Evaluation of optic nerve development in preterm and term infants using handheld spectral-domain optical coherence tomography

Abstract

Purpose: To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology.

Design: Prospective, cross-sectional, longitudinal study.

Participants: Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants.

Methods: We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology.

Main outcome measures: Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology.

Results: At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 μm [P<0.001] and 0.68 vs. 0.53 μm [P<0.001], respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 μm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 μm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 μm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049).

Conclusions: This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made.

Conflict of interest statement

Conflict of Interest: Dr. Toth receives royalties through her university from Alcon and research support from Bioptigen, Genentech, and Physical Sciences Inc. She also has patents pending in OCT imaging and analysis. Dr. El-Dairi received consulting fees from Prana Pharmaceuticals. No other authors have financial disclosures. No authors have a propriety interest in the current study.

Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Measurement of optic nerve parameters in a spectral domain optical coherence tomography (SDOCT) scan of an infant optic nerve. Using cross-sectional SDOCT B-scans, vertical disc diameter (vDiscDiam, dashed white line) and vertical cup diameter (vCupDiam, solid white line) were measured parallel to the anterior and posterior surface of the scan (not on the diagonal); vertical cup-to-disc ratio (vC:D) was calculated; cup depth (dotted white line) was measured parallel to the A-scans within the B-scan from the plane of the cup to the top of the lamina cribrosa (white triangles). To accommodate for image tilt in the B-scans, the plane of the disc (dashed white line) was defined as the plane halfway between the two points (white rectangles) defining Bruch’s membrane opening (BMO), which can be visualized as the outer edge of the retinal pigmented epithelium. The plane of the cup (solid white line) was defined as the plane halfway between the 2 points (gray circles) marking the cup border, set at a plane 200 μm superior to the BMO markings; the same 200 μm offset was used in the Cirrus Optic Disc Cube protocol for SDOCT. To assess the effect a change in offset between cup and disc planes would have on our measurements, we conducted secondary analyses of the same scans using 150 instead of 200 μm as the offset.

Figure 2

Comparison of optic nerve parameters in preterm (red) vs. term (blue) infants at 37–42 weeks postmenstrual age. The black line represents the adjusted mean for each group. The red (blue) box and whisker plots represent the median, quartiles, maximums and minimums of each optic nerve parameter for the preterm (term) group. Vertical cup diameter (vCupDiam) and vertical cup-to-disc ratio (vC:D) are significantly larger in preterm than in term infants. There was no significant difference in vertical disc diameter (vDiscDiam) and cup depth between the two groups. The repeat analysis with cup offset 150 μm (instead of 200 μm) above the disc plane revealed the same significant findings by term status and race (data not shown).

Figure 3

Correlation between optic nerve parameters in preterm infants at 37–42 weeks postmenstrual age (PMA) (n=23) and cognitive, language, and motor Bayley scores (Bayley Scales of Infant and Toddler Development-Third Edition). The Bayley assesses infant and toddler development across cognitive, language and motor domains, and composite standard scores can be obtained for each of these domains. These scores are based on a mean of 100 and a standard deviation of 15. Scores ranging from 85 to 115 are considered within normal limits. Mild delay is defined as a score between 85 and 70 and significant delay is defined as a score below 70.