Stimulus type and duration affect magnitude and evolution of flicker-induced hyperemia measured by laser speckle flowgraphy at the optic disc and peripapillary vessels.

Neurovascular coupling is a vital mechanism employed by the cerebrovascular system, including the eye, to regulate blood flow in periods of neuronal activation. This study aims to investigate if laser speckle flowgraphy (LSFG) can detect coupling response elicited by flickering light stimuli and how variations in stimulus type and duration can affect the magnitude and evolution of blood flow in the optic nerve head (ONH) and peripapillary vessels. Healthy adults were exposed to two types of 10-Hz flicker stimuli: a photopic negative response-like stimulus (PhNR-S) or a visual evoked potential-like stimulus (VEP-S)-each presented in separate 10- and 60-s epochs. Both PhNR-S and VEP-S significantly increased ONH blood flow (p < 0.001) immediately after flicker cessation, with a trend of 60-s stimuli (PhNR-S = 11.6%; VEP-S = 10.4%) producing a larger response than 10-s stimuli (PhNR-S = 7.5%; VEP-S = 6.2%). Moreover, exposure to 60-s stimuli elicited a significantly prolonged ONH hyperemic response, especially with PhNR-S. Lastly, stimulation with either 60-s stimuli elicited a robust increase in blood flow within the peripapillary arterioles (p < 0.01) and venules (p < 0.01) as well. Flicker stimulation with common visual electrophysiology stimuli (PhNR-S and VEP-S) induced a demonstrable increase in ONH and peripapillary vessel blood flow, which varied with flicker duration. Our results validate that LSFG is a robust method to quantify flicker-induced hyperemic responses and to study neurovascular coupling in humans.

Considering Functional Outcomes as Efficacy Endpoints in Pediatric Low-Grade Glioma Clinical Trials: An FDA Educational Symposium.

In October 2022, the FDA Oncology Center of Excellence hosted an educational symposium entitled, "Considering Functional Outcomes as Efficacy Endpoints in Pediatric Low-Grade Glioma (pLGG) Clinical Trials." The symposium brought together patient advocates, regulators from the FDA and the European Medicines Agency (EMA), and an international group of academic thought leaders in the field of pediatric neuro-oncology to discuss the potential role of functional outcomes, including visual acuity, motor function, and neurocognitive performance, as endpoints in clinical trials enrolling patients with pLGG. The panel discussed challenges and opportunities regarding the selection, implementation, and evaluation of clinical outcome assessments in these functional domains and outlined key considerations for their inclusion in future clinical trial design and role in new drug development.

Which OCT Measure of the Optic Nerve Head Improves Fastest? Towards Optimizing Early Detection of Resolving Papilledema in Children.

Purpose: Optical coherence tomography (OCT) has been used to monitor papilledema. This study aims to determine which OCT-derived measures of the optic nerve head (ONH) detect resolving papilledema in children faster than standard OCT measures. Methods: Children (≤18 years of age) with papilledema who completed optic nerve SD-OCT pretreatment and had evidence of treatment response on one or more follow-up OCTs within 4 months were included. Standard (mean circumpapillary retinal nerve fiber layer [cpRNFL] thickness), device-derived (per-quadrant cpRNFL) and custom (ONH height, maximum Bruch's membrane displacement [BMD], ONH volume [ONHV], and BMD volume) OCT measures were calculated. Per-eye generalized estimating equations (GEEs) modelled changes in device-derived and custom measures as a function of mean cpRNFL to identify those measures that resolved faster during early (0-2 months) follow-up. Mean cpRNFL coefficients of greater than 1 indicated faster resolving papilledema. Results: We included 52 eyes of 29 children (mean age, 12.8 years; 72.4% female). In analysis of early follow-up visits (38 eyes from 22 children), nasal cpRNFL and maximum BMD in each quadrant resolved faster than mean cpRNFL (GEE coefficients range, 1.14-3.37). Inferior cpRNFL, superior, nasal, and inferior ONH heights and ONHV resolved slower than mean cpRNFL (GEE coefficients range, 0.67-0.87). Conclusions: Nasal cpRNFL is a promising device-derived OCT measure for the early detection of resolving papilledema in children compared with mean cpRNFL. Maximum BMD, a custom measure, also shows promise, but its calculation has not yet been incorporated into commercial OCT devices. Translational Relevance: This study guides the optimal use of OCT in capturing resolving papilledema in children.

The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas.

BACKGROUND: Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs). METHODS: Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations. RESULTS: Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05). CONCLUSIONS: CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.

Automatic Visual Acuity Loss Prediction in Children with Optic Pathway Gliomas using Magnetic Resonance Imaging.

Children with optic pathway gliomas (OPGs), a low-grade brain tumor associated with neurofibromatosis type 1 (NF1-OPG), are at risk for permanent vision loss. While OPG size has been associated with vision loss, it is unclear how changes in size, shape, and imaging features of OPGs are associated with the likelihood of vision loss. This paper presents a fully automatic framework for accurate prediction of visual acuity loss using multi-sequence magnetic resonance images (MRIs). Our proposed framework includes a transformer-based segmentation network using transfer learning, statistical analysis of radiomic features, and a machine learning method for predicting vision loss. Our segmentation network was evaluated on multi-sequence MRIs acquired from 75 pediatric subjects with NF1-OPG and obtained an average Dice similarity coefficient of 0.791. The ability to predict vision loss was evaluated on a subset of 25 subjects with ground truth using cross-validation and achieved an average accuracy of 0.8. Analyzing multiple MRI features appear to be good indicators of vision loss, potentially permitting early treatment decisions.Clinical relevance- Accurately determining which children with NF1-OPGs are at risk and hence require preventive treatment before vision loss remains challenging, towards this we present a fully automatic deep learning-based framework for vision outcome prediction, potentially permitting early treatment decisions.

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

PURPOSE: There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). METHODS: To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. RESULTS: Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. CONCLUSION: Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.

Corrigendum: Minority influence and degrowth-oriented pro-environmental conflict: when emotions betray our attachment to the social dominant paradigm.

[This corrects the article DOI: 10.3389/fpsyg.2022.899933.].

Potential blindness from nutritional xerophthalmia in autistic patients.

BACKGROUND: Vitamin A is vital to retinal rod function and epithelial cell differentiation. Although uncommon in the developed world, vitamin A deficiency (VAD) secondary to poor diets or gastrointestinal disease has been reported and can lead to xerophthalmia, which is characterized by night blindness and a spectrum of ocular surface changes. Patients with autism spectrum disorder have been shown to have restrictive diets secondary to sensory issues leading to rejection of foods except for those of certain color or texture. METHODS: We present a case series of 6 pediatric patients with autism who developed varying degrees of xerophthalmia due to VAD, which resulted from restrictive eating. RESULTS: All patients presented with a history of eye irritation that was not relieved by antibiotic or allergy eye drops. Further questioning revealed they had restrictive diets consisting of only or mostly white and tan foods, and serum vitamin A testing confirmed severe VAD. Most stages of xerophthalmia were completely reversed with vitamin A supplementation, but in 2 patients more advanced xerophthalmia resulted in irreversible blindness and ocular damage. CONCLUSIONS: Both pediatricians and pediatric eye care providers must be vigilant for VAD as an etiology of eye irritation, photophobia, or new-onset visual impairment in autistic children. A review of the child's diet must be implemented as a standard part of routine history taken in this vulnerable population. Early identification and vitamin A supplementation can prevent irreversible ocular compromise and vision loss.

Frequency and Etiologies of Visual Disturbance After Cataract Surgery Identified in Neuro-Ophthalmology Clinics.

BACKGROUND: To identify the frequency and etiologies of visual disturbances after cataract surgery in patients referred to Neuro-ophthalmology. METHODS: This study is a retrospective chart review. Records of patients 18 years and older referred to neuro-ophthalmology clinics for new-onset visual disturbances within 6 months of cataract surgery were reviewed. Those with pre-existing neuro-ophthalmic disorders, combined intraocular procedures with cataract surgery, or inadequate follow-up were excluded. The main outcome measures were frequency and etiologies of visual disturbances after cataract surgery. Secondary analyses of a cohort of patients who had cataract surgery at our institution were performed to determine the frequency and etiology of visual disturbances after uneventful cataract surgery. RESULTS: One hundred seventy-three patients met the inclusion criteria (internal referral: 36/173, from outside surgeons: 137/173). Sixty-one percent (106/173) were newly diagnosed with neuro-ophthalmic etiologies, including 21% (36/173) with afferent and 40% (70/173) with efferent disorders. Thirty-six percent (62/173) of patients had non neuro-ophthalmic causes and 3% (5/173) had systemic conditions responsible for visual disturbances postoperatively. Decompensated strabismus causing diplopia was the most common neuro-ophthalmic diagnosis after cataract surgery (50%, 53/106). Of the 13,715 patients who had cataract surgery performed at our institution over a 9-year period, 20 of 36 patients referred for visual disturbances were identified with neuro-ophthalmic etiologies of which 85% (17/20) had postoperative diplopia. CONCLUSIONS: In our study, decompensated strabismus causing diplopia was the most common neuro-ophthalmic visual disturbance after cataract surgery. Detailed history and ocular alignment should be assessed before cataract surgery to identify patients with the risk.

Minority Influence and Degrowth-Oriented Pro-environmental Conflict: When Emotions Betray Our Attachment to the Social Dominant Paradigm.

If today the anthropogenic origin of climate change gathers almost total scientific consensus, human pro-environmental action is not changing with sufficient impact to keep global warming within the 1.5° limit. Environmental psychology has traditionally focused on the underlying barriers towards more pro-environmental behaviours. Emotions-like fear or anger-may act as such barriers especially in case of radical change (e.g., degrowth). While minority influence has been extensively applied to understand societal change, it has rarely been applied to understand the emotional responses that may hinder counter-normative pro-environmental messages. However, past literature on emotions shows that, in challenging situations-the likes of radical minority conflict-people will tend to use their emotional reaction to maintain societal status quo. Two studies investigated how participants emotionally react towards a counter-normative pro-environmental minority message (advocating degrowth). A qualitative (thematic analyses) and a quantitative (emotional self-report paradigm) studies showed that participants report emotions that allow them to realign themselves with the cultural backdrop of the social dominant paradigm (growth), thus resisting change. Specifically, although all participants tend to demonstrate higher proportions of control-oriented emotions, men do so more. These effects, as well as questions of cultural and ideological dominance, are discussed considering barriers towards pro-environmentalism.

Relating Metopic Craniosynostosis Severity to Intracranial Pressure.

PURPOSE: A subset of patients with metopic craniosynostosis are noted to have elevated intracranial pressure (ICP). However, it is not known if the propensity for elevated ICP is influenced by the severity of metopic cranial dysmorphology. METHODS: Children with nonsyndromic single-suture metopic synostosis were prospectively enrolled and underwent optical coherence tomography to measure optic nerve head morphology. Preoperative head computed tomography scans were assessed for endocranial bifrontal angle as well as scaled metopic synostosis severity score (MSS) and cranial morphology deviation score determined by CranioRate, an automated severity classifier. RESULTS: Forty-seven subjects were enrolled between 2014 and 2019, at an average age of 8.5 months at preoperative computed tomography and 11.8 months at index procedure. Fourteen patients (29.7%) had elevated optical coherence tomography parameters suggestive of elevated ICP at the time of surgery. Ten patients (21.3%) had been diagnosed with developmental delay, eight of whom demonstrated elevated ICP. There were no significant associations between measures of metopic severity and ICP. Metopic synostosis severity score and endocranial bifrontal angle were inversely correlated, as expected ( r =-0.545, P <0.001). A negative correlation was noted between MSS and formally diagnosed developmental delay ( r =-0.387, P =0.008). Likewise, negative correlations between age at procedure and both MSS and cranial morphology deviation was observed ( r =-0.573, P <0.001 and r =-0.312, P =0.025, respectively). CONCLUSIONS: Increased metopic severity was not associated with elevated ICP at the time of surgery. Patients who underwent later surgical correction showed milder phenotypic dysmorphology with an increased incidence of developmental delay.

Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation.

PURPOSE: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. METHODS: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups. RESULTS: We reached consensus on the minimal clinical and genetic criteria for diagnosing NF2 and SWN. These criteria incorporate mosaic forms of these conditions. In addition, we recommend updated nomenclature for these disorders to emphasize their phenotypic overlap and to minimize misdiagnosis with neurofibromatosis type 1. CONCLUSION: The updated criteria for NF2 and SWN incorporate clinical features and genetic testing, with a focus on using molecular data to differentiate the 2 conditions. It is likely that continued refinement of these new criteria will be necessary as investigators study the diagnostic properties of the revised criteria and identify new genes associated with SWN. In the revised nomenclature, the term "neurofibromatosis 2" has been retired to improve diagnostic specificity.

Comparison of Visual Acuity Results Between ATS-HOTV and E-ETDRS Testing Methods in Children With Optic Pathway Gliomas.

Purpose: To determine if visual acuity (VA) outcomes are comparable using the amblyopia treatment study HOTV protocol (ATS-HOTV) and electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS) protocol in children with optic pathway gliomas (OPGs). Methods: Children enrolled in a prospective study of OPGs were eligible if they completed both the ATS-HOTV and E-ETDRS during the same visit. The contribution of age, testing order, having neurofibromatosis type 1, visual field loss, and circumpapillary retinal nerve fiber layer thickness to VA difference were assessed using generalized estimating equations to account for the intereye correlation. Results: Forty-eight children (median age, 10.3 years; range, 5.2-17.1 years; 49% female) met inclusion criteria and contributed 93 study eyes at their initial visit. Eleven patients (22 eyes) had more than one study visit, permitting longitudinal evaluation. ATS-HOTV measures of VA were higher than E-ETDRS at the initial (0.13 ± 0.36 vs. 0.23 ± 0.39 logarithm of the minimum angle of resolution [logMAR], P < 0.001) and all visits (0.13 ± 0.34 vs. 0.21 ± 0.36 logMAR, P < 0.001). VA remained significantly higher with ATS-HOTV regardless of test order, but the mean difference between tests was most profound when tested with ATS-HOTV first compared to E-ETDRS first (P < 0.001). Conclusions: VA results differ significantly between the ATS-HOTV and E-ETDRS testing methods in children with OPGs. Given the wide range of ages and testing ability of children, one VA testing method should be used throughout longitudinal OPG clinical trials. Translational Relevance: It is imperative that age-appropriate VA testing methods are standardized across all pediatric OPG clinical trials.

Elevated Intracranial Pressure in Patients with Craniosynostosis by Optical Coherence Tomography.

BACKGROUND: Craniosynostosis may lead to elevated intracranial pressure, which may be implicated with impaired neurocognitive development. However, accurately measuring intracranial pressure is challenging, and patterns in craniosynostosis patients are poorly characterized. Spectral-domain optical coherence tomography may enable noninvasive assessment of intracranial pressure in pediatric patients with craniosynostosis. METHODS: Pediatric patients with craniosynostosis undergoing surgical intervention between 2014 and 2019 prospectively underwent optical coherence tomographic evaluation. Intracranial pressure was directly measured intraoperatively in a subset of cases. Optical coherence tomographic parameters were compared to directly measured intracranial pressure and used for pattern assessment. RESULTS: Optical coherence tomography was performed in 158 subjects, among which 42 underwent direct intracranial pressure measurement during an initial cranial procedure. Maximal retinal nerve fiber layer thickness, maximal retinal thickness, and maximal anterior projection optical coherence tomographic parameters were positively correlated with intracranial pressure (p ≤ 0.001), with all parameters showing significantly higher values in patients with intracranial pressure thresholds of 15 mmHg (p < 0.001) and 20 mmHg (p ≤ 0.007). Patients with maximal retinal nerve fiber layer thickness and maximal anterior projection exceeding set thresholds in optical coherence tomography of either eye demonstrated 77.3 percent sensitivity and 95.0 percent specificity for detecting intracranial pressure above 15 mmHg, and 90.0 percent sensitivity and 81.3 percent specificity for detecting intracranial pressure above 20 mmHg. Patients with associated syndromes or multiple suture involvement and patients aged 9 months or older were significantly more likely to have elevated intracranial pressure above 15 mmHg (p ≤ 0.030) and above 20 mmHg (p ≤ 0.035). CONCLUSIONS: Spectral-domain optical coherence tomography can noninvasively detect elevated intracranial pressure in patients with craniosynostosis with reliable sensitivity and specificity. This technology may help guide decisions about the appropriate type and timing of surgical treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, I.

Recovery of Vision after Optic Nerve Sheath Fenestration in Children and Adolescents with Elevated Intracranial Pressure.

PURPOSE: To evaluate the effect of optic nerve sheath fenestration (ONSF) on the recovery of visual function in pediatric patients with optic disc swelling owing to increased intracranial pressure. DESIGN: Retrospective case series. METHODS: Medical chart review of all pediatric patients who underwent ONSF between 2009 and 2020 at the Children's Hospital of Philadelphia. Visual function was assessed at pre and postoperative visits. The main outcome measures were visual acuity, color vision, extraocular motility, visual field mean deviation, retinal nerve fiber layer thickness measured by optical coherence tomography. RESULTS: Fourteen pediatric patients (10 females; mean ± SD age of 14 ± 2.6 years; range, 8.5-17.5 years) were included. Five patients underwent bilateral surgeries. Ten patients were diagnosed with idiopathic intracranial hypertension. Of the 10 idiopathic intracranial hypertension patients, 3 had a previous history of weight gain and 2 of systemic steroid treatment; these can be referred to as pseudotumor cerebri. The mean ± SD follow-up length was 16.4 ± 12.3 months. VA improved from 20/138 to 20/68 in the operated eye (P = .0003) and from 20/78 to 20/32 in the nonoperated eye (P = .02). Color vision improved in the operated eye (P = .04), extraocular motility improved in the operated and nonoperated eye (P = .002 and P = .04 respectively). Visual field mean deviation improved in the operated (-23.4 dB to -11.5 dB, P < .0001) and nonoperated eye (-19.8 dB to -6.8 dB, P = .02). Retinal nerve fiber layer thickness improved in the operated eye (349.1 to 66.2 µm; P < .0001). The postoperative improvement was observed as early as the postoperative day 1. CONCLUSIONS: ONSF produces a rapid and persistent vision improvement in both the operated eye and the nonoperated eye. In children and young adults with papilledema and elevated intracranial pressure causing vision loss that is severe at presentation or refractory to standard medical management, ONSF should be considered.

Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system.

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation.

PURPOSE: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). METHODS: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. RESULTS: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. CONCLUSION: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS.

Unicoronal Craniosynostosis: Is There a Lateral Difference in Retinal Morphology?

BACKGROUND: Craniosynostosis is the premature fusion of cranial sutures in pediatric patients, which may lead to elevated intracranial pressure due to cerebro-cephalic disproportion between a growing brain and constricted skull. It is unknown whether this increased pressure is distributed equally throughout the cranial vault, or whether certain areas of the brain experience greater pressure at these regions of premature osseous fusion. METHODS: Optical coherence tomography (OCT) is a noninvasive modality for detecting elevated intracranial pressure. Optical coherence tomography was utilized to measure the peripapillary retinal nerve fiber layer (RNFL) thickness in patients undergoing surgical correction of craniosynostosis. Retinal nerve fiber layer in the eye ipsilateral to the unicoronal suture fusion was compared to the RNFL in the eye contralateral to the unicoronal suture fusion. RESULTS: During the study interval, 21 patients met inclusion criteria. Median age at operative intervention was 8.0 months, and 28.6% patients presented with left-sided unicoronal craniosynostosis, whereas 71.4% of patients presented with right-sided unicoronal craniosynostosis. Rather than universal increase on the affected side of coronal suture fusion, retinal nerve fiber layer thickness parameters showed a rotation phenomenon, such that the patterns of elevation had a 45° circumferential rotation in the direction of intorsion. CONCLUSIONS: The explanation for these results remains elusive, but they likely indicate either intracranial changes transmitted differentially to the peripapillary retina, or differing retinal morphology, between the ipsilateral and contralateral eyes in unicoronal craniosynostosis.

Socioeconomic and Geographic Disparities in Idiopathic Intracranial Hypertension.

OBJECTIVE: To identify relationships between idiopathic intracranial hypertension (IIH) and socioeconomic determinants of health, such as low-income status and proximity to healthy food. METHODS: This retrospective case-control study of adult female neuro-ophthalmology patients from one institution identified 223 women with and 4,783 women without IIH. Street addresses were geocoded and merged with US census data to obtain census tract-level information on income and food access. Choropleth maps visualized IIH clusters within certain neighborhoods. Logistic regression compared the proportion of patients with IIH from racial and ethnic minority backgrounds, low-income census tracts, and food deserts and swamps to controls without IIH. RESULTS: In our cohort, when adjusted for age, women with IIH were more likely to be Black (odds ratio [OR] 3.96, 95% confidence interval [CI] 2.98-5.25), Hispanic (OR 2.23, 95% CI 1.14-4.36), and live in low-income tracts (OR 2.24, 95% CI 1.71-2.95) or food swamps (OR 1.54, 95% CI 1.15-2.07). Patients with IIH were less likely to live in food deserts than controls (OR 0.61, 95% CI 0.45-0.83). The association between Black race and IIH remained significant even after adjusting for other variables. CONCLUSION: IIH is more common among Black and Hispanic women than expected even when accounting for the demographics of a metropolitan city. Some of this relationship is driven by the association of obesity and IIH incidence with low income and proximity to unhealthy foods.

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.