Dynamics of Human Foveal Development after Premature Birth

Abstract

Purpose To determine the dynamic morphological development of the human fovea in-vivo utilizing portable spectral domain optical coherence tomography (SDOCT). Design Prospective, observational case series. Paticipants 31 prematurely born neonates, nine children and nine adults. Methods Sixty-two neonates were enrolled in this study. SDOCT imaging was performed after examination for retinopathy of prematurity (ROP) at the bedside in non-sedated infants ages 31-41 weeks post-menstrual-age PMA (PMA=gestational age in weeks + chronological 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. Semi-automatic retinal layer segmentation was performed. Central foveal thickness (CFT), foveal to parafoveal (FP) ratio (CFT divided by thickness 1000 μm from the foveal center), and 3D thickness maps were analyzed. Main Outcomes Measures In-vivo determination of foveal morphology, layer segmentation, analysis of sub-cellular changes, spatio-temporal layer shifting. Results In contrast to the adult fovea, we observed several signs of immaturity in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRL), 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 prior to term and minimally after that, while 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 which appeared to affect inner foveal maturation. Conclusions This study provides the first view into development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable spectral domain optical coherence tomography. 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 provide a method for mapping of foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development.

Subfoveal fluid in healthy full-term newborns observed by handheld spectral domain optical coherence tomography

“…Furthermore, previous studies reporting the SD-OCT findings of premature infants did not document this phenomenon. [4][5][6][7][8][9][10]21 Infants with bilateral subretinal fluid did not significantly differ from infants without bilateral subretinal fluid in the prevalence of persistent inner retinal layers at the foveal center, an important sign of premature retinal development [26][27][28] .…”

“…20 Maldonado and colleagues described normal macular SD-OCT findings in the eyes of a single, healthy, full term, 1-month-old newborn infant as well as 3 additional full term infants under 1 year of age. 21 The relatively low incidence (15% of infants) and transient nature (resolving within a few months) likely explains why this phenomenon has not been observed in previous SDOCT studies of full term infants.…”

Reproducibility of circumpapillary retinal nerve fiber layer measurements using handheld optical coherence tomography in sedated children

“…The development of a handheld SD-OCT has enabled pediatric practitioners to acquire high resolution images of the circumpapillary RNFL and macula in neonates, infants and young children. [13][14][15][16][17][18][19][20][21][22][23][24] While neonates and infants can be imaged while awake, the portability of the handheld OCT permits acquisition in toddlers and young children during sedation.…”

In Vivo Foveal Development Using Optical Coherence Tomography

“…4 A high-resolution (2.6 lm) handheld spectral-domain OCT (HH-SDOCT) suitable for pediatric retinal imaging has been recently developed and optimized for infants and young children. 5,6 The retinal layers identified on OCT, including the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), external limiting membrane (ELM), inner (IS) and outer (OS) segments of the photoreceptor layer, ellipsoid (ISE), contact cylinder (CC) of photoreceptors, and RPE have been correlated topographically with histology ( Fig. 1).…”