Analyzing Retinal Microanatomy in ROP

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.

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.