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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
236
Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece
retinal photographs with a commercial portable bedside widefield fundus camera system
Duke University Eye Center
Durham, North Carolina, United States
RECRUITINGUniversity of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics
Philadelphia, Pennsylvania, United States
NOT_YET_RECRUITINGOptotype Visual acuity scores (Cohort 1 only)
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.
Time frame: 5-year study visit
Visual function scores (Cohort 1 only)
Visual function at the 4.75-year visit is measured by the presence or absence of strabismus, nystagmus, and amblyopia
Time frame: 4.75-year study visit
Neurodevelopmental scores at 2-year study visit (Cohort 1 only)
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.
Time frame: 2-year study visit
Retinal thickness at the fovea and surrounding optic nerve as measured by OCT reading (Cohort 1-3)
Retinal thickness (microns) at the fovea and surrounding optic nerve.
Time frame: Up to 42 weeks post-menstrual age
Microanatomy as measured by OCT reading
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.
Time frame: Up to 42 weeks post-menstrual age
Microanatomy as measured by retinal photo reading (Cohort 3 only)
Combination of presence and severity of retinal vessel tortuosity, aggressive ROP, extra retinal neovascularization, shunt vessels, vitreous opacities, vitreous haze, retinoschisis and retinal detachment.
Time frame: Up 42 weeks post-menstrual age
Microanatomy as measured by clinical exam (Cohort 1-3)
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.
Time frame: Up to 42 weeks post-menstrual age
Measurement of stress of imaging (Cohort 3 only)
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)
Time frame: Up to 42 weeks post-menstrual age
Assessment of ease of imaging (Cohort 3 only)
Based on Likert scales (1-5)
Time frame: Up to 42 weeks post-menstrual age
ROP vascular severity score (Cohort 3 only)
Based on a combination of relative retinal vessel tortuosity score, extraretinal neovascularization and aggressive ROP.
Time frame: Up to 42 weeks post-menstrual age
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)
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.
Time frame: 5-year study visit
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)
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.
Time frame: 5-year study visit
Neurodevelopmental scores at 5-year study visit (Cohort 1 only)
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.
Time frame: 5-year study visit
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)
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.
Time frame: 5-year study visit
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)
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.
Time frame: 5-year study visit
Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only)
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.
Time frame: 5-year study visit
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