Dynamics of Human Foveal Development after Premature Birth

Abstract

To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT). Prospective, observational case series. Thirty-one prematurely born neonates, 9 children, and 9 adults. Sixty-two neonates were enrolled in this study. After examination for retinopathy of prematurity (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31 to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semiautomatic retinal layer segmentation was performed. Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal thickness divided by thickness 1000 μm from the foveal center), and 3-dimensional thickness maps were analyzed. In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting. In contrast with the adult fovea, several signs of immaturity were observed in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated before term and minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates that appeared to affect inner foveal maturation. This study provides the first view into the development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable SD-OCT. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity and a method for mapping foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development. Proprietary or commercial disclosure may be found after the references.