Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy

Abstract

Purpose: To detect retinal features and abnormalities on optical coherence tomography (OCT) without pupil dilation and relate these to brain injury in infants with a clinical diagnosis of hypoxic ischemic encephalopathy (HIE).

Methods: Under an institutional review board-approved protocol, we imaged eight infants without pharmacologic mydriasis, using handheld, non-contact spectral-domain (Leica Microsystems, IL) or investigational swept-source OCT at the bedside in an intensive care nursery, after birth (depending on primary clinical care team permission based on health status) and weekly until discharge. The newborn infant with HIE is neurologically unstable; therefore, pharmacologic mydriasis and stimulation with visible light for retinal examination are usually avoided. We analyzed images for retinal pathologies, central foveal thickness, and retinal nerve fiber layer (RNFL) thickness at the papillomacular bundle and compared them to historical controls and published normative data, HIE clinical assessment, and abnormalities on brain magnetic resonance imaging (MRI).

Results: On OCT, three of eight infants had bilateral multiple small macular and perimacular cystoid spaces; two of these three infants also had pronounced retinal ganglion cell layer thinning and severe brain injury on MRI and the third had bilateral paracentral acute middle maculopathy and mild brain injury on MRI. Other findings in HIE infant eyes included abnormally thin fovea and thin RNFL and markers of retinal immaturity such as the absence of sub-foveal photoreceptor development and sub-foveal fluid.

Conclusions: Bedside handheld OCT imaging within the first 2 weeks of life revealed retinal injury in infants with HIE-related brain injury. Future studies may determine the relationship between acute/subacute retinal abnormalities and brain injury severity and neurodevelopmental outcomes in HIE.

Keywords: Brain injury; HIE; Hypoxic ischemic encephalopathy; Infant; OCT; Optical coherence tomography; Paracentral acute middle maculopathy; Retina.

Figures

Figure 1:

Representative optical coherence tomography B-scans of infants with hypoxic ischemic encephalopathy (HIE) showing cystoid spaces, absence of ellipsoid zone (EZ) at the fovea (blue arrows), sub-retinal fluid (white asterisk) and ganglion cell layer (GCL) attenuation (yellow arrows) (a: 41 weeks PMA, b: 40 weeks PMA, d: 37 weeks PMA, e: 41 weeks PMA) and of preterm infants (39 weeks PMA and 41 weeks PMA) with macular edema of prematurity (MEOP) (c, f). Cystoid spaces in the inner nuclear layer were observed in only term infants with HIE (a, b, d). These spaces were either parafoveal (a, b) or foveal (d) without altering the contour of the fovea by causing a bulge. Due to complete GCL loss, the inner plexiform layer and the RNFL appear as a single layer and are not differentiated. Vinekar et al described two patterns of edema in preterm infants, pattern A that caused a central upward bulge and pattern B that did not disrupt the fovea. There was no visible central upward bulge at the fovea in HIE infants (a, b, d). When cystoid spaces involved the fovea in HIE, they bore some similarity to “pattern B” MEOP.

Figure 2:

Representative magnetic resonance imaging (MRI) T2 images, Diffusion weighted images (DWI), Apparent diffusion co-efficient (ADC) images and optical coherence tomography (OCT) B-scans of infants with varying severity of hypoxic ischemic encephalopathy. A) images of an infant (#5, 41 weeks PMA) with a brain injury score of 123; MRI images show severe loss of cortical stripe, edema, signal abnormality across the brain and the corresponding, OCT B-scan indicates loss of ganglion cell layer (GCL) and presence of parafoveal cystoid spaces (yellow arrows). B) (infant #1, 40 weeks PMA) brain injury score of 76; MRI images indicate severe injury with the white arrows pointing to normal brain, the B-scan shows GCL attenuation and presence of parafoveal cystoid spaces (yellow arrows). C) (infant # 7, 37 weeks PMA) brain injury score of 6; normal T2 image, two abnormal foci of diffusion abnormality in the frontal lobes on DWI and ADC images, OCT B-scan shows the presence of PAMM (blue double arrow) and the infant had parafoveal cystoid spaces (not represented on B-scan). D) (infant # 6, 41 weeks PMA) brain injury score 0; normal brain and retinal OCT images.