Adam L. Rothman

Delay in retinal photoreceptor development in very preterm compared to term infants.

PURPOSE We compared photoreceptor development from spectral domain optical coherence tomography (SD-OCT) imaging in very preterm infants (VPT, <32 weeks gestational age) with those of term infants. METHODS The microanatomy of foveal SD-OCT images obtained at the bedside at 37 to 42 weeks term equivalent postmenstrual age (TEA) was reviewed with qualitative and quantitative analysis of retinal and especially photoreceptor layers in the macula. Measures of maturity included presence of the cone outer segment tips (COST) or the ellipsoid zone (EZ) at foveal center, distance from Bruchs membrane (BM) to the EZ at the foveal center, and radial distance from foveal center to first appearance of the EZ. RESULTS The incidence of the EZ developed at the foveal center was lower in VPT infants (9/64, 14%) versus term infants (22/47, 47%, P < 0.001) and lower in VPT infants with macular edema (3/46) versus VPT without edema (6/18, P = 0.01). Mean ± SD distance from the foveal center to the visible EZ was 783 ± 440 μm in VPT, and 492 ± 501 μm in term infants, P = 0.002. The height of the BM-to-EZ at the foveal center did not differ in VPT versus term infants. The COST band was not visible in any infant. CONCLUSIONS Photoreceptor inner and outer segment development in VPT infants appears delayed when compared to term infants, and the photoreceptor RPE junction remains immature in all infants at TEA. Delayed maturation of photoreceptors could contribute to differences in visual function in some VPT infants.

Evaluation of Optic Nerve Development in Preterm and Term Infants Using Handheld Spectral-Domain Optical Coherence Tomography

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.

Poorer Neurodevelopmental Outcomes Associated with Cystoid Macular Edema Identified in Preterm Infants in the Intensive Care Nursery

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.

Spectral domain optical coherence tomography characterization of pediatric epiretinal membranes.

Purpose: To compare the macular morphology of pediatric versus adult eyes with epiretinal membrane (ERM) using spectral domain optical coherence tomography and identify characteristics associated with postoperative visual acuity. Methods: This retrospective study analyzed spectral domain optical coherence tomography from pediatric subjects and a randomly selected cohort of adult subjects with ERM. Morphologic retinal and ERM features were graded by two masked spectral domain optical coherence tomography readers and compared with a postoperative change in visual acuity. Results: Pediatric ERMs (age, 0.3–16.5 years) were more confluently attached to the retina than adult ERMs (age, 40–88 years; P = 0.009) and had less fibrillary appearance of the inner retina when separation was present (P = 0.044). Pediatric ERMs were associated with more vessel dragging (P = 0.019) and less external limiting membrane (P = 0.001) and inner segment band visibility (P = 0.010), with a trend toward foveal sparing by ERM (P = 0.051) and “taco” retinal folds (P = 0.052) compared with adult eyes. Visual acuity improvement was associated with intact (P = 0.048) and smooth (P = 0.055, trend) inner segment band in children and with smooth inner segment band (P = 0.083, trend) and visible external limiting membrane (P = 0.098, trend) in adults. Conclusion: We identified morphologic differences between pediatric and adult ERM on spectral domain optical coherence tomography. Similar to adults, photoreceptor integrity with pediatric ERM seems to predict better visual acuity changes after surgical ERM removal.

FUNCTIONAL OUTCOMES OF YOUNG INFANTS WITH AND WITHOUT MACULAR EDEMA.

Purpose: The authors relate posterior segment microanatomy from perinatal spectral domain optical coherence tomography to visual acuity, brain abnormalities, and neurodevelopment. Methods: Thirteen infants (11 preterm and 2 term birth), imaged in the nursery with portable spectral domain optical coherence tomography, had visual acuity and sensorimotor testing at age 9 months to 15 months (grating acuity) or 4 years to 5 years (optotype), and medical records reviewed for brain magnetic resonance imaging reports and Bayley scales testing at age 18 months to 24 months. Results: Eight children with age-appropriate macular microanatomy without edema on perinatal spectral domain optical coherence tomography had optimal (≥20/40) or within normal limits (grating acuity) visual acuity. Five children with perinatal macular edema had suboptimal visual acuity (in 9/10 eyes) and sensorimotor deficits, magnetic resonance imaging abnormalities, or poor neurodevelopment. Macular edema persisted in 1 infant through 9-month corrected age. Conclusion: Maturation of the visual system and evolution of retinal anomalies can be monitored with posterior segment spectral domain optical coherence tomography. Retinal microanatomy observed in infancy might relate to subsequent vision and other central nervous system events, but additional studies are needed to determine the range of normal microanatomy in infants and how this relates to vision and neurodevelopment.

Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as 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. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment.

Longitudinal Follow-Up of Choroidal Thickness in Central Retinal Vein Occlusion With and Without Cystoid Macular Edema

Purpose: To investigate the longitudinal relationship between subfoveal choroidal thickness (CT) and central retinal vein occlusion (CRVO). Methods: Retrospective cohort of 104 subjects with enhanced-depth imaging optical coherence tomography for unilateral CRVO. Mean CT and best-corrected visual acuity (BCVA) were compared in eyes with and without CRVO and in eyes with CRVO with and without cystoid macular edema (CME). Results: CT was thicker in eyes with CRVO-related CME than uninvolved contralateral eyes at baseline (263.9 ± 86.9 versus 230.2 ± 87.9 µm; P < .001) and final follow-up (261.1 ± 94.7 versus 222.3 ± 86.2 µm; P = .007). CRVO eyes treated with intravitreal antivascular endothelial growth factor with or without steroid therapy showed a significant reduction in CT at final follow-up (256.3 ± 90.7 versus 236.9 ± 85.9 µm; P = .004). Subjects with CRVO who were not treated with intravitreal injections also showed a significant but more modest decline in CT over time (234.4 ± 94.2 versus 221.5 ± 97.1 µm; N = 31; P = .02). However, contralateral uninvolved eyes without CRVO did not show a significant change in CT over time (233.3 ± 87.9 versus 219.5 ± 90.6 µm; N = 71; P = .40). Persistent CME at final follow-up was associated with thicker baseline (277.6 ± 96.4 versus 235.1 ± 86.5 µm; P = .02) and final CT (265.7 ± 93.4 versus 215.0 ± 82.1 µm; P = .005). Change in CT was not related to change in BCVA (P > .05). Conclusions: CT was greater in eyes with CRVO-related CME compared to eyes with CRVO but no CME and compared to uninvolved contralateral eyes. CT decreased in eyes with CRVO over time both among eyes that received intravitreal injections and among eyes that did not receive injections. CT may be a prognosticator of treatment response in CRVO-related CME.

Optical Coherence Tomography and Wide-Field Fluorescein Angiography in Retinopathy of Prematurity

The advent and adaptation of many imaging modalities promise to revolutionize our understanding of retinopathy of prematurity (ROP) by improving the detection, diagnosis, and monitoring of response to treatment of this disease. Diagnosis and classification of ROP traditionally relies on an eye exam by an ophthalmologist expert in this area who characterizes extent and character of retinal vascularization via indirect ophthalmoscopy. Many tools now exist that allow for data acquisition by nurses, technicians, and other trained staff with the images analyzed in a more centralized location. We will focus on two rapidly evolving technologies, optical coherence tomography (OCT), and wide field fluorescein angiography (FA), to better understand how these tools may change our current understanding and management of ROP.