Retinal Microanatomy in Retinopathy of Prematurity (BabySTEPS2)

Sponsor

Duke University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04995341

Collaborator

University of Pennsylvania (Other), National Eye Institute (NEI) (NIH)

236

Enrollment

Locations

Arms

55.5

Anticipated Duration (Months)

118

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Retinopathy of Prematurity	Device: Investigational ultracompact OCT and OCTA system Device: retinal photographs	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

236 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Aug 16, 2021

Anticipated Primary Completion Date :

Mar 31, 2026

Anticipated Study Completion Date :

Mar 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Functional and structural outcomes in children after bedside OCT imaging in infancy 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	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 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.	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 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 4: Adult and pediatric participants enrolled for imaging during system development 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.	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

Outcome Measures

Primary Outcome Measures

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.
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
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.
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.
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.
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)
Assessment of ease of imaging (Cohort 3 only) [Up to 42 weeks post-menstrual age]
Based on Likert scales (1-5)
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.

Secondary Outcome Measures

Neurodevelopmental scores at 5-year study visit (Cohort 1 only) [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.
Neurodevelopmental scores at 5-year study visit (Cohort 1 only) [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.
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]
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.
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only) [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.
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.

Other Outcome Measures

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]
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).
Reference standard score for ROP vascular severity (Cohort 3 only) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Eye Center	Durham	North Carolina	United States	27705
2	University of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics	Philadelphia	Pennsylvania	United States	19104