Utility of Ultrasound and Optical Coherence Tomography in Differentiating Between Papilledema and Pseudopapilledema in Children.

BACKGROUND: Differentiating between papilledema and pseudopapilledema in children presenting with mild-to-moderate optic nerve head elevation is challenging. This study sought to determine which B-scan ultrasonography (BSUS) and optical coherence tomography (OCT) features, individually or in combination, are best able to differentiate between papilledema and pseudopapilledema in children. METHODS: Children presenting with optic nerve head elevation of unknown etiology were eligible if they underwent BSUS and OCT performed by the same investigator. The absolute optic nerve sheath diameter (in millimeter) along with the presence/absence of a hyperreflective nodule(s) at the optic nerve head (indicative of druse) from BSUS was determined. The average circumpapillary retinal nerve fiber layer (cpRNFL), diameter of Bruch membrane opening, maximum papillary height, and the presence/absence of hyper-/hyporeflective lesions at the optic nerve head were calculated. Sensitivity and specificity were calculated to evaluate which BSUS and OCT imaging features, individually and in combination, accurately classified children as having papilledema vs pseudopapilledema. RESULTS: One hundred eighty-one eyes from 94 children (mean age, 11.0 years; range, 3.2-17.9) were included; 36 eyes with papilledema and 145 eyes with pseudopapilledema. Among BSUS features, optic nerve sheath widening (>4.5 mm) demonstrated the best sensitivity (86%; 95% confidence interval [CI], 64%-96%) and specificity (88%; 95% CI, 79%-94%) for papilledema. Among OCT measures, cpRNFL thickness of ≥140 µm demonstrated the best sensitivity (83%; 95% CI, 66%-93%) and specificity (76%; 95% CI, 66%-84%) to identify papilledema. The presence of both optic nerve sheath widening (>4.5 mm) and cpRNFL thickness of ≥140 µm reduced the sensitivity (72%; 95% CI, 52%-86%) but increased specificity (95%; 95% CI, 88%-98%). CONCLUSION: BSUS (optic nerve sheath widening [>4.5 mm]) and OCT (cpRNFL thickness ≥140 µm), individually and collectively, have good diagnostic accuracy for differentiating between papilledema and pseudopapilledema. The presence of druse does not exclude the diagnosis of papilledema.

Doppler Ultrasonography of the Central Retinal Vessels in Children With Brain Death.

OBJECTIVE: The purpose of this observational study is to explore if bedside Doppler ultrasonography of the central retinal vessels has the potential to become an ancillary study to support the timely diagnosis of brain death in children. DESIGN: Seventeen-month prospective observational cohort. SETTING: Forty-four bed pediatric medical and surgical ICU in an academic teaching hospital. PATIENTS: All children 0-18 years old who were clinically evaluated for brain death at Children's National Health Systems were enrolled and followed until discharge or death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients had at least one ophthalmic ultrasound within 30 minutes of each brain death examination. The central retinal artery peak systolic blood flow velocity, resistive index, pulsatility index, and Doppler waveforms were evaluated in each patient. Thirty-five ophthalmic ultrasounds were obtained on 13 patients, 3 months to 15 years old, who each had two clinical examinations consistent with brain death. The average systolic blood pressure during the ultrasound examinations was 102 mm Hg (± 28), diastolic blood pressure 65 mm Hg (± 24), mean arterial pressure 79 mm Hg (± 23), heart rate 133 beats/min (± 27), temperature 36°C (± 0.96), arterial CO2 35 mm Hg (± 9), and end-tidal CO2 23 mm Hg (± 6). For all examinations, the average peak systolic velocity of the central retinal artery was significantly decreased at 4.66 cm/s (± 3.2). Twelve of 13 patients had both resistive indexes greater than or equal to 1, average pulsatility indexes of 3.6 (± 3.5) with transcranial Doppler waveforms consistent with brain death. Waveform analysis of the 35 ultrasound examinations revealed 11% with tall systolic peaks without diastolic flow, 17% with oscillatory flow, 29% showed short systolic spikes, and 23% had no Doppler movement detected. A rippling "tardus-parvus" waveform was present in 20% of examinations. CONCLUSION: This study supports that the combination of qualitative waveform analysis and quantitative blood flow variables of the central retinal vessels may have the potential to be developed as an ancillary study for supporting the diagnosis of brain death in children.

The Use of Ophthalmic Ultrasonography to Identify Retinal Injuries Associated With Abusive Head Trauma.

Abusive head trauma includes any nonaccidental injury inflicted to a child's head and body. It is often characterized by, but not limited to, the repetitive acceleration-deceleration forces with or without blunt head impact. It has a mortality rate of 30%, and 80% of survivors experience permanent neurologic damage. In this case series, we hypothesize that bedside ultrasonography can be useful in the identification of retinal injuries that are consistent with abusive head trauma. Ocular manifestations of abusive head trauma are identified by dilated ophthalmic examination showing retinal hemorrhages that are too numerous to count, multilayered, and extending to the periphery. Traumatic retinoschisis, splitting of the retinal layers with or without blood accumulating in the intervening space, is exclusive for abusive head trauma in infants without a history of significant cerebral crush injury. Direct visualization of intraocular structures is difficult when the eyelids are swollen shut or when dilatation must be delayed. We present a series of 11 patients with brain injuries who underwent ophthalmic point-of-care ultrasonography that revealed traumatic retinoschisis on average 60 hours earlier than direct ophthalmic visualization. Dilated ophthalmic examinations and autopsy reports confirmed retinoschisis and other forms of retinal hemorrhages that were too numerous to count, multilayered, and extending to the periphery in all 11 patients. One patient did not have a dilated ophthalmic examination; however, traumatic retinoschisis and retinal hemorrhages were confirmed on autopsy. Ocular point-of-care ultrasonography is a promising tool to investigate abusive head trauma through the identification of traumatic retinoschisis and retinal hemorrhages when pupillary dilatation and direct ophthalmic examination is delayed.

Applications of optical coherence tomography in pediatric clinical neuroscience.

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve-the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions.

Separation of outer retinal layers secondary to selumetinib.

New therapeutic agents targeting the mitogen-activated protein (MAP) kinase pathway, including MEK inhibitors, are currently being evaluated in phase 1 and 2 clinical trials for pediatric brain tumors. Ophthalmologic side effects from MEK inhibitors have previously only been reported in adults and included retinal vein occlusion, central retinal artery occlusion, and separation of the neurosensory retina. We report 2 patients with optic pathway gliomas who developed outer retinal layer separation visualized by optical coherence tomography while taking the MEK inhibitor selumetinib. After discontinuation of selumetinib, the outer retinal layer separation resolved without visual sequelae. One patient has been retreated with selumetinib and experienced recurrence of these findings.

Volume Averaging of Spectral-Domain Optical Coherence Tomography Impacts Retinal Segmentation in Children.

PURPOSE: To determine the influence of volume averaging on retinal layer thickness measures acquired with spectral-domain optical coherence tomography (SD-OCT) in children. METHODS: Macular SD-OCT images were acquired using three different volume settings (i.e., 1, 3, and 9 volumes) in children enrolled in a prospective OCT study. Total retinal thickness and five inner layers were measured around an Early Treatment Diabetic Retinopathy Scale (ETDRS) grid using beta version automated segmentation software for the Spectralis. The magnitude of manual segmentation required to correct the automated segmentation was classified as either minor (<12 lines adjusted), moderate (>12 and <25 lines adjusted), severe (>26 and <48 lines adjusted), or fail (>48 lines adjusted or could not adjust due to poor image quality). The frequency of each edit classification was assessed for each volume setting. Thickness, paired difference, and 95% limits of agreement of each anatomic quadrant were compared across volume density. RESULTS: Seventy-five subjects (median age 11.8 years, range 4.3-18.5 years) contributed 75 eyes. Less than 5% of the 9- and 3-volume scans required more than minor manual segmentation corrections, compared with 71% of 1-volume scans. The inner (3 mm) region demonstrated similar measures across all layers, regardless of volume number. The 1-volume scans demonstrated greater variability of the retinal nerve fiber layer (RNLF) thickness, compared with the other volumes in the outer (6 mm) region. CONCLUSIONS: In children, volume averaging of SD-OCT acquisitions reduce retinal layer segmentation errors. TRANSLATIONAL RELEVANCE: This study highlights the importance of volume averaging when acquiring macula volumes intended for multilayer segmentation.

Optic pathway glioma volume predicts retinal axon degeneration in neurofibromatosis type 1.

OBJECTIVE: To determine whether tumor size is associated with retinal nerve fiber layer (RNFL) thickness, a measure of axonal degeneration and an established biomarker of visual impairment in children with optic pathway gliomas (OPGs) secondary to neurofibromatosis type 1 (NF1). METHODS: Children with NF1-OPGs involving the optic nerve (extension into the chiasm and tracts permitted) who underwent both volumetric MRI analysis and optical coherence tomography (OCT) within 2 weeks of each other were included. Volumetric measurement of the entire anterior visual pathway (AVP; optic nerve, chiasm, and tract) was performed using high-resolution T1-weighted MRI. OCT measured the average RNFL thickness around the optic nerve. Linear regression models evaluated the relationship between RNFL thickness and AVP dimensions and volume. RESULTS: Thirty-eight participants contributed 55 study eyes. The mean age was 5.78 years. Twenty-two participants (58%) were female. RNFL thickness had a significant negative relationship to total AVP volume and total brain volume (p < 0.05, all comparisons). For every 1 mL increase in AVP volume, RNFL thickness declined by approximately 5 microns. A greater AVP volume of OPGs involving the optic nerve and chiasm, but not the tracts, was independently associated with a lower RNFL thickness (p < 0.05). All participants with an optic chiasm volume >1.3 mL demonstrated axonal damage (i.e., RNFL thickness <80 microns). CONCLUSIONS: Greater OPG and AVP volume predicts axonal degeneration, a biomarker of vision loss, in children with NF1-OPGs. MRI volumetric measures may help stratify the risk of visual loss from NF1-OPGs.

Reproducibility of retinal nerve fiber layer thickness measures using eye tracking in children with nonglaucomatous optic neuropathy.

PURPOSE: To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) thickness measures using eye tracking-assisted spectral-domain optical coherence tomography (SD OCT) in children with nonglaucomatous optic neuropathy. DESIGN: Prospective longitudinal study. METHODS: Circumpapillary RNFL thickness measures were acquired with SD OCT using the eye-tracking feature at 2 separate study visits. Children with normal and abnormal vision (visual acuity ≥ 0.2 logMAR above normal and/or visual field loss) who demonstrated clinical and radiographic stability were enrolled. Intra- and intervisit reproducibility was calculated for the global average and 9 anatomic sectors by calculating the coefficient of variation and intraclass correlation coefficient. RESULTS: Forty-two subjects (median age 8.6 years, range 3.9-18.2 years) met inclusion criteria and contributed 62 study eyes. Both the abnormal and normal vision cohort demonstrated the lowest intravisit coefficient of variation for the global RNFL thickness. Intervisit reproducibility remained good for those with normal and abnormal vision, although small but statistically significant increases in the coefficient of variation were observed for multiple anatomic sectors in both cohorts. The magnitude of visual acuity loss was significantly associated with the global (ß = 0.026, P < .01) and temporal sector coefficient of variation (ß = 0.099, P < .01). CONCLUSION: SD OCT with eye tracking demonstrates highly reproducible RNFL thickness measures. Subjects with vision loss demonstrate greater intra- and intervisit variability than those with normal vision.

Longitudinal Change of Circumpapillary Retinal Nerve Fiber Layer Thickness in Children With Optic Pathway Gliomas.

PURPOSE: To evaluate longitudinal changes in circumpapillary retinal nerve fiber layer (RNFL) thickness, as measured by spectral-domain optical coherence tomography (SD OCT), in children with optic pathway gliomas. DESIGN: Longitudinal cohort study. METHODS: Global and quadrant-specific circumpapillary RNFL thickness measures were acquired using either a hand-held SD OCT during sedation or a table-top SD OCT in children old enough to cooperate. Vision loss was defined as either a 0.2 logMAR decline in visual acuity or progression of visual field. Percent change in circumpapillary RNFL thickness in eyes experiencing vision loss was compared to eyes with stable vision. RESULTS: Fifty-five eyes completed 250 study visits. Ten eyes (18%) from 7 patients experienced a new episode of vision loss during the study and 45 eyes (82%) from 39 patients demonstrated stable vision across study visits. Percent decline of RNFL thickness between the baseline visit and first event of vision loss event was greatest in the superior (-14%) and inferior (-10%) quadrants as well as global average (-13%). Using a threshold of ≥10% decline in RNFL, the positive and negative predictive value for vision loss when 2 or more anatomic sectors were affected was 100% and 94%, respectively. CONCLUSIONS: Children experiencing vision loss from their optic pathway gliomas frequently demonstrate a ≥10% decline of RNFL thickness in 1 or more anatomic sectors. Global average and the inferior quadrant demonstrated the best positive and negative predictive values. Circumpapillary RNFL is a surrogate marker of vision and could be helpful in making treatment decisions for children with optic pathway gliomas.