Poorer neurodevelopmental outcomes associated with cystoid macular edema identified in preterm infants in the intensive care nursery

Abstract

Purpose: To evaluate the association between cystoid macular edema (CME) observed in very preterm infants and developmental outcomes at 18 to 24 months corrected age.

Design: Cohort study.

Participants: Infants born at or less than 1500 g or at or less than 30 weeks postmenstrual age who underwent screening for retinopathy of prematurity (ROP) in an intensive care nursery.

Methods: Bedside handheld spectral-domain optical coherence tomography (SD OCT; Envisu, Bioptigen, Inc, Research Triangle Park, NC) imaging was obtained from preterm infants who were being screened for ROP and graded for presence of CME, central foveal thickness (CFT), inner nuclear layer thickness, and foveal-to-parafoveal thickness ratio. At 18 to 24 months corrected age, the children were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition.

Main outcome measures: Scores on the Bayley cognitive, language, and motor subscales.

Results: Among 77 children with SD OCT imaging, 53 were evaluated with the Bayley Scales. Compared with children who did not have CME as infants (n=22), the mean score for children who had CME (n=31) was 7.3 points (95% confidence interval [CI], -15.5 to 0.9; P=0.08) lower on the cognitive subscale, 14.1 points (95% CI, -22.7 to -5.5; P=0.002) lower for the language subscale, and 11.5 points (95% CI, -21.6 to -1.3; P=0.03) lower for the motor subscale. Differences were maintained after adjusting for gestational age and birth weight. Severity of CME, as assessed by foveal-to-parafoveal thickness ratio, within the CME group correlated with poorer cognitive (R2=0.16, P=0.03) and motor (R2=0.15, P=0.03) development.

Conclusions: Cystoid macular edema observed on SD OCT in very preterm infants screened for ROP is associated with poorer language and motor skills at 18 to 24 months corrected age. Evaluation of the retina with SD-OCT may serve as an indicator of neurodevelopmental health for very preterm infants in the intensive care nursery.

Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

A, Cross-sectional spectral-domain optical coherence tomography (SD OCT) scan of the retina of a premature infant at 33 weeks postmenstrual age (PMA) and with no retinopathy of prematurity (ROP). White arrows represent central foveal thickness as well as parafoveal thickness measurements obtained at 1000 µm from the foveal center. This infant had no cystoid macular edema (CME) on SD OCT and later had relatively normal cognitive, language, and motor Bayley Scales of Infant and Toddler Development, Third Edition, scores of 100, 83, and 100, respectively, at 18 to 24 months corrected age. B, Cross-sectional SD OCT scan of the retina of a premature infant at 34 week PMA and with stage 2 ROP. White arrows represent central foveal thickness as well as parafoveal thickness measurements obtained at 1000 µm from the foveal center. This infant had severe CME on SD OCT and later had subnormal cognitive, language, and motor Bayley Scales of Infant and Toddler Development, Third Edition, scores of 60, 74, and 49, respectively, at 18 to 24 months corrected age.

Figure 2

Box-and-whisker plot showing cognitive, language, and motor Bayley Scales of Infant and Toddler Development, Third Edition, scores at 18 to 24 months corrected age for children with cystoid macular edema (CME) compared with those without CME on perinatal spectral-domain optical coherence tomography (SD OCT). The box-and-whisker plots represent the median, quartiles, maximums, and minimums of each Bayley score for each group. The wider black line represents the mean for each group. Language and motor Bayley scores were significantly lower for children with versus without CME on perinatal SD OCT imaging. There was also a trend in lower cognitive Bayley scores for infants with versus without CME on perinatal SD OCT. Relationships were maintained after adjustment for gestational age and birth weight.

Figure 3

Scatterplots showing correlation between cognitive, language, and motor Bayley Scales of Infant and Toddler Development, Third Edition, scores at 18 to 24 months corrected age and central foveal thickness (CFT), inner nuclear layer (INL) thickness, and foveal-to-parafoveal (FP) thickness ratio measured on spectral-domain optical coherence tomography (SD OCT) in 31 preterm infants with cystoid macular edema (CME). Increased FP thickness ratio on perinatal SD OCT correlated with lower cognitive and motor Bayley scores, suggesting that the severity of CME may relate to the extent of delayed neurodevelopmental outcomes.