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.
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.
Study Type
OBSERVATIONAL
Enrollment
191
The swept source optical coherence tomography device was developed at Duke University as the result of collaboration between the Departments of Ophthalmology and Biomedical Engineering. The SSOCT system has a 100kHz repetition rate, 1050nm-centered swept-source light source (Axsun Technologies). This swept-source system allows near real-time OCT imaging during movement while imaging and it provides better OCT imaging of the choroid. The SSOCT system is a non-contact device and therefore does not touch the eye.
Non-sedated research brain MRI: Magnetic resonance imaging (MRI) is a minimal risk procedure that uses a magnet and radio waves to make diagnostic medical images of the body. There have been no ill effects reported from exposure to the magnetism or radio waves used in this test. However, it is possible that harmful effects could be recognized in the future. A known risk is that the magnet could attract certain kinds of metal. Therefore, we will carefully ask about metal within the body. If there is any question about potentially hazardous metal within the body, MRI imaging will not be performed. We will also keep the examining room locked so that no one carrying metal objects can enter while the child is in the scanner.
Serum/plasma (residual in the laboratory) collected as part of clinically indicated care will be shipped to the University of Florida for neuroinflammatory biomarker testing to identify central nervous system cellular injury.
University of Florida
Gainesville, Florida, United States
Washington University
St Louis, Missouri, United States
Duke University Eye Center
Durham, North Carolina, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Initiate ICN research imaging with the novel ultralight hand piece and high speed SSOCT (Aim 1A)
Start-up of research imaging in the intensive care nursery using the new ultralight hand piece and swept source OCT
Time frame: 4 years
Number of infants with reproducible imaging of the peripheral vascular-avascular junction (Aim 1B)
Analysis of reproducibility of imaging of the peripheral vascular-avascular junction in infants
Time frame: 4 years
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
Develop infant-specific automated image processing/analyses for retinal vascular imaging
Time frame: 3 months
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)
Develop infant-specific automated image processing/analyses or multi-layer segmentation
Time frame: 3 months
Retinal microanatomy grading from Swept Source Optical Coherence Tomography (SSOCT)
Grading and measurement of retinal microanatomy from SSOCT images
Time frame: 4 years
Brain MRI grading
Grading and analysis of brain MRI scans collected at approximately term-equivalent age
Time frame: 3 years
Visual acuity scores
Analyses of data from Teller Visual acuity testing at 9 months
Time frame: 3 years
Neurodevelopmental scores
Analysis of Bayley Scales-III Neurodevelopmental testing at age 2 years
Time frame: 3 years
Peripheral retinal microanatomy grading
Analyses of peripheral retinal microanatomy at the vascular-avascular junction as recorded via SSOCT
Time frame: 4 years
ROP severity grade of retinal microanatomy by OCT
Severity of ROP as determined by analysis of posterior and peripheral retinal microanatomy
Time frame: 4 years
Maximum ROP stage as determined during clinical evaluation
Analysis of maximum ROP stage per eye as determined during clinical evaluation
Time frame: 4 years
Neuroinflammatory marker scores
Analysis of left over blood samples to determine presence and severity of neuroinflammation
Time frame: 2 years
Presence of non-ROP ocular conditions
Analysis of clinical data for strabismus,, amblyopia, refractive error, nystagmus
Time frame: 4 years
ROP specifics from clinical examination
ROP specifics including zone, plus or preplus disease, stage per clock hour, vitreous hemorrhage from clinical examination
Time frame: 4 years
ROP specifics from OCT imaging
ROP specifics including zone, plus or preplus disease, stage per clock hour, vitreous hemorrhage from OCT imaging
Time frame: 4 years
Clinician's decision to treat
Analysis of the clinician's decision to treat
Time frame: 4 years
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