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.

Assessment of Retinal Nerve Fiber Layer Thickness in Healthy, Full-Term Neonates

“…28–31 Our understanding of perinatal eye development and maturation has improved by comparing posterior segment microanatomy observed on SDOCT in preterm infants to that of full-term infants imaged in the nursery and further relating microanatomic abnormalities to ophthalmologic and systemic pathology. 32–40 In particular, analysis of SDOCT images allows for reproducible quantification of optic nerve head parameters as an estimate of ganglion cell axonal integrity in both full-term 32 and age-matched preterm infants. 33 Retinal nerve fiver layer thickness has previously been measured in young children with optic pathway gliomas while they were sedated for magnetic resonance imaging using a hand-held SDOCT system 5,41 and demonstrated to be reproducible.…”

Functional Outcomes of Young Infants With and Without Macular Edema

“…Infants 3, 5, 6, 9, and 11 had completed Bayley Scales of Infant and Toddler Development and were included in a previous study that related neonatal CME to neurodevelopmental outcomes. 10 The optic nerve head parameters for one infant (#6, Table 1 and 2) were part of a larger report by Tong et al 8 Demographics, maximum ROP stage, finding of plus disease, laser treatment, and age at inpatient SDOCT imaging for the 13 infants are included in Table 1. Gestational age and birth weight for these infants ranged from 24 to 39 weeks post-menstrual age (PMA) and 542 to 3380 g, respectively, and seven infants had ROP higher than stage 0 (immature retina), three of whom had laser treatment.…”

“…6,10,17,20,21 As in adult macular edema, there may be very different etiologies that produce this same anatomic event. Cystoid macular edema in two term infants with significant health problems, liver failure in one and hypopituitarism and hydrocephalus in the other, demonstrate that CME is not only associated with preterm birth.…”

“…Our knowledge of microanatomic evolution of the retina and optic nerve during the critical period of neurovascular development when infants are in the intensive care nursery has expanded due to the pioneered use of bedside spectral domain optical coherence tomography (SDOCT) in the nursery. 4-10 However, functional data regarding vision outcomes on children who had SDOCT imaging as neonates remains unreported.…”

Pediatric Optical Coherence Tomography in Clinical Practice—Recent Progress

“…5,13,23,51,[67][68][69] The presence of CME is associated with higher hyperopia and poorer neurodevelopmental and visual acuity outcomes. [70][71][72] A vascularity abnormality (VASO) score has been described that appears to be significantly higher in eyes with plus disease (Fig. 3).…”