Clinical trial NCT02887157: Analyzing Retinal Microanatomy in ROP
Official title: Analyzing Retinal Microanatomy in Retinopathy of Prematurity to Improve Care (BabySTEPS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Retinopathy of Prematurity
Neurodevelopmental Disorders
Macular Edema
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
name: University of Pennsylvania
name: Washington University School of Medicine
name: University of Florida
First posted: 2016-09-02
Enrollment: 191
Sex: ALL
Minimum age (years): 30
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will have approximately 160 participants recruited and consented into the study at Duke University Health System. Of the 160 participants, 135 will be pediatric participants (of which 110 will be infants in the ICN) and 25 will be healthy adult volunteers. Infants in the ICN must meet the American Association of Pediatrics eligibility of ROP screening (Infants with a birth weight of ≤1500 g or gestational age of 30 weeks), and is age ≤ 34 6/7 weeks postmenstrual age at first visit.

Brief summary: Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that may impact vision in vulnerable preterm neonates for a lifetime. This study utilizes new technology to determine visual and neurological development of very preterm infants in the intensive care nursery, during a period of rapid growth of the retina, optic nerve and brain. The long-term goal of this study is to help improve preterm infant health care via objective bedside imaging and analysis that characterizes early critical indicators of poor vision, neurological development and ROP, which will rapidly translate to better early intervention and improved future vision care.

Detailed description: Retinopathy of prematurity (ROP) is a disorder of development of the neural retina and its vasculature that may impact vision in vulnerable preterm neonates for a lifetime. Clinical care of infants with ROP decreases the likelihood of blindness, but abnormal vision is common, especially in those with disease severe enough to require treatment. Because it has not been possible to distinguish whether disease and/or maldevelopment that affects specific retinal cells and/or the central nervous system (CNS) cause the vision loss, especially when it is less severe, there has been no strategy to prevent subnormal acuity in the majority of infants treated for ROP.

The interval that a preterm infant at risk for ROP spends in an intensive care nursery (ICN) is a time of rapid retinal development. Clinicians and researchers do not know how local, CNS and systemic development and disease processes are reflected in the retinal microanatomy. Abnormalities in the retina during infancy are likely early predictors of later vision problems and developmental delay. From study of preterm retinal substructures, brain anatomy, connectivity and functional networks and neuroinflammatory biomarkers this study will elucidate the pathway by which local retinal anatomic changes impact and may predict later subnormal vision and CNS function. The results of this research will enable the investigator to: distinguish ocular from non-ocular contributions to vision loss; guide future treatment directed to modify retinal anomalies such as edema; and determine which microanatomic retinal biomarkers are best to monitor effects of ROP, and effects of systemic therapies on the eye and brain. In contrast to indirect ophthalmoscopy or photography, novel non-contact ocular imaging at the bedside would enable direct telemedicine screening for ROP and for neural development in multiple nurseries.

The long-term goal is to help improve preterm infant health care via objective bedside imaging and analysis that characterizes early critical indicators of poor vision, neurological development and ROP. This will rapidly translate to early intervention and improved future vision care. Specific goals of this research are threefold: to implement technological innovations to improve optical coherence tomography (OCT) imaging in non-sedated infants in the ICN; to distinguish elements of retinal microanatomy which predict maldevelopment of visual pathway and poor neurodevelopment that may impact vision in preterm infants; and to delineate which elements and regions (posterior and peripheral) of preterm infant OCT-derived retinal microanatomy best inform us about severity of disease and visual outcomes in infants with ROP.

In addition to providing a breakthrough method for bedside analysis of the very preterm (VPT) infant posterior and peripheral retina, this study will provide the pediatric ophthalmologic and telemedicine community with methods to distinguish microanatomic markers that predict infants at risk for abnormal vision, visual pathway injury, poor functional development and progression of ROP (and combinations thereof). These biomarkers will be useful for determining ophthalmic and CNS therapeutic interventions and monitoring their impact on the visual pathway and will thus likely cross over with relevance to other infant eye and brain disease.

Eligibility criteria: Inclusion Criteria:

* Health care provider, knowledgeable of protocol, agrees that study personnel could contact the Parent/Legal Guardian
* Parent/Legal Guardian is able and willing to consent to study participation for the infant with likelihood of follow up at standard of care visits at approximately 1-month, 4-months, 9-months and 2 years corrected age
* Infant/child undergoing clinically indicated examination under anesthesia (for the testing of the custom widefield OCT lens) that may or may not have eye pathology. (Only for Aim 1)
* Infant meets the American Association of Pediatrics eligibility of ROP screening (Infants with a birth weight of ≤1500 g or gestational age of 30 weeks), and is age ≤ 34 6/7 weeks postmenstrual age at first visit
* Adults (over the age of 18 years) that may or may not have eye pathology (Only for Aim \*Participants in Aim 3 will not have a brain MRI, collection of scavenged blood for neuroinflammatory markers, or the neurodevelopmental 2-year visit.

Exclusion Criteria:

* Participant or Parent/Legal Guardian (of infant/child) 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 Peters anomaly or cataract)
* Infant has a health condition, other than prematurity, that has a profound impact on brain development (e.g. anencephaly). Note that infants with brain hemorrhages and sequelae would be eligible.

Primary outcomes:
measure: Initiate ICN research imaging with the novel ultralight hand piece and high speed SSOCT (Aim 1A)
timeFrame: 4 years
measure: Number of infants with reproducible imaging of the peripheral vascular-avascular junction (Aim 1B)
timeFrame: 4 years
measure: Number of microns of retinal thickness and distance from foveal to ellipsoid zone band as seen on retinal vascular imaging using infant specific automated image processing
timeFrame: 3 months
measure: Number of microns of retinal thickness and distance from foveal to ellipsoid zone band as seen from multi-layer segmentation using infant specific automated image processing (1C)
timeFrame: 3 months
measure: Retinal microanatomy grading from Swept Source Optical Coherence Tomography (SSOCT)
timeFrame: 4 years
measure: Brain MRI grading
timeFrame: 3 years
measure: Visual acuity scores
timeFrame: 3 years
measure: Neurodevelopmental scores
timeFrame: 3 years
measure: Peripheral retinal microanatomy grading
timeFrame: 4 years
measure: ROP severity grade of retinal microanatomy by OCT
timeFrame: 4 years
measure: Maximum ROP stage as determined during clinical evaluation
timeFrame: 4 years
Secondary outcomes:
measure: Neuroinflammatory marker scores
timeFrame: 2 years
measure: Presence of non-ROP ocular conditions
timeFrame: 4 years
measure: ROP specifics from clinical examination
timeFrame: 4 years
measure: ROP specifics from OCT imaging
timeFrame: 4 years
measure: Clinician's decision to treat
timeFrame: 4 years
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Duke Health
name: Cynthia A Toth, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Tran-Viet D, Wong BM, Mangalesh S, Maldonado R, Cotten CM, Toth CA. HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING THROUGH THE UNDILATED PUPIL IN INFANTS BORN PRETERM OR WITH HYPOXIC INJURY OR HYDROCEPHALUS. Retina. 2018 Aug;38(8):1588-1594. doi: 10.1097/IAE.0000000000001735.
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citation: 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.
citation: Ong SS, Mruthyunjaya P, Stinnett S, Vajzovic L, Toth CA. Macular Features on Spectral-Domain Optical Coherence Tomography Imaging Associated With Visual Acuity in Coats' Disease. Invest Ophthalmol Vis Sci. 2018 Jun 1;59(7):3161-3174. doi: 10.1167/iovs.18-24109.
citation: Finn AP, Chen X, Viehland C, Izatt JA, Toth CA, Vajzovic L. COMBINED INTERNAL LIMITING MEMBRANE FLAP AND AUTOLOGOUS PLASMA CONCENTRATE TO CLOSE A LARGE TRAUMATIC MACULAR HOLE IN A PEDIATRIC PATIENT. Retin Cases Brief Rep. 2021 Mar 1;15(2):107-109. doi: 10.1097/ICB.0000000000000762.
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citation: 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.
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citation: Cai CX, Go M, Kelly MP, Holgado S, Toth CA. OCULAR MANIFESTATIONS OF PORETTI-BOLTSHAUSER SYNDROME: FINDINGS FROM MULTIMODAL IMAGING AND ELECTROPHYSIOLOGY. Retin Cases Brief Rep. 2022 May 1;16(3):270-274. doi: 10.1097/ICB.0000000000000991. Epub 2020 Mar 17.
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citation: Patel PR, Imperio R, Viehland C, Tran-Viet D, Chiu SJ, Tai V, Izatt JA, Toth CA, Chen X; BabySTEPS Group. Depth-Resolved Visualization of Perifoveal Retinal Vasculature in Preterm Infants Using Handheld Optical Coherence Tomography Angiography. Transl Vis Sci Technol. 2021 Aug 2;10(9):10. doi: 10.1167/tvst.10.9.10.
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