title: Dynamics of human foveal development after premature birth.
abstract: OBJECTIVE
  To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT).
  
  
  METHODS
  Prospective, observational case series.
  
  
  METHODS
  Thirty-one prematurely born neonates, 9 children, and 9 adults.
  
  
  METHODS
  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.
  
  
  METHODS
  In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina 27710, USA. Cynthia.toth@duke.edu
authors.forename: Ramiro S
authors.initials: RS
authors.lastname: Maldonado
authors.forename: Rachelle V
authors.initials: RV
authors.lastname: O'Connell
authors.forename: Neeru
authors.initials: N
authors.lastname: Sarin
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Freedman
authors.forename: David K
authors.initials: DK
authors.lastname: Wallace
authors.forename: C Michael
authors.initials: CM
authors.lastname: Cotten
authors.forename: Katrina P
authors.initials: KP
authors.lastname: Winter
authors.forename: Sandra
authors.initials: S
authors.lastname: Stinnett
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Chiu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Izatt
authors.forename: Sina
authors.initials: S
authors.lastname: Farsiu
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Toth
mesh_terms: D000293:Adolescent; D000328:Adult; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D005260:Female; D005584:Fovea Centralis / Q000254:growth & development*; D005865:Gestational Age; D006801:Humans; D021621:Imaging, Three-Dimensional; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D008269:Macular Edema / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D047928:Premature Birth / Q000473:pathology*; D011446:Prospective Studies; D013997:Time Factors; D041623:Tomography, Optical Coherence; D055815:Young Adult