Retinal Microanatomy in Retinopathy of Prematurity (BabySTEPS2)

Not Applicable

Recruiting

• Conditions: Retinopathy of Prematurity
• Interventions: Device: Investigational ultracompact OCT and OCTA system; Device: retinal photographs

• Registration Number: NCT04995341
• Lead Sponsor: Duke University

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-06-11
• Study First Submitted QC: 2021-08-05
• Study First Posted: 2021-08-06
• Study Start: 2021-08-16
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-30
• Last Update Posted: 2024-05-31
• Primary Completion: 2026-03-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 236

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1: Functional and structural outcomes in children after bedside OCT imaging in infancy	Investigational ultracompact OCT and OCTA system	80 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
Cohort 3: Comparison of ROP imaging with investigational OCT versus retinal camera	Investigational ultracompact OCT and OCTA system	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.
Cohort 3: Comparison of ROP imaging with investigational OCT versus retinal camera	retinal photographs	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.
Cohort 4: Adult and pediatric participants enrolled for imaging during system development	Investigational ultracompact OCT and OCTA system	12 awake healthy adult controls and 12 pediatric participants undergoing examination under anesthesia in the operating room will be imaged with the investigational bedside OCT for the purpose of technological development.
Cohort 2: Test of bedside OCT imaging data to predict RW-ROP or ROP progression	Investigational ultracompact OCT and OCTA system	250 infants at risk for retinopathy of prematurity: 132 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.

Primary Outcome Measures

Name	Time	Method
Retinal thickness at the fovea and surrounding optic nerve as measured by OCT reading (Cohort 1-3)	Up to 42 weeks post-menstrual age	Retinal thickness (microns) at the fovea and surrounding optic nerve.
Assessment of ease of imaging (Cohort 3 only)	Up to 42 weeks post-menstrual age	Based on Likert scales (1-5)
Visual function scores (Cohort 1 only)	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
Optotype Visual acuity scores (Cohort 1 only)	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.
Neurodevelopmental scores at 2-year study visit (Cohort 1 only)	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.
Microanatomy as measured by OCT reading	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.
ROP vascular severity score (Cohort 3 only)	Up to 42 weeks post-menstrual age	Based on a combination of relative retinal vessel tortuosity score, extraretinal neovascularization and aggressive ROP.
Microanatomy as measured by retinal photo reading (Cohort 3 only)	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.
Microanatomy as measured by clinical exam (Cohort 1-3)	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.
Measurement of stress of imaging (Cohort 3 only)	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)

Secondary Outcome Measures

Name	Time	Method
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)	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.
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)	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.

Trial Locations

Locations (2)

Duke University Eye Center; 🇺🇸 Durham, North Carolina, United States

University of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics; 🇺🇸 Philadelphia, Pennsylvania, United States