Search

Background/aims: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants., Methods: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA., Results: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 μm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 μm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 μm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 μm/week (95% CI: -0.9 to -0.6)., Conclusion: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs., Competing Interests: Competing interests: SFF: Qlaris—consultant; CT: Alcon Laboratories—royalties; EMMES—consultant; Theia Imaging—owner equity and consultant., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report optical coherence tomography (OCT) findings of cherry-red spots from Tay-Sachs and Niemann-Pick disease., Methods: Consecutive patients with Tay-Sachs and Niemann-Pick disease evaluated by the pediatric transplant and cellular therapy team, for whom a handheld OCT scan was obtained, were included. Demographic information, clinical history, fundus photography, and OCT scans were reviewed. Two masked graders evaluated each of the scans., Results: The study included 3 patients with Tay-Sachs disease (5, 8, and 14 months old) and 1 patient with Niemann-Pick disease (12 months old). All patients had bilateral cherry-red spots on fundus examination. In all patients with Tay-Sachs disease, handheld OCT revealed parafoveal ganglion cell layer (GCL) thickening, increased nerve fiber layer, and GCL reflectivity, and different levels of residual normal signal GCL. The patient with Niemann-Pick disease had similar parafoveal findings, but there was a thicker residual GCL. Sedated visual evoked potentials were unrecordable in all 4 patients despite 3 of them demonstrating normal visual behavior for age. Patients with good vision had relative sparing of the GCL on OCT., Conclusions: The cherry-red spots in lysosomal storage diseases appear as perifoveal thickening and hyperreflectivity of the GCL on OCT. In this case series, residual GCL with normal signal proved to be a better biomarker for visual function than visual evoked potentials and could be considered for future therapeutic trials. [ J Pediatr Ophthalmol Strabismus . 2023;60(6):435-440.] .

Purpose: To examine the structural changes occurring in the optic nerve head (ONH) and macula in infants with childhood glaucoma and clinically observed ONH cupping reversal following intraocular pressure (IOP)-reducing glaucoma surgery, as captured by intra-operative spectral-domain optical coherence tomography (SD-OCT)., Design: Retrospective observational case series from an ongoing prospective cohort study., Methods: Included were 18 eyes of 14 patients with childhood glaucoma. All eyes had SD-OCT imaging pre- and post-glaucoma intervention and clinically identified ONH cupping reversal. Patients with poor quality images or persistent optic nerve swelling following IOP reduction were excluded. Outcome measurements included IOP, cup-to-disc ratio, axial length and SD-OCT measurements of the peripapillary retinal nerve fiber layer (pRNFL), transverse horizontal diameter of Bruch membrane opening (BMO-D), cup depth, and macula., Results: Mean age at surgery was 1.14±0.93 years and mean interval between pre- and post-operative imaging was 127 days (range 35-595). Following intervention, mean IOP reduction was 45%, accompanied by significant reductions in the cup-to-disc ratio (0.30±0.12, p<0.001), axial length (0.43±0.28mm, p<0.001) and cup depth (46%, p<0.001). Mean global pRNFL thickness pre- vs. post-treatment was 93.1±14.7µm vs. 93.1±17.1µm, respectively, p=1.0. There was no significant difference in pre- and post-treatment global or sectoral pRNFL, 3mm macular total and segmented retinal layer volumes, or the BMO-D., Conclusions: Clinical ONH cupping reversal after IOP-lowering surgery was associated with axial length reduction and decrease in cup depth, but no significant change in the pRNFL or macular volume measures. ONH cupping reversal likely marks stabilization but any pre-intervention ONH damage persists., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Background: Giant cell arteritis (GCA) is an important diagnostic consideration in elderly patients with vision changes. Superficial temporal artery biopsy (TAB) has long been considered the gold standard diagnostic approach for GCA, but MRI has gained interest as an alternative diagnostic modality. Although most of the literature has focused on imaging abnormalities of branches of the external carotid artery, there have been a few reports of GCA-related inflammatory involvement of the orbit and internal carotid arteries (ICAs) on MRI., Methods: This was a retrospective cross-sectional study of patients undergoing TAB at a single tertiary referral center over a 5-year period. Patients who had undergone contrast-enhanced MRI of the brain and orbits within 1 month of biopsy were included. Fifty-four TAB-positive and 78 TAB-negative patients were reviewed, with the MRI studies of 7 TAB-positive and 6 TAB-negative patients deemed adequate for interpretation. MRI studies were reviewed by 2 masked neuroradiologists, and the findings were correlated with biopsy results and clinical findings., Results: Intracranial ICA vessel wall enhancement was identified in 6 of 7 TAB-positive patients (sensitivity 86%), compared with 2 of 6 TAB-negative patients (specificity 67%). Optic nerve sheath enhancement was identified in 5 of 7 TAB-positive patients (sensitivity 71%) and in 2 of 6 TAB-negative patients (specificity 67%), bilateral in all such cases. The combination of both abnormal imaging findings was observed in 5 of 7 TAB-positive patients (sensitivity 71%) and in none of the 6 TAB-negative patients (specificity 100%)., Conclusions: Intracranial ICA and optic nerve sheath enhancement were observed in a majority of patients with TAB-proven GCA, and the combination of these findings was highly specific for GCA. Identification of these abnormalities on MRI should raise concern for GCA and prompt a thorough review of systems, laboratory testing, and consideration of TAB in patients with ocular complaints potentially consistent with ischemia., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 by North American Neuro-Ophthalmology Society.)

Purpose: To assess retinal nerve fiber layer (RNFL) thickness in preterm infants., Design: Prospective observational study., Methods: We imaged 83 awake infants (159 eyes) at 36 ± 1 weeks postmenstrual age (defined as the time elapsed between the first day of the last maternal menstrual period and the time at imaging) using a handheld optical coherence tomography (OCT) system at the bedside. Blinded graders semi-automatically segmented RNFL in the papillomacular bundle (-15 to +15° relative to the fovea-optic nerve axis). We correlated RNFL thickness and 7 characteristics of interest (sex, race, ethnicity, gestational age, birth weight, stage of retinopathy at prematurity, and presence of pre-plus or plus disease) via univariable and multivariable regressions., Results: RNFL was 3.4 μm thicker in the right eyes than in the left eyes (P < .001). Among 7 characteristics, birth weight was the only independent predictor of RNFL thickness (P < .001). A 250-g increase in birth weight was associated with 5.2 μm (95% confidence interval: 3.3-7.0) increase in RNFL thickness. Compared with very preterm infants, extremely preterm infants had thinner RNFL (58.0 ± 10.7 μm vs 63.4 ± 10.7 μm, P = .03), but the statistical significance disappeared after adjustment for birth weight (P = .25). RNFL thickness was 11.2 μm thinner in extremely low birth weight infants than in very low birth weight infants (55.5 ± 8.3 μm vs. 66.7 ± 10.2 μm; P < .001). The difference remained statistically significant after adjustment for gestational age., Conclusion: Birth weight is a significant independent predictor of RNFL thickness near birth, implying that the retinal ganglion cells reserve is affected by intrauterine processes that affect birth weight., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To detect retinal features and abnormalities on optical coherence tomography (OCT) without pupil dilation and relate these to brain injury in infants with a clinical diagnosis of hypoxic ischemic encephalopathy (HIE)., Methods: Under an institutional review board-approved protocol, we imaged eight infants without pharmacologic mydriasis, using handheld, non-contact spectral-domain (Leica Microsystems, IL) or investigational swept-source OCT at the bedside in an intensive care nursery, after birth (depending on primary clinical care team permission based on health status) and weekly until discharge. The newborn infant with HIE is neurologically unstable; therefore, pharmacologic mydriasis and stimulation with visible light for retinal examination are usually avoided. We analyzed images for retinal pathologies, central foveal thickness, and retinal nerve fiber layer (RNFL) thickness at the papillomacular bundle and compared them to historical controls and published normative data, HIE clinical assessment, and abnormalities on brain magnetic resonance imaging (MRI)., Results: On OCT, three of eight infants had bilateral multiple small macular and perimacular cystoid spaces; two of these three infants also had pronounced retinal ganglion cell layer thinning and severe brain injury on MRI and the third had bilateral paracentral acute middle maculopathy and mild brain injury on MRI. Other findings in HIE infant eyes included abnormally thin fovea and thin RNFL and markers of retinal immaturity such as the absence of sub-foveal photoreceptor development and sub-foveal fluid., Conclusions: Bedside handheld OCT imaging within the first 2 weeks of life revealed retinal injury in infants with HIE-related brain injury. Future studies may determine the relationship between acute/subacute retinal abnormalities and brain injury severity and neurodevelopmental outcomes in HIE.

PRéCIS:: Overhead mounted spectral-domain optical coherence tomography (OCT) enables high-quality imaging of the optic nerve and macula in childhood glaucoma, and is particularly useful when standard tabletop OCT has failed or is not possible., Purpose: Tabletop OCT, integral to adult glaucoma management, can be limited in childhood glaucoma patients because of young age, poor cooperation, and/or technical challenges. To address these imaging difficulties, we determined the feasibility and quality of an overhead mounted unit in childhood glaucoma. Secondary aims included evaluation of peripapillary retinal nerve fiber layer (pRNFL), parafoveal total retinal thickness, and parafoveal ganglion cell complex (GCC) thickness., Materials and Methods: Children and adults with a diagnosis of childhood glaucoma were imaged with an overhead mounted spectral-domain OCT as part of a prospective cross-sectional study. Participants had poor quality or unobtainable tabletop OCT and were scheduled for an examination under anesthesia and/or surgery as part of standard care., Results: A total of 88 affected eyes in 60 of 65 (92.3%) enrolled patients (mean age, 5.9±5.9 y; range, 0.2 to 24.5) were successfully imaged. The mean image quality for analyzed scans was 22.9±6.0 dB (n=236 images). Mean values for pRNFL (80.5±31.0 µm; n=86), parafoveal total retinal thickness (301.10±39.9 µm; n=79), and parafoveal GCC thickness (96.0±21.6 µm; n=74) were calculated., Conclusions: Overhead mounted OCT allowed high-quality image acquisition and analysis in childhood glaucoma patients unable to be imaged with the tabletop counterpart, presenting an opportunity for improved clinical management and study of childhood glaucoma-related pathophysiology. pRNFL, parafoveal total retinal thickness, and parafoveal GCC thickness were decreased for affected eyes of children under 6 years of age compared with age-matched controls from a companion normative study.

Purpose: To determine the natural history and visual outcomes of papilledema in cerebral venous sinus thrombosis (CVST)., Design: Retrospective observational case series., Methods: This multicenter study included 7 tertiary care neuro-ophthalmology clinics. Sixty-five patients with CVST were identified who received serial eye examinations with documented papilledema from 2008-2016. Outcome measures included time from diagnosis to papilledema documentation, papilledema progression, time to papilledema resolution, treatment interventions and final visual outcomes., Results: Papilledema was present on initial presentation in 54% of patients or detected later during the course of the disease in 46% of patients. The average time from CVST diagnosis to papilledema documentation was 29 days with a mean (SD) initial Frisén grade of 2.7 (1.3). In 21.5% of cases, papilledema progressed over an average of 55.6 (56.6) days. Time to papilledema resolution was approximately 6 months. Final visual acuity ranged from 20/20 to light perception, with 40% of patients having residual visual field defects on standard automated perimetry. Frisén grade ≥3 (odds ratio [OR] 10.21, P < .0053) and cases with worsening papilledema (3.5, P < .043) were associated with permanent visual field deficits., Conclusions: Our study indicates the importance of serial ophthalmic evaluation in all cases of CVST. Follow-up fundoscopy is critical given that a subset of cases can show delayed onset and/or worsening of papilledema with time. Specifically, we recommend an ophthalmic examination at the time of initial diagnosis, with repeat examination within a few weeks and further follow-up depending on the level of papilledema or vision changes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Compared with fluorescein angiography (FA), the gold standard for diagnosing choroidal neovascularization (CNV) activity, optical coherence tomography angiography (OCTA) is non-invasive without risks associated with fluorescein dye use, and may be especially advantageous in the diagnosis and monitoring of children with CNV., Methods: Eight eyes from eight patients aged 12 months to 18 years were imaged with the investigational Spectralis OCTA (version 6.9, Heidelberg Engineering, Heidelberg, Germany) and the RTVue XR Avanti (Optovue Inc., Fremont, CA, USA). Two patients were imaged during examination under anesthesia while six patients were imaged in the clinic. Demographic information, ocular characteristics, treatment history, and imaging studies (color photos, fluorescein angiography, OCT) were collected and reviewed., Results: Three eyes had active CNV while five had quiescent CNV at the time of imaging. CNV was idiopathic or secondary to trauma, retinal vascular dysgenesis versus retinopathy of prematurity, pigmentary retinopathy, Best vitelliform macular dystrophy, panuveitis, morning glory disc anomaly, and optic disc drusen. OCTA of two active CNV demonstrated presence of a main trunk with multiple fine capillaries, vessel loops, and anastomoses. OCTA was repeated after treatment for two CNV and demonstrated a decrease in size with loss of fine capillaries, vessel loops, and anastomoses. For the third active CNV, OCTA verified flow in the CNV complex despite the uncertainty of FA hyperfluorescence in the setting of grossly abnormal retinal vasculature. The five quiescent CNV all lacked fine capillaries, vessel loops, and anastomoses on OCTA., Conclusion: OCTA demonstrates morphological differences between active and quiescent pediatric CNV.

Purpose: To determine reference values for the peripapillary retinal nerve fiber layer (pRNFL) and macula in children 0-5 years of age., Design: Prospective cross-sectional study., Methods: This study was set in a single large academic pediatric ophthalmology practice. Healthy, full-term children 0 to <6 years of age presenting for surgery under general anesthesia were prospectively recruited for participation. Excluded were children with systemic neurologic disease, optic nerve or retinal disease (even if unilateral) or any bilateral ocular disease process, and eyes with amblyopia, ocular disease, or spherical equivalent refractive error outside of -3.00 to +8.00 diopters. Following general anesthesia, OCT scans of the optic nerve and retina were acquired using an HRA+OCT Spectralis with Flex module (Heidelberg Engineering). Automated segmentation of the pRNFL and retinal layers was followed by manual correction., Results: Data were obtained from normal eyes of 57 participants (mean age 2.28 ± 1.50 years). Mean global pRNFL thickness was 107.6 ± 10.3 μm. Mean global pRNFL thickness was not dependent on age but showed a negative relationship with axial length (P = .01). The mean total macular volume was 8.56 ± 0.259 mm 3 (n = 38). No relationship was found between total macular volume and age. Ganglion cell layer, ganglion cell complex, and inner nuclear layer volumes showed an inverse relationship with age while the photoreceptor layers showed a logarithmic increase with age., Conclusions: Global pRNFL thickness measurements remain stable over time. Macular volume and thickness values of segmented retinal layers reflect the development of the macula with age., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess macular vasculature in healthy infants and children using OCT angiography (OCTA)., Design: Prospective cross-sectional study., Participants: One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center., Methods: We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes., Main Outcome Measures: The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC., Results: The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm 2 ; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R 2  = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R 2  = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00)., Conclusions: Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Measurements of the ganglion cell complex (GCC), comprising the retinal nerve fiber (RNFL), ganglion cell, and inner plexiform layers, can be correlated with vision loss caused by optic nerve disease. Handheld optical coherence tomography (HH-OCT) can be used with sedation in children who are not amenable to traditional imaging. We report GCC and RNFL measurements in normal children using HH-OCT., Design: Prospective observational study of normal children ≤5 years of age., Methods: Healthy, full-term children ≤5 years of age undergoing sedation or anesthesia were enrolled. Exclusion criteria included prematurity and pre-existing neurologic, genetic, metabolic, or intraocular pathology. Demographic data, axial length (Master-Vu Sonomed Escalon, Lake Success, New York, USA), and HH-OCT macular and optic nerve volume scans at 0° (Bioptigen, Inc., Morrisville, North Carolina, USA) were obtained. Retinal segmentation was completed with DOCTRAP software, creating average volume thickness maps., Results: Sixty-seven children (67 eyes, 31 males ranging in age from 3.4-70.9 months) were enrolled. Average axial length was 21.2 ± 1.0 mm with mean spherical equivalent +1.49 ± 1.34 diopters (range -2.25 to 4.25). Average GCC volume for the total retina was 0.28 ± 0.04 mm 3 . Forty-seven of these eyes had RNFL analysis. Average RNFL thickness of the papillomacular bundle was 38.2 ± 9.5 μm. There was no correlation between GCC volume, RNFL thickness, patient age, or axial length., Conclusion: Average GCC volume and RNFL thickness was stable from 6 months to 5 years of age. This study provides normative data for GCC and RNFL obtained by HH-OCT in healthy eyes of young children, to serve in evaluating those with optic neuropathies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To explore vitreoretinal pathologies and their longitudinal changes visible on handheld optical coherence tomography (OCT) of young children with familial exudative vitreoretinopathy., Methods: The authors retrospectively analyzed handheld OCT images for vitreoretinal interface and retinal abnormalities and optic nerve head (ONH) elevation., Results: From 26 eyes of 16 children (mean age 32 months) with familial exudative vitreoretinopathy, 10 had ONH dragging on photographs, and in these, handheld OCT revealed temporal and anterior retinal displacement, prominent vitreopapillary adhesion or traction, and retinal nerve fiber layer thickening at ONH margins with adjacent retinal elevation. Despite a nearly normal photographic appearance, handheld OCT revealed ONH elevation with vitreopapillary traction (6/16 eyes), ONH edema (1/16 eye), and retinal vascular protrusion (5/16 eyes). Handheld OCT-visualized vitreous abnormalities (18/26 eyes) were more prevalent at higher stages of disease. Handheld OCT-visualized elevation of ONH and the retina worsened over time in nine eyes and improved in 5/6 eyes after vitrectomy., Conclusion: Handheld OCT can detect early ONH, retinal, and vitreous changes in eyes with familial exudative vitreoretinopathy. Contraction of strongly adherent vitreous in young patients with familial exudative vitreoretinopathy appears to cause characteristic ONH dragging and tractional complications without partial posterior vitreous detachment. Vitreopapillary dragging may be visible only on OCT and may progress in the absence of obvious retinal change on conventional examination.

An investigational, portable spectral-domain optical coherence tomography (SD-OCT) unit revealed small hyperreflective opacities in both eyes of a patient with bilateral retinoblastoma. There was no evidence of vitreous seeding on ophthalmoscopy of either eye. Although the opacities may initially raise concern for potential vitreous seeding, this report suggests alternate potential etiologies for such opacities, which were also seen on imaging of a cohort of normal eyes in pediatric patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:50-52.]., (Copyright 2019, SLACK Incorporated.)

Mitochondrial dysfunction lies behind many neurodegenerative disorders, owing largely to the intense energy requirements of most neurons. Such mitochondrial dysfunction may work through a variety of mechanisms, from direct disruption of the electron transport chain to abnormal mitochondrial biogenesis. Recently, we have identified biallelic mutations in the mitochondrial flavoprotein "ferredoxin reductase" (FDXR) gene as a novel cause of mitochondriopathy, peripheral neuropathy, and optic atrophy. In this report, we expand upon those results by describing two new cases of disease-causing FDXR variants in patients with variable severity of phenotypes, including evidence of an inflammatory response in brain autopsy. To investigate the underlying pathogenesis, we examined neurodegeneration in a mouse model. We found that Fdxr mutant mouse brain tissues share pathological changes similar to those seen in patient autopsy material, including increased astrocytes. Furthermore, we show that these abnormalities are associated with increased levels of markers for both neurodegeneration and gliosis, with the latter implying inflammation as a major factor in the pathology of Fdxr mutations. These data provide further insight into the pathogenic mechanism of FDXR-mediated central neuropathy, and suggest an avenue for mechanistic studies that will ultimately inform treatment.

Purpose: To determine whether the diameter of Bruch's membrane opening (BMO) can distinguish mild papilledema from pseudopapilledema using optical coherence tomography (OCT)., Methods: The medical records of pediatric patients with pseudopapilledma due to optic nerve head (ONH) drusen, patients with papilledema, and normal control subjects were retrospectively reviewed. All eyes underwent OCT imaging of the BMO and retinal nerve fiber layer (RNFL). Transverse horizontal diameter of the BMO and papillary height were measured. Mean BMO, papillary height, and RNFL were compared and receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) and determine BMO and RNFL cut-offs for papilledema and pseudopapilledema., Results: A total of 90 eyes of 90 subjects were included: 58 with pseudopapilledema, 19 with papilledema, and 13 controls. In eyes with papilledema, mean BMO, papillary height, and RNFL decreased as papilledema resolved (1893.8 vs 1582.2 [P = 0.0003], 193.0 vs 108.9 [P < 0.0001], 893.3 vs 695.5 [P = 0.0007], resp.). Eyes with mild papilledema had greater mean BMO and RNFL than those with pseudopapilledema and controls (1893.8 vs 1541.9 vs 1628.8 [P < 0.0001, P = 0.0265] and 193.0 vs 108.7 vs 104.1 [P < 0.0001, P < 0.0001], resp.). Papillary height in mild papilledema was similar to pseudopapilledema but greater than controls (893.3 vs 863.2 vs 593.5 [P = 0.47 and P = 0.0001], resp.). ROC showed good diagnostic discrimination for BMO (AUC = 0.81; 95% CI, 0.70-0.92) and RNFL (AUC = 0.96; 95% CI, 0.93-1.0) in distinguishing mild papilledema from pseudopapilledema., Conclusions: The horizontal transverse diameter of BMO is enlarged in eyes with mild papilledema and narrows as papilledema resolves. BMO and RNFL can be used together to help distinguish mild papilledema from pseudopapilledema in children., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management.

Fulminant idiopathic intracranial hypertension (FIIH) is a subtype of idiopathic intracranial hypertension (IIH) characterized by rapid, severe, progressive vision loss. Surgical intervention is often performed either as a cerebrospinal fluid (CSF) shunt procedure or an optic nerve sheath fenestration or, at times, both. These surgical procedures carry a significant risk of morbidity and failure. We present 2 patients in whom a temporary lumbar drain was successfully used in the management of medically undertreated pediatric FIIH, and circumvented the need for surgical intervention.

Limited cooperation and attention span often lead to poorly reliable assessments of visual acuity and visual fields in children, making diagnosis and monitoring of pediatric optic neuropathies challenging. As a noninvasive imaging modality, optical coherence tomography (OCT) could offer particular utility in this patient population. OCT provides high-resolution characterization of the optic nerve head, peripapillary retinal nerve fiber layer, and cellular layers of the macula, all of which can be used to assess the severity of optic nerve disease qualitatively and quantitatively. Application of OCT to pediatric patients has been limited by technical factors and lack of pediatric normative databases, but with recent technological improvements and rapidly expanding research efforts OCT is poised to revolutionize the management of optic neuropathies in children. We review current and emerging applications of OCT to important pediatric optic neuropathies such as glaucoma, papilledema, optic neuritis, optic pathway gliomas, and congenital optic disc anomalies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nonglaucomatous cupping is commonly encountered in neuro-ophthalmic practice. However, the progression of clinical and imaging findings over time has not been well described. We present serial fundus photographs and spectral domain optical coherence tomography from a pediatric patient with neuromyelitis optic spectrum disorder, which demonstrated progression of both cupping and optic atrophy in the setting of normal intraocular pressure.

We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double vision and oscillopsia after a right fronto-temporal-orbito-zygomatic craniotomy with osteotomy of the lesser wing of the sphenoid for a complex invasive pituitary adenoma. Proptosis of the right globe was present only during mastication. Computed tomography (CT) revealed a bony defect in the right lateral orbital wall. A 48-year-old man presented with transient diplopia and scotoma in the right eye elicited by chewing. CT and magnetic resonance imaging demonstrated a bilobed lesion connecting the temporal fossa to the orbit through a defect in the right lateral orbital wall. The regional neuroanatomy and pathophysiology as pertaining to these cases are discussed.

Background: There is a paucity of literature describing risk factors for vision loss in paediatric idiopathic intracranial hypertension (IIH). We investigate the final visual function, spectral domain optical coherence tomography (SD-OCT) and enhanced depth imaging (EDI)-OCT findings in children with papilledema caused by IIH., Methods: Medical records of 31 patients with paediatric IIH (age ≤17 years) were retrospectively reviewed. Optic disc photographs on presentation and automated perimetry, SD-OCT and EDI-OCT imaging on final follow-up visit were statistically analysed to identify patient characteristics and anatomic findings associated with irreversible vision loss., Results: Permanent visual acuity or visual field loss developed in 19% of study eyes. Papilledema of modified Frisén grade ≥3 on presentation was highly predictive of permanent vision loss (p<0.001), while associations between pubertal status and visual function outcome failed to reach statistical significance. SD-OCT revealed optic atrophy in 13% and photoreceptor loss in 19% of eyes, with both findings highly associated with vision loss (p<0.0001). Optic disc drusen was noted in 48% of study eyes by EDI-OCT but was not found to be predictive of visual outcome., Conclusions: Clinical observation of high papilledema grade on presentation is predictive of poor visual outcomes. Vision loss is associated not only with optic atrophy but also with photoreceptor damage. Interestingly, a high proportion of study eyes had optic disc drusen, which was not associated with vision loss, but can be a diagnostic challenge in distinguishing true papilledema from pseudopapilledema., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To describe microcystic macular changes in patients with moderate to advanced primary open-angle glaucoma., Patients and Methods: Eleven eyes of 6 unrelated patients were retrospectively identified based on a disproportionately preserved macular thickness on optical coherence tomography (OCT) despite severe peripapillary retinal nerve fiber layer thinning. Patient demographic, history, and examination findings were reviewed., Results: All identified patients were African American, relatively young (mean age, 43.8 y) and 5 of the 6 patients were males. Examination of individual macular OCT sections through areas of disproportionately preserved macular thickness invariably demonstrated numerous small cystic cavities within the inner nuclear layer. These microcystic changes were seen in areas of the macula that corresponded with areas of glaucoma-related ganglion cell loss, therefore mimicking the normal appearance of retinal thickness in the macular region. No other retinal pathologies were identified on the macular OCT to account for these changes., Conclusions: This study describes microcystic macular changes in mostly young, African American males with moderate to advanced primary open-angle glaucoma. Vitreous adherence to the internal limiting membrane preventing retinal collapse is a proposed mechanism. The disproportionately preserved macular volume may confound the diagnosis of glaucoma in these patients.

Purpose: To evaluate the incidence of visual field defects and choroidal neovascular membranes (CNVM) in a cohort of pediatric patients with optic nerve head drusen (ONHD)., Methods: The medical records of children with ONHD seen at a single center from January 2012 to July 2014 were retrospectively reviewed to identify patients who had a dilated fundus examination, fundus photography, spectral domain optical coherence tomography (SD-OCT)/enhanced-depth imaging (EDI) of the optic nerve head (ONH), SITA fast 24-2 Humphrey visual field (HVF) testing, lumbar puncture, and ocular ultrasound. A masked neuro-ophthalmologist analyzed fundus photographs, OCT, and fields. Retinal nerve fiber layer (RNFL) data were compared to age-matched controls., Results: A total of 52 children (98 eyes) were included. Mean age was 10.8 ± 3.3 years. Of these, 42 patients had visual fields (57 eyes deemed reliable), and 19 eyes had documented visual field deficits (8 were reproducible across ≥1 sitting [frequency 14%]). After correction of plotting errors (40 eyes), RNFL thickness was 111.9 ± 17.9 μm. CNVM were present in 24 of 98 eyes (24.5%), with 21 of 24 located nasally (87.5%). Neither RNFL thinning nor identification of ONHD on fundus photography correlated with the presence of visual field defects., Conclusions: Visual field defects due to ONHD can be reliably identified in children. In eyes of children with ONHD, RNFL protocol is frequently unreliable and may overestimate RNFL thickness. EDI scans through the ONH revealed peripapillary CNVM in nearly a quarter of the patients. Further longitudinal studies looking at the progression of CNVM and visual field deficits are warranted., (Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the incidence and significance of retinal changes in pediatric eyes with glaucoma and nonglaucomatous optic atrophy by optical coherence tomography (OCT)., Design: Retrospective observational case series., Methods: OCT scans performed on children with either glaucoma or nonglaucomatous optic atrophy were retrospectively reviewed. Excluded were poor-quality scans and diagnoses of ocular hypertension or glaucoma suspects., Results: Included were 227 eyes (227 children), 151 with glaucoma and 76 with nonglaucomatous optic atrophy. Outer retinal changes were present in 20 of 151 glaucoma eyes (13.2%) (12 prior intraocular surgery, 5 uveitis, 3 primary retinopathy) and 6 of 76 nonglaucomatous optic atrophy eyes (7.9%) (1 retinal vasculitis, 3 papilledema, 2 infiltrative optic neuropathy). Excluding eyes with outer retinal changes, isolated inner nuclear layer (INL) cysts were found in 6 of 131 eyes with glaucoma (4.6%) (3 uveitis, 1 prior hydrocephalus, 1 uveitis and pars plana vitrectomy, and 1 juvenile open-angle glaucoma) and 21 of 70 eyes with nonglaucomatous optic atrophy (30%) (5 optic neuritis, 11 anterior visual pathway tumors, 2 papilledema, 3 other) (P < .0001). Compared to eyes without INL cysts, those with INL cysts had thinner average retinal nerve fiber layer (RNFL) (78.2 ± 1.8 μm vs 52.0 ± 4.8 μm, P < .0001) and worse vision (logMAR = 0.33 ± 0.04 vs 0.65 ± 0.09, P < .002)., Conclusions: INL cysts are more frequent in pediatric nonglaucomatous optic atrophy than glaucoma; they are associated with worse vision and thinner RNFL. Outer retinal changes were exclusively seen in pathology that directly affected the retina. In children, INL cysts and/or outer retinal changes without prior history of intraocular surgery or uveitis should prompt further evaluation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To assess retinal nerve fiber layer (RNFL) thickness at term-equivalent age in very preterm (<32 weeks gestational age) vs term-born infant cohorts, and compare very preterm infant RNFL thickness with brain anatomy and neurodevelopment., Design: Cohort study., Methods: RNFL was semi-automatically segmented (1 eye per infant) in 57 very preterm and 50 term infants with adequate images from bedside portable, handheld spectral-domain optical coherence tomography imaging at 37-42 weeks postmenstrual age. Mean RNFL thickness was calculated for the papillomacular bundle (-15 degrees to +15 degrees) and temporal quadrant (-45 degrees to +45 degrees) relative to the fovea-optic nerve axis. Brain magnetic resonance imaging (MRI) scans clinically obtained in 26 very preterm infants were scored for global structural abnormalities by an expert masked to data except for age. Cognitive, language, and motor skills were assessed in 33 of the very preterm infants at 18-24 months corrected age., Results: RNFL was thinner for very preterm vs term infants at the papillomacular bundle ([mean ± standard deviation] 61 ± 17 vs 72 ± 13 μm, P < .001) and temporal quadrant (72 ± 21 vs 82 ± 16 μm, P = .005). In very preterm infants, thinner papillomacular bundle RNFL correlated with higher global brain MRI lesion burden index (R(2) = 0.35, P = .001) and lower cognitive (R(2) = 0.18, P = .01) and motor (R(2) = 0.17, P = .02) scores. Relationships were similar for temporal quadrant., Conclusions: Thinner RNFL in very preterm infants relative to term-born infants may relate to brain structure and neurodevelopment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Genetically targeted therapies for rare Mendelian conditions are improving patient outcomes. Here, we present the case of a 20-mo-old female suffering from a rapidly progressing neurological disorder. Although diagnosed initially with a possible autoimmune condition, analysis of the child's exome resulted in a diagnosis of Brown-Vialetto-Van Laere syndrome 2 (BVVLS2). This new diagnosis led to a change in the therapy plan from steroids and precautionary chemotherapy to high-dose riboflavin. Improvements were reported quickly, including in motor strength after 1 mo. In this case, the correct diagnosis and appropriate treatment would have been unlikely in the absence of exome sequencing and careful interpretation. This experience adds to a growing list of examples that emphasize the importance of early genome-wide diagnostics.

One of the most promising outcomes of whole-exome sequencing (WES) is the alteration of medical management following an accurate diagnosis in patients with previously unresolved disorders. Although case reports of targeted therapies resulting from WES have been published, there are few reports with long-term follow-up that confirm a sustained therapeutic response. Following a diagnosis by WES of Brown-Vialetto-Van Laere Syndrome 2 (BVVLS2), high-dose riboflavin therapy was instituted in a 20-mo-old child. An immediate clinical response with stabilization of signs and symptoms was noted over the first 2-4 wk. Subsequent clinical follow-up over the following 8 mo demonstrates not just stabilization, but continuing and sustained improvements in all manifestations of this usually fatal condition, which generally includes worsening motor weakness, sensory ataxia, hearing, and vision impairments. This case emphasizes that early application of WES can transform patient care, enabling therapy that in addition to being lifesaving can sometimes reverse the disabling disease processes in a progressive condition.

Background: To identify clinical and laboratory factors contributing to the diagnosis of giant cell arteritis (GCA) and develop a diagnostic algorithm for the evaluation of GCA., Methods: Retrospective review of 213 consecutive cases of temporal artery biopsy (TAB) seen at a single academic center over a 10-year period (2000-2009). Pathologic specimens were re-reviewed and agreement between the original and second readings was assessed. A composite clinical suspicion score was created by adding 1 point for each of the following criteria: anterior extracranial circulation ischemia, new onset headache, abnormal laboratory results (erythrocyte sedimentation rate, C-reactive protein (CRP), or platelet count), jaw claudication, abnormal or tender superficial temporal artery, constitutional symptoms, and polymyalgia rheumatica; one point was subtracted if a comorbid condition could explain a criterion., Results: Of the 204 TABs analyzed, pathologic findings were confirmatory in 49 (24.0%) and suggestive in 12 (5.9%). TAB-positive patients were more likely to be older (age 75.2 ± 7.8 vs 69.7 ± 11.0 years, P = 0.0002), complain of jaw claudication (relative-risk = 3.26, P = 0.0014), and have thrombocytosis (relative-risk = 3.3, P = 0.0072) and elevated CRP (relative-risk = 1.8, P = 0.037). None of the patients with a clinical score less than 2 had a positive TAB. Diabetes mellitus and kidney disease were often the explanation for the symptoms and abnormal clinical finding(s) that led to a negative TAB., Conclusions: We propose a clinical algorithm that is highly predictive for a positive TAB and can be valuable in the evaluation process of suspected cases of GCA.

Background: To apply automated spectral domain optical coherence tomography (SD-OCT) segmentation to eyes with resolving papilledema., Methods: Ninety-four patients with idiopathic intracranial hypertension seen at the Duke Eye Center neuro-ophthalmology clinic between November 2010 and October 2011 were reviewed. Excluded were eyes with papilledema with Frisén grade >2, other optic neuropathies or retinopathies, and those that did not have SD-OCT imaging. The remaining 43 patients were split into 2 groups: non-atrophic papilledema and atrophic papilledema. Automated SD-OCT segmentation was performed on patients with non-atrophic papilledema and age-matched controls for each of the 9 regions of the Early Treatment Diabetic Retinopathy Study map. Bonferroni correction was used for multiple comparisons. All SD-OCT scans were reviewed for retinal structural abnormalities., Results: Total macular thickness was significantly thinner within the fovea and inner macular ring in non-atrophic papilledema vs control eyes (266 vs 276 μm, P = 0.04; 333 vs 344 μm P < 0.01, n = 26 non-atrophic papilledema, 30 controls). SD-OCT demonstrated thinning within the fovea, inner macular ring, and outer macular ring of the outer plexiform layer plus nuclear layer in non-atrophic papilledema vs control (124 vs 131 μm, P < 0.01; 112 vs 118 μm, P = 0.03; 95 vs 100 μm, P = 0.03). Retinal structural changes were seen in 21/33 eyes with atrophic papilledema vs none of the eyes with non-atrophic papilledema or controls., Conclusions: SD-OCT shows qualitative and quantitative changes in the macula of eyes with resolved papilledema.

Purpose: To evaluate a clinical observation that prepubertal children with idiopathic intracranial hypertension (IIH) have low cerebrospinal fluid (CSF) protein levels compared to healthy children and pubertal patients with IIH., Methods: The medical records of prepubertal and pubertal IIH patients and controls seen in the pediatric neuro-ophthalmology clinic at Duke between 2003 and 2013 were retrospectively reviewed. The control group consisted of children who had normal intracranial pressure on lumbar puncture performed to evaluate for headaches or anomalous-looking optic nerves. The records were analyzed with attention to demographic characteristics, clinical presentation, course, and lumbar puncture results., Results: A total of 23 prepubertal children with IIH (age range, 0.75-13 years), 16 pubertal patients with IIH (age range, 13-21 years), and 12 controls (age range 3-14 years) were included. CSF analysis revealed that prepubertal children with IIH had significantly lower CSF protein levels (17.3 ± 5.7 mg/dL) compared to pubertal subjects with IIH (23.4 ± 8.4 mg/dL; P = 0.019) or healthy controls (23.5 ± 6.4 mg/dL; P = 0.011). Furthermore, 9 of 23 prepubertal IIH patients (39%) had abnormally low CSF protein level (<15 mg/dL), compared to zero pubertal IIH patients (P = 0.005) and zero controls (P = 0.015). Acetazolamide increased CSF protein level in 100% of patients who underwent repeat lumbar puncture after starting the medication (average increase, 10.3 ± 6.6 mg/dL)., Conclusions: Low CSF protein level may have diagnostic utility as a biomarker for prepubertal IIH. Furthermore, this finding suggests that some cases of prepubertal IIH may be caused by CSF overproduction rather than decreased CSF resorption., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To measure average retinal nerve fiber layer (RNFL) thicknesses in healthy, full-term neonates., Design: Descriptive research to develop normative data., Methods: Healthy infants born between 37 and 42 weeks postmenstrual age were imaged with hand-held spectral-domain optical coherence tomography. A custom script segmented the RNFL; the fovea and optic nerve center were manually selected. A second script measured the average RNFL thickness along the papillomacular bundle, defined as the arc from -15 degrees to +15 degrees on the axis from the optic nerve to fovea, with radii of 1.1, 1.3, 1.5, and 1.7 mm from the center of the optic disc. Shapiro-Wilk W tests assessed these measurements for normality to determine the age-appropriate radial distance for subsequent analyses. Average RNFL thicknesses for four temporal 45-degree sectors (superior temporal, temporal superior, temporal inferior, and inferior temporal) and the temporal quadrant were calculated and compared to demographic parameters for all infants., Results: Fifty full-term infants were adequately imaged for RNFL analysis. RNFL thicknesses at 1.5 mm radial distance from the optic nerve were the most normally distributed. While there was a trend toward greater mean superior temporal RNFL thickness for both black and Hispanic vs white infants (128 ± 27 μm, 124 ± 30 μm, and 100 ± 19 μm, respectively, P = .04 for both comparisons), there were no other significant differences noted in RNFL thicknesses by race, sex, gestational age, or birth weight., Conclusions: We present RNFL thickness measurements for healthy, full-term infants that may serve as normative data for future analyses., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To identify optic nerve head (ONH) cupping reversal and associated optical coherence tomography (OCT) and Humphrey visual field changes in pediatric glaucoma., Design: Retrospective observational case series., Methods: Sequential surgical cases of juvenile open-angle glaucoma (OAG) or primary congenital glaucoma (PCG) with sustained postoperative intraocular pressure (IOP) reduction. Group 1 had preoperative and postoperative ONH photographs and OCT; Group 2 had preoperative clinical ONH assessment and postoperative imaging. Cupping evaluation was confirmed by masked glaucoma and neuro-ophthalmology specialists., Results: Of 80 cases, 9 eyes (9 children) met criteria for Group 1; 24 eyes (19 children) met criteria for Group 2. Group 1: Five of 9 eyes (56%) demonstrated cupping reversal, with preoperative vs postoperative mean IOP 34.2 ± 6.6 mm Hg vs 10.6 ± 4.1 mm Hg (P < .00001) and mean average retinal nerve fiber layer (RNFL) 71.0 ± 30 μm vs 62.8 ± 24 μm (P = .4), respectively. RNFL was stable in 4 of 5 eyes (all juvenile OAG), but thinned (Δ = -41 μm) in 1 eye with PCG. Humphrey visual fields (reliable in 2 of 3 eyes) showed no significant change. Group 2: Fourteen of 24 PCG eyes (58%) demonstrated cupping reversal, with preoperative vs postoperative mean IOP 36.1 ± 8.9 mm Hg vs 13.3 ± 2.1 mm Hg (P < .00001). Two eyes had thin RNFL postoperatively despite healthy-appearing ONH. Postoperative RNFL showed statistically significant linear correlation with preoperative (but not postoperative) cup-to-disc ratio. Limitations include small numbers, few reliable Humphrey visual fields, and absent preoperative imaging (Group 2)., Conclusion: Some eyes with IOP reduction and ONH cupping reversal show continued RNFL thinning postoperatively. The preoperative ONH cup-to-disc ratio predicted the postoperative RNFL better than the postoperative "reversed and smaller" cup-to-disc ratio. Cupping reversal in pediatric glaucoma may not predict improved ONH health and deserves further study., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To characterize the prevalence and features of subclinical foveal hypoplasia detected by optical coherence tomography (OCT) in children., Methods: Fast macular OCT scans were performed on normal children with normal vision for the development of a normative OCT-3 database; from this data, eyes with no discernable foveal depression were identified. When possible, the ocular imaging was repeated 3 years later using both OCT-3 and spectral domain OCT (SD-OCT). SD-OCT results were compared to age-matched controls., Results: Of the 286 normal children (mean age, 8.6 ± 3.1 years) scanned, 9 (mean age, 8 ± 2.9 years; 6 males) were found to have bilateral shallow foveal depression on OCT-3 imaging, including 8 of 154 white children (5.4%) and 1 child of mixed ethnicity (white/black). Children with shallow foveas (n = 9) had larger average foveal thickness (FT) compared to the cohort of controls (n = 277) with a defined fovea (FT = 231.4 ± 8.8 vs 188.8 ± 25.0, resp. [P < 0.0001]). Mean macular volume did not differ from that of controls. SD-OCT performed 3 years later on 5 of the 9 children with shallow foveal depression showed persistence of the inner macular layers over the foveal center, corresponding to grades 1 or 2 of foveal hypoplasia. The FT was increased compared to 5 age-matched controls with a defined fovea (FT = 294.5 ± 5.1 vs 219.75 ± 5.68 μm, resp. [P = 0.029])., Conclusions: Up to 3% of children with clinically normal eyes had an anatomically underdeveloped foveal pit bilaterally on OCT., (Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)