame: 5-year study visit
Child Behavior Checklist: 113 questions scored on a 3-point Likert frequency scale; scores below 93rd% are considered normal, scores 93-97th% are borderline and score above 97th% is in clinical range.
5-year study visit
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)
Time Frame: 5-year study visit
Behavior Rating Inventory of Executive Functioning: 75 items in terms of frequency on a 3-point scale; raw scores for each scale are summed and T-scores (performance score where 50 is average and standard deviation is 10 points) are used.
5-year study visit
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)
Time Frame: 5-year study visit
Social Communication Questionnaire: Total score is interpreted with a higher score in reference to cut-off (e.g. of 15) to suggest likelihood of autism spectrum.
5-year study visit

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Axial length as measured in millimeters (Cohort 1 only)
Time Frame: 4.75-year study visit
4.75-year study visit
OCT grading from commercial OCT device
Time Frame: 4.75-year study visit
Based on combination of presence or absence of retinal vessel dragging, retinal detachment and fundus pigmentation (blond, medium, dark) from ultra-widefield fundus imaging; and OCT imaging (nerve fiber layer and center foveal thickness).
4.75-year study visit
Reference standard score for ROP vascular severity (Cohort 3 only)
Time Frame: Up to 42 weeks post-menstrual age
The reference standard is the consensus determination based on a combination of OCT and photographic imaging of the relative retinal vessel tortuosity score & clinical ROP exam determination of plus, pre-plus, neither, and for all 3 assessments extraretinal neovascularization and aggressive ROP.
Up to 42 weeks post-menstrual age

Collaborators and Investigators

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

Sponsor

Duke University

Collaborators

University of Pennsylvania
National Eye Institute (NEI)

Investigators

  • Principal Investigator: Cynthia A Toth, MD, Duke University Eye Center

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)

August 16, 2021

Primary Completion (Estimated)

March 31, 2027

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

June 11, 2021

First Submitted That Met QC Criteria

August 5, 2021

First Posted (Actual)

August 6, 2021

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00107978
  • R01EY025009 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The Retinal Microanatomy in ROP Study (BabySTEPS2) data cannot be analyzed for publication until they are released by the study Principal Investigator upon final review and approval by the Data Safety and Monitoring Committee.

BabySTEPS2 data will be made available as follows:

  • A summary, de-identified data set available upon request through direct inquiries to the Study PI or Coordinating Center a year after publication.
  • By the end of the funding period, de-identified SAS data sets and form images corresponding to all data collection forms, as well as key derived variables, will be put on file with a data repository.
  • Researchers may request limited access data sets.
  • The raw and analyzed imaging datasets will be made available after the completion of the Retinal Microanatomy in ROP Study.

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.

IPD Sharing Time Frame

Data will be made available after the completion of the Retinal Microanatomy in ROP (BabySTEPS2) Study

IPD Sharing 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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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