Preterm infant retinal OCT markers of perinatal health and retinopathy of prematurity

Abstract

The increasing survival of preterm infants has led to the importance of improving long-term outcomes associated with preterm birth. Antenatal and perinatal insults not only impact mortality, but also long-term disability. While in the intensive care nursery, preterm infants are also exposed to various stressors that lead to long-term cognitive deficits. It is therefore critical to identify early, low-stress, non-invasive biomarkers for preterm infant health. Optical coherence tomography (OCT) is a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside with low stress relative to conventional examination. In this review we delve into discussing the associations between preterm systemic health factors and OCT-based retinal findings and their potential contribution to the development of non-invasive biomarkers for infant health and for retinopathy of prematurity (ROP).

Keywords: OCT; choroid; optical coherence tomography; perinatal systemic health; preterm infant; preterm infant retina; retinal nerve fiber layer; retinopathy of prematurity.

Figure 1

Representative handheld optical coherence tomography (OCT) serial images at the fovea (yellow star) acquired weekly from 34 weeks postmenstrual age (PMA) to 38 weeks PMA from the left eye of the same infant.

Figure 2

Handheld optical coherence tomography (OCT) imaging using (left) swept source investigational high-speed, non-contact OCT system in the intensive care nursery to image a preterm infant at the bedside. The screens are mirroring and show left-to-right: the three dimensional OCT volume, the selected cross-sectional OCT B-scan from the volume, and the en face retinal view of the scan (in which retinal vessels appear as dark lines), (Right) spectral domain commercial non-contact OCT system (Envisu 2300, Leica Microsystems) with inset showing the handheld probe being used to image a model eye.

Figure 3

Representative foveal B-scans from macular volumes from swept-source OCT systems in infants with (A,B,C) no macular edema and (D,E,F) with macular edema. (B,C,E,F) Duke OCT Retinal Analysis Program Marking Code Baby version 2.0 semiautomated segmentation at the internal limiting membrane (white), outer borders of the nerve fiber layer (magenta), inner plexiform layer (aqua), inner nuclear layer (yellow), outer plexiform layer (green), ellipsoid zone (blue; not visualized in (C) and tapering at the foveal margin in (F)), retinal pigment epithelium (inner, purple; outer, pink), and choroid (orange). Reproduced with permission from Mangalesh et al.

Figure 4

Extreme prematurity is associated with shallower foveal pits caused by thickening at the foveal center. (A) Example foveal OCT images from different infants born at a range of gestational ages (GA; columns) imaged across a range of PMA (rows). Inset numbers are the P/F ratio for the corresponding image. (B) Summary of the average maximum P/F observed per eye by GA. (C) Summary of average P/F across PMAs, excluding images with INL thickening. The study population was divided into GA quartiles for visualization. P/F is lower and increases less with PMA in more premature infants. (D) The neuroretina is thicker at the foveal center in more premature infants, and does not thin with increasing PMA. (E) Parafoveal neuroretinal thickness increases with PMA but is not affected by GA. Data displayed in this figure exclude images with INL thickening. P-values represent the results of linear mixed model analysis with gestational age treated as a continuous variable. Adapted from O'Sullivan et al.

Figure 5

(Left) Optical coherence tomography (OCT) image showing the method for measuring the central 1 mm subfoveal choroidal thickness, (middle) Box-and-whisker plots illustrating the relationship between the presence of pulmonary findings and average 1 mm subfoveal choroidal thickness, (Right) Scatterplot representing the relationship between growth velocity and average 1 mm subfoveal choroidal thickness. BPD, bronchopulmonary dysplasia; Oxygen OCT, required oxygen supplementation at the time of OCT imaging; Oxygen 36 Weeks, required oxygen supplementation at 36 weeks’ postmenstrual age; PIE, pulmonary interstitial emphysema. Adapted with permission from Michalak S et al.

Figure 6

Demonstration of the optical coherence tomography imaging probe and segmentation of retinal nerve fiber layer (RNFL). (A) The ultracompact, non-contact, handheld imaging probe being used to image an infant at the bedside in the Duke intensive care nursery. (B) Thickness map (in µm) of peripapillary RNFL derived from swept-source optical coherence tomography volumes of an eye of a preterm infant in our cohort. The white line represents the organizing axis from the optic nerve center to the fovea. The pink arc represents both temporal quadrants (arc from −45 to +45 degrees relative to the organizing axis) at 1.5 mm from the optic nerve head center. The arc between 2 dashed pink lines and arrows represents the papillomacular bundle (arc from −15 to +15 degrees relative to the organizing axis). (C) Segmentation of RNFL (between the white and pink solid lines) in the papillomacular bundle (vertical dashed pink line) in an optical coherence tomography b-scan of the same eye. Reproduced with permission from Shen LL et al.

Figure 7

Correlation between mean retinal nerve fiber layer (RNFL) thickness along the papillomacular bundle (Top) and temporal quadrant (bottom) and global brain magnetic resonance imaging (MRI) lesion burden index, white matter injury, and gray matter injury for 26 very preterm infants who underwent brain MRI while in the intensive care nursery. Thinner RNFL across either arc (papillo-macular bundle or temporal quadrant) correlated with an increase in global brain injury, white matter injury, and gray matter injury. Reproduced with permission from Rothman et al.