Very Preterm Neonatal Retinal Nerve Fiber Layer Thickness is a Biomarker of Brain Anatomy and Neurodevelopmental Health

Abstract

Purpose: To assess retinal nerve fiber layer (RNFL) thickness measurements at term equivalent age (TEA, 37-42 weeks postmenstrual age, PMA) in very preterm (VPT, <32 weeks gestational age) infants and to compare these measurements to maturity, brain magnetic resonance imaging (MRI) findings, and neurodevelopment.

Methods: In a prospective cohort study, VPT infants and full term controls were imaged with handheld spectral domain optical coherence tomography (Bioptigen, Inc., Research Triangle Park, NC) in the nursery. A custom MATLAB script (Mathworks, Inc., Natick, MA) segmented the RNFL, and graders corrected segmentation and marked the fovea and optic nerve center. From these coordinates, a second script created an organizing fovea-optic nerve axis and calculated mean RNFL thickness for the papillomacular bundle (PMB), extending from -15° to +15° to the organizing axis, at a radial distance of 1.5 mm from the optic nerve center. For VPT infants, clinical brain MRI scans obtained in the nursery were scored for structural abnormalities based on scaling of Kidokoro et al. (Am J Neuroradiol, 2013, 2208-14). In addition, Bayley Scales of Infant and Toddler Development were assessed at 18-24 months corrected age, by evaluating cognitive, language, and motor skills. Expert MRI and Bayley evaluators were masked to eye imaging data. We assessed the relationships between mean RNFL thickness and Bayley scores or MRI scores using linear regression.

Results: Mean ± standard deviation RNFL thickness at the PMB was greater for term (n=50, 72 ± 13 μm) versus VPT infants (n=57, 61 ± 17 μm, P<0.001), respectively. Retinal nerve fiber layer thickness inversely correlated with MRI scores while in the nursery (signifying more extensive global lesions (n=14, R²=0.37, P=0.02)) as well as cognitive (n=29, R²=0.19, P=0.015) and motor scores (R²=0.21, P=0.009) at 18-24 months follow-up. Retinal nerve fiber layer thickness did not correlate with language scores (P=0.67).

Conclusions: Thinner RNFL at the PMB in TEA VPT infants correlates with worse cognitive and motor skills at 18-24 months corrected age and with worse abnormalities on brain MRI. Retinal nerve fiber layer thickness measured at the infant bedside provides insight into VPT infants’ brain and neurodevelopment.