Retinal Microanatomy in Retinopathy of Prematurity (BabySTEPS2)

Official title

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

Overview

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.

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.

Interventions

• Device Investigational ultracompact OCT and OCTA system
  Handheld bedside retinal OCT and OCT angiography imaging with an investigational portable system with ultracompact handpiece
• Device retinal photographs
  retinal photographs with a commercial portable bedside widefield fundus camera system

Primary outcome measures

• Optotype Visual acuity scores (Cohort 1 only) [Time frame: 5-year study visit]
• Visual function scores (Cohort 1 only) [Time frame: 4.75-year study visit]
• Neurodevelopmental scores at 2-year study visit (Cohort 1 only) [Time frame: 2-year study visit]
• Retinal thickness at the fovea and surrounding optic nerve as measured by OCT reading (Cohort 1-3) [Time frame: Up to 42 weeks post-menstrual age]
• Microanatomy as measured by OCT reading [Time frame: Up to 42 weeks post-menstrual age]
• Microanatomy as measured by retinal photo reading (Cohort 3 only) [Time frame: Up 42 weeks post-menstrual age]
• Microanatomy as measured by clinical exam (Cohort 1-3) [Time frame: Up to 42 weeks post-menstrual age]
• Measurement of stress of imaging (Cohort 3 only) [Time frame: Up to 42 weeks post-menstrual age]
• Assessment of ease of imaging (Cohort 3 only) [Time frame: Up to 42 weeks post-menstrual age]
• ROP vascular severity score (Cohort 3 only) [Time frame: Up to 42 weeks post-menstrual age]

Secondary outcome measures (6)

• Neurodevelopmental scores at 5-year study visit (Cohort 1 only) [Time frame: 5-year study visit]
• Neurodevelopmental scores at 5-year study visit (Cohort 1 only) [Time frame: 5-year study visit]
• Neurodevelopmental scores at 5-year study visit (Cohort 1 only) [Time frame: 5-year study visit]
• Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only) [Time frame: 5-year study visit]
• Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only) [Time frame: 5-year study visit]
• Neurodevelopmental parental questionnaires at 5-year study visit (Cohort 1 only) [Time frame: 5-year study visit]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Double blind

Primary purpose

Other

Study locations

United States · 2 centers

• Duke University Eye Center — Durham
• University of Pennsylvania, Center for Preventive Ophthalmology and Biostatistics — Philadelphia

Publications

• 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. PMID 28085775
• 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. PMID 29190238
• 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. PMID 29621379
• Hsu ST, Chen X, House RJ, Kelly MP, Toth CA, Vajzovic L. Visualizing Macular Microvasculature Anomalies in 2 Infants With Treated Retinopathy of Prematurity. JAMA Ophthalmol. 2018 Dec 1;136(12):1422-1424. doi: 10.1001/jamaophthalmol.2018.3926. No abstract available. PMID 30326081
• Chen X, Mangalesh S, Dandridge A, Tran-Viet D, Wallace DK, Freedman SF, Toth CA. Spectral-Domain OCT Findings of Retinal Vascular-Avascular Junction in Infants with Retinopathy of Prematurity. Ophthalmol Retina. 2018 Sep;2(9):963-971. doi: 10.1016/j.oret.2018.02.001. Epub 2018 Mar 21. PMID 30506013
• 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. PMID 30935662
• Mangalesh S, Bleicher ID, Chen X, Viehland C, LaRocca F, Izatt JA, Freedman SF, Hartnett ME, Toth CA. Three-dimensional pattern of extraretinal neovascular development in retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2019 Apr;257(4):677-688. doi: 10.1007/s00417-019-04274-6. Epub 2019 Feb 21. PMID 30790072
• Viehland C, Chen X, Tran-Viet D, Jackson-Atogi M, Ortiz P, Waterman G, Vajzovic L, Toth CA, Izatt JA. Ergonomic handheld OCT angiography probe optimized for pediatric and supine imaging. Biomed Opt Express. 2019 Apr 29;10(5):2623-2638. doi: 10.1364/BOE.10.002623. eCollection 2019 May 1. PMID 31143506

Identifiers

NCT: NCT04995341 · Pro00107978 · R01EY025009

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗