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Heather E Moss1,2 1Department of Ophthalmology, Stanford University, Palo Alto, CA, USA; 2Department of Neurology & Neuroscience, Stanford University, Stanford, CA, USA Abstract: Multiple sclerosis (MS) is associated with vision changes both due to MS effects on visual pathways and due to medication effects on the visual pathways. Distinguishing the causes of vision change are critical to appropriate diagnosis and management. The incidence, presentation, and treatment of fingolimod-associated macular edema, alemtuzumab-associated thyroid orbitopathy, and progressive multifocal leukoencephalopathy in MS patients are reviewed. Evidence for beneficial effects of acute, chronic, and symptomatic MS medications on vision is presented. Keywords: macular edema, thyroid eye disease, optic nerve, progressive multifocal leukoencephalopathy, optic neuritis

IntroductionThere is substantial public interest in psychedelics as potential treatments for psychiatric conditions. However, most psychedelics are criminalized under federal law in the USA, so it is unclear whether use occurs with clinical support. Our objective was to assess whether naturalistic psychedelic use occurs with clinical support, interactions between those using psychedelics and healthcare providers (psychiatrist, therapist, or primary physicians), and use characteristics.MethodsWe conducted an online, anonymous, confidential, cross-sectional survey of adults reporting psychedelic use (N = 1221) through a psychedelics advocacy event and social media between 9/18/2022 and 11/5/2022. We assessed participant disclosure of psychedelic use with their psychiatric care provider (PsyCP) and/or primary care provider (PCP), desire for provider support, access to support, and rate of taking prescribed psychoactive medications alongside psychedelics.ResultsAmong participants with such care providers, 22% disclosed psychedelic use to their PCP vs. 58% to their PsyCP. Participants were less confident in PCP vs. PsyCP ability to integrate psychedelics into treatment. Common reasons for nondisclosure included stigma, inadequate provider knowledge, and legal concerns. 23% reported taking psychedelics on the same day as potentially interacting psychiatric medications (e.g., anxiolytics, antidepressants). Despite 81% of participants desiring therapist support during psychedelic experiences, only 15% had received such support.DiscussionOur results show that psychedelic use is generally disconnected from primary and psychiatric clinical care. This disconnection may result in safety issues, including inadequate screening for contraindicated conditions, lack of support during emergent adverse events, and drug interactions. Enhanced clinical education and orienting drug policy towards known harms and benefits of psychedelics is needed.

A number of studies have shown that the meanings of spoken words are activated early in processing, well before all of the word has been heard. However, these studies have not explicitly taken into account a number of variables which are known to affect word recognition processes. Two important variables are a word's imageability and its form-class. In the experiments reported here we use a cross-modal priming task to investigate the role that these variables play on the time-course with which word meanings are activated. We present visual target words for lexical decision at different points through the duration of spoken primes. In one study the spoken primes were either abstract or concrete words, and in a second they were either nouns or verbs. We found significant priming for all types of words early in the duration of a spoken prime. We discuss these results in terms of various models of semantic activation, concluding that distributed models provide the best fit to the data. [ABSTRACT FROM AUTHOR]

Presents the case of a patient with a category-specific semantic deficit for living things. Pattern of behavior of the patient; Medical history of the patient; Results of the picture naming tests; Property verification for distinctive and shared features.

Background: Administrative claims have been used to study the incidence and outcomes of nonarteritic ischemic optic neuropathy (NAION), but the validity of International Classification of Diseases (ICD)-10 codes for identifying NAION has not been examined., Methods: We identified patients at 3 academic centers who received ≥1 ICD-10 code for NAION in 2018. We abstracted the final diagnosis from clinical documentation and recorded the number of visits with an NAION diagnosis code. We calculated positive predictive value (PPV) for the overall sample and stratified by subspecialty and the number of diagnosis codes. For patients with ophthalmology or neuro-ophthalmology visit data, we recorded presenting symptoms, examination findings, and laboratory data and calculated PPV relative to case definitions of NAION that incorporated sudden onset of symptoms, optic disc edema, afferent pupillary defect, and other characteristics., Results: Among 161 patients, PPV for ≥1 ICD-10 code was 74.5% (95% CI: 67.2%-80.7%). PPV was similar when restricted to patients who had visited an ophthalmologist (75.8%, 95% CI: 68.4%-82.0%) but increased to 86.8% when restricted to those who had visited neuro-ophthalmologists (95% CI: 79.2%-91.9%). Of 113 patients with >1 ICD-10 code and complete examination data, 37 (32.7%) had documented sudden onset, optic disc swelling, and an afferent pupillary defect (95% CI: 24.7%-42.0%). Of the 76 patients who did not meet these criteria, 54 (71.0%) still received a final clinical diagnosis of NAION; for most (41/54, 75.9%), this discrepancy was due to lack of documented optic disc edema., Conclusions: The validity of ICD-10 codes for NAION in administrative claims data is high, particularly when combined with provider specialty., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Objective: Hydrocephalus is a challenging neurosurgical condition due to nonspecific symptoms and complex brain-fluid pressure dynamics. Typically, the assessment of hydrocephalus in children requires radiographic or invasive pressure monitoring. There is usually a qualitative focus on the ventricular spaces even though stress and shear forces extend across the brain. Here, the authors present an MRI-based vector approach for voxelwise brain and ventricular deformation visualization and analysis., Methods: Twenty pediatric patients (mean age 7.7 years, range 6 months-18 years; 14 males) with acute, newly diagnosed hydrocephalus requiring surgical intervention for symptomatic relief were randomly identified after retrospective chart review. Selection criteria included acquisition of both pre- and posttherapy paired 3D T1-weighted volumetric MRI (3D T1-MRI) performed on 3T MRI systems. Both pre- and posttherapy 3D T1-MRI pairs were aligned using image registration, and subsequently, voxelwise nonlinear transformations were performed to derive two exemplary visualizations of compliance: 1) a whole-brain vector map projecting the resulting deformation field on baseline axial imaging; and 2) a 3D heat map projecting the volumetric changes along ventricular boundaries and the brain periphery., Results: The patients underwent the following interventions for treatment of hydrocephalus: endoscopic third ventriculostomy (n = 6); external ventricular drain placement and/or tumor resection (n = 10); or ventriculoperitoneal shunt placement (n = 4). The mean time between pre- and postoperative imaging was 36.5 days. Following intervention, the ventricular volumes decreased significantly (mean pre- and posttherapy volumes of 151.9 cm3 and 82.0 cm3, respectively; p < 0.001, paired t-test). The largest degree of deformation vector changes occurred along the lateral ventricular spaces, relative to the genu and splenium. There was a significant correlation between change in deformation vector magnitudes within the cortical layer and age (p = 0.011, Pearson), as well as between the ventricle size and age (p = 0.014, Pearson), suggesting higher compliance among infants and younger children., Conclusions: This study highlights an approach for deformation analysis and vector mapping that may serve as a topographic visualizer for therapeutic interventions in patients with hydrocephalus. A future study that correlates the degree of cerebroventricular deformation or compliance with intracranial pressures could clarify the potential role of this technique in noninvasive pressure monitoring or in cases of noncompliant ventricles.

Objective: To review treatment modalities that have been studied in acute non arteritic anterior ischemic optic neuropathy (NAION)., Methods: We performed a comprehensive literature search of English language publications in the last 5 years, with human species and NAION. Articles were reviewed to identify those that described original research on treatment of acute NAION. Study type, setting, duration, interventions, and results were extracted and articles were reviewed for biases and limitations., Results: We identified 22 kinds of treatment varying by compound and modality. These include topical, intravitreal, and systemic drugs as well as surgical approaches. Evidence for efficacy ranges from expert opinion to randomized control trials., Conclusions: Although several treatments are utilized in practice, none of these have high quality evidence of efficacy to improve visual outcomes.  Continued collaborative research is necessary to complete high quality studies in order identify effective therapies for this rare and blinding disease., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Elevated intracranial pressure (ICP) is a serious and potentially life-threatening condition, for which clinically useful non-invasive measures have been elusive, in some cases due to their inadequate sensitivity and specificity. Our aim was to evaluate novel non-invasive ophthalmic imaging of selected pathological features seen in elevated ICP, namely peripapillary hyperreflective ovoid mass-like structures (PHOMS), peripapillary wrinkles (PPW) and retinal folds (RF) as potential biomarkers of elevated ICP., Methods: This single-center pilot study included subjects with untreated or incompletely treated high ICP. The retinas of these subjects were evaluated with averaged en-face optical coherence tomography (OCT), OCT retinal cross-sections (OCT B-scans), adaptive optics scanning light ophthalmoscopy (AOSLO), and fundus photos., Results: Seven subjects were included in the study. 6 subjects with high ICP (5 idiopathic intracranial hypertension, 1 medication induced, 30.8 ± 8.6 years, 75% female, 5 with papilledema) and 1 control (20-25 years) were included. PHOMS, PPW and RF were present in all subjects with papilledema, but neither in the high ICP subject without papilledema nor in the control subject. Averaged en-face OCT scans and AOSLO were more sensitive for PPW and RF than OCT B-scans and commercial fundus photos., Conclusion: PPW, RF and PHOMS volume have potential as non-invasive biomarkers of ICP. Novel imaging modalities may improve sensitivity. However, lack of automated image acquisition and processing limits current widespread adoption in clinical settings. Further research is needed to validate these structures as biomarkers for elevated ICP and improve clinical utility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Graven-Nielsen, Dubra, Dodd, Hamann and Moss.)

Background and Objectives: Myelin oligodendrocyte glycoprotein antibody-associated disease optic neuritis (MOGAD-ON) and nonarteritic anterior ischemic optic neuropathy (NAION) can cause acute optic neuropathy in older adults but have different managements. We aimed to determine differentiating factors between MOGAD-ON and NAION and the frequency of serum MOG-IgG false positivity among patients with NAION., Methods: In this international, multicenter, case-control study at tertiary neuro-ophthalmology centers, patients with MOGAD presenting with unilateral optic neuritis as their first attack at age 45 years or older and age-matched and sex-matched patients with NAION were included. Comorbidities, clinical presentations, acute optic disc findings, optical coherence tomography (OCT) findings, and outcomes were compared between MOGAD-ON and NAION. Multivariate analysis was performed to find statistically significant predictors of MOGAD-ON. A separate review of consecutive NAION patients seen at Mayo Clinic, Rochester, from 2018 to 2022, was conducted to estimate the frequency of false-positive MOG-IgG in this population., Results: Sixty-four patients with unilateral MOGAD-ON were compared with 64 patients with NAION. Among patients with MOGAD-ON, the median age at onset was 56 (interquartile range [IQR] 50-61) years, 70% were female, and 78% were White. Multivariate analysis showed that eye pain was strongly associated with MOGAD-ON (OR 32.905; 95% CI 2.299-473.181), while crowded optic disc (OR 0.033; 95% CI 0.002-0.492) and altitudinal visual field defect (OR 0.028; 95% CI 0.002-0.521) were strongly associated with NAION. On OCT, peripapillary retinal nerve fiber layer (pRNFL) thickness in unilateral MOGAD-ON was lower than in NAION (median 114 vs 201 μm, p < 0.001; median pRNFL thickening 25 vs 102 μm, p < 0.001). MOGAD-ON had more severe vision loss at nadir (median logMAR 1.0 vs 0.3, p < 0.001), but better recovery (median logMAR 0.1 vs 0.3, p = 0.002). In the cohort of consecutive NAION patients, 66/212 (31%) patients with NAION were tested for MOG-IgG and 8% (95% CI 1%-14%) of those had false-positive serum MOG-IgG at low titers., Discussion: Acute unilateral optic neuropathy with optic disc edema in older adults can be caused by either MOGAD-ON or NAION. Detailed history, the degree of pRNFL swelling on OCT, and visual outcomes can help differentiate the entities and prevent indiscriminate serum MOG-IgG testing in all patients with acute optic neuropathy.

Background: While large language models (LLMs) are increasingly used in medicine, their effectiveness compared with human experts remains unclear. This study evaluates the quality and empathy of Expert + AI, human experts, and LLM responses in neuro-ophthalmology., Methods: This randomized, masked, multicenter cross-sectional study was conducted from June to July 2023. We randomly assigned 21 neuro-ophthalmology questions to 13 experts. Each expert provided an answer and then edited a ChatGPT-4-generated response, timing both tasks. In addition, 5 LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, Bard) generated responses. Anonymized and randomized responses from Expert + AI, human experts, and LLMs were evaluated by the remaining 12 experts. The main outcome was the mean score for quality and empathy, rated on a 1-5 scale., Results: Significant differences existed between response types for both quality and empathy (P < 0.0001, P < 0.0001). For quality, Expert + AI (4.16 ± 0.81) performed the best, followed by GPT-4 (4.04 ± 0.92), GPT-3.5 (3.99 ± 0.87), Claude (3.6 ± 1.09), Expert (3.56 ± 1.01), Bard (3.5 ± 1.15), and Bing (3.04 ± 1.12). For empathy, Expert + AI (3.63 ± 0.87) had the highest score, followed by GPT-4 (3.6 ± 0.88), Bard (3.54 ± 0.89), GPT-3.5 (3.5 ± 0.83), Bing (3.27 ± 1.03), Expert (3.26 ± 1.08), and Claude (3.11 ± 0.78). For quality (P < 0.0001) and empathy (P = 0.002), Expert + AI performed better than Expert. Time taken for expert-created and expert-edited LLM responses was similar (P = 0.75)., Conclusions: Expert-edited LLM responses had the highest expert-determined ratings of quality and empathy warranting further exploration of their potential benefits in clinical settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 North American Neuro-Ophthalmology Society.)

Importance: The American Academy of Neurology Axon Registry® provides real-world data for patients with multiple sclerosis and neuro-myelitis optica. However, some data are incomplete (e.g. demographics) and some relevant outcomes are not systematically captured in neurology documentation (e.g. visual acuity). The American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) contains demographic and visual function data that may complement Axon Registry-derived data to enhance understanding of real-world visual outcomes in neurological disease., Objective: To combine Axon Registry and IRIS Registry data to reduce missingness of demographic information and characterize visual outcomes in patients with multiple sclerosis and neuro-myelitis optica., Design: Cross-sectional study., Setting: Outpatient neurology and ophthalmology clinical practices., Participants: Patients participating in both registries between January 1, 2014 through December 10, 2021 were included if they had repeat ICD-9/10 codes for with multiple sclerosis or neuro-myelitis optica in the Axon registry., Exposure: Diagnosis (multiple sclerosis or neuro-myelitis optica)., Main Outcome and Measure: Age, sex, race and ethnicity were assessed in the individual registries and classified as conflicting, missing, or not missing in the combined data set. The IRIS Registry contributed visual acuity data., Results: Among 60,316 patients with multiple sclerosis and 1,068 patients with neuro-myelitis optica in the Axon Registry, 14,085 and 252 had temporal overlap in the IRIS Registry. Combining data reduced missing or conflicting data for race and ethnicity by 15-19 % (absolute reduction, all p ≤ 0.0005), but not age (p = 1.0) or gender (p = 0.08). 10,907 patients with MS and 142 with NMO had visual acuity data in the IRIS Registry. Visual acuity averaged between eyes was worse in patients with NMO after adjusting for age and gender (0.17 logMAR, 95 %CI 0.12,0.21, p < 0.0005)., Conclusion and Relevance: Using data from two registries reduced missing data for race and ethnicity and enabled examination of outcomes captured in the IRIS Registry for conditions that are diagnosed more frequently in the Axon Registry, demonstrating the utility of a multi-registry analysis., Competing Interests: Declaration of competing interest All authors were employees or consultants for Verana Health at the time of study performance., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Purpose: To compare disparities in outpatient ophthalmic care during early and later periods of the COVID-19 public health emergency., Methods: This cross-sectional study compared non-peri-operative outpatient ophthalmology visits by unique patients at an adult ophthalmology practice affiliated with a tertiary-care academic medical center in the Western US during three time periods: pre-COVID (3/15/19-4/15/19), early-COVID (3/15/20-4/15/20), and late-COVID (3/15/21-4/15/21). Differences in participant demographics, barriers to care, visit modality (telehealth, in person), and subspeciality of care were studied using unadjusted and adjusted models., Results: There were 3095, 1172 and 3338 unique patient-visits during pre-COVID, early-COVID and late-COVID (overall age 59.5 ± 20.5 years, 57% female, 41.8% White, 25.9% Asian, 16.1% Hispanic). There were disparities in patient age (55.4 ± 21.8 vs. 60.2 ± 19.9 years), race (21.9% vs. 26.9% Asian), ethnicity (18.3% Hispanic vs. 15.2% Hispanic), and insurance (35.9% vs. 45.1% Medicare) as well as changes in modality (14.2% vs. 0% telehealth) and subspecialty (61.6% vs. 70.1% internal exam specialty) in early-COVID vs. pre-COVID (p < .05 for all). In late-COVID, only insurance (42.7% vs. 45.1% Medicare) and modality of care (1.8% vs. 0% telehealth) persisted as differences compared to pre-COVID., Conclusions: There were disparities in patients receiving outpatient ophthalmology care during early-COVID that returned close to pre-COVID baseline one year later. These results suggest that there has not been a lasting positive or negative disruptive effect of the COVID-19 pandemic on disparities in outpatient ophthalmic care.

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.

Background: Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and is typically diagnosed through visualization of the cysts in the cerebral parenchyma by neuro-imaging. However, neuro-imaging may not detect extraparenchymal neurocysticercosis (EPNCC), which is a rare manifestation of the disease involving the subarachnoid, meningeal, and intraventricular spaces. We report 2 cases of extraparenchymal neurocysticercosis, and discuss the diagnostic challenges and management of this entity., Methods: Two cases were identified through clinical records., Results: Both patients had an insidious onset with slow progression of disease, and presented with papilledema and cerebrospinal fluid (CSF) eosinophilia. One case was diagnosed with spinal cord biopsy. The other was diagnosed with CSF serology and next-generation sequencing-based pathogen analysis. Both patients were treated with ventriculoperitoneal shunt, systemic antiparasitic agents, and immunosuppression., Conclusions: EPNCC is less common than parenchymal NCC. A high level of clinical suspicion is required given its rarity, long incubation period, and slow progression. Diagnosis and treatment can be challenging and requires a multidisciplinary approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Background: The accuracy of International Classification of Diseases (ICD) codes for identifying cases of acute optic neuritis (aON) is not known. A prior study reported 61% accuracy for ICD code plus MRI consistent with aON within 2 months. This study determined accuracy for ICD code plus MRI within 2 months regardless of results., Methods: Retrospective chart review was conducted using a medical record research repository of a tertiary care institution from 1998 to 2019. Subjects with ICD-9/10 codes for ON and an MRI brain and/or orbits within 2 months of earliest (initial) ICD code were included. MRI was classified as positive or negative for aON based on report noting gadolinium-contrast enhancement. Clinical diagnosis at the time of initial code was classified as aON, prior ON, considered ON, alternative diagnosis, or unknown based on review of physician authored clinical notes within 7 days of the initial code. Accuracy of ICD code for aON, acute or prior ON, and acute, prior, or considered ON were calculated for all subjects and stratified based on MRI result., Results: Two hundred fifty-one subjects had MRI results within 2 months of their initial ON ICD code (49 positive MRI [previously reported]; 202 negative MRI). Among those with negative MRI, 32 (16%) had aON, 40 (20%) had prior ON, 19 (9%) considered ON as a diagnosis, 92 (46%) had other confirmed diagnoses, and 19 (9%) had unknown diagnosis at time of code. Considering all subjects, accuracy for ICD code was 25% for acute ON, 41% for acute or prior ON, and 48% for acute, prior, or considered ON. Positive MRI, increased number of ON ICD codes, a code given by an ophthalmologist or neurologist within 2 months, and the presence of a neurology encounter within 2 months were associated with an increased accuracy for clinical aON diagnosis., Conclusions: In the setting of an MRI within 2 months, ICD codes for ON have low accuracy for acute ON and only slightly better accuracy for acute or prior ON. Accuracy is higher for cases with a positive MRI than those with a negative MRI, suggesting positive MRI in conjunction with ICD codes may help more accurately identify cases. Reliance on ICD and Current Procedural Terminology codes alone to identify aON cases may introduce substantial misclassification bias in claims-based research., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Importance: Sex disparities exist in academia. Female attendees consistently ask fewer questions in scientific meetings than male attendees, even when they constitute half of the audience., Objective: To assess the role of sex in participation during virtual grand rounds (GR) at a major academic center., Design, Setting, and Participants: In this prospective cohort study, attendees of the Department of Ophthalmology at the University of California, San Francisco, GR from April 2020 to April 2021 were included. All GR were held via a synchronous live video communication platform. During each GR session, a predesignated attendee collected the sex of all attendees, sex of the GR speaker, and sex of each individual who asked a question to the GR speaker in order of inquiry. The GR speakers and audience were unaware of the study. Data were analyzed from June 2021 to April 2023., Main Outcome and Measures: The main analysis assessed the association between being female and asking one of the first 3 questions., Results: A total of 31 virtual ophthalmology GR sessions were observed. The sex of the GR speaker was female in 13 of 31 sessions (42%). The mean (SD) percentage of audience sex at each of the GR sessions was 47% (0.05) female, 45% (0.06) male, and 8% (0.03) unknown. Male attendees were more likely to ask one of the first 3 questions compared with female attendees (prevalence ratio, 3.1; 95% CI, 2.1-4.5; P < .001)., Conclusions and Relevance: Male attendees were more likely to ask questions during virtual ophthalmology GR compared with female attendees at an academic medical center. Strategies to encourage equal participation of sex in academic discourse should be encouraged.

Purpose: To evaluate the effectiveness of plasma exchange (PLEX) for optic neuritis (ON)., Methods: We conducted an international multicenter retrospective study evaluating the outcomes of ON following PLEX. Outcomes were compared to raw data from the Optic Neuritis Treatment Trial (ONTT) using a matched subset., Results: A total of 395 ON attack treated with PLEX from 317 patients were evaluated. The median age was 37 years (range 9-75), and 71% were female. Causes of ON included multiple sclerosis (108), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) (92), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (75), seronegative-NMOSD (34), idiopathic (83), and other (3). Median time from onset of vision loss to PLEX was 2.6 weeks (interquartile range [IQR], 1.4-4.0). Median visual acuity (VA) at the time of PLEX was count fingers (IQR, 20/200-hand motion), and median final VA was 20/25 (IQR, 20/20-20/60) with no differences among etiologies except MOGAD-ON, which had better outcomes. In 81 (20.5%) ON attacks, the final VA was 20/200 or worse. Patients with poor outcomes were older (P = .002), had worse VA at the time of PLEX (P < .001), and longer delay to PLEX (P < .001). In comparison with the ONTT subset with severe corticosteroid-unresponsive ON, a final VA of worse than 20/40 occurred in 6 of 50 (12%) PLEX-treated ON vs 7 of 19 (37%) from the ONTT treated with intravenous methylprednisolone without PLEX (P = .04)., Conclusion: Most ON attacks improved with PLEX, and outcomes were better than attacks with similar severity in the ONTT. The presence of severe vision loss at nadir, older age, and longer delay to PLEX predicted a worse outcome whereas MOGAD-ON had a more favorable prognosis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The purpose of this research was to investigate the characteristics, clinical manifestations, incidence, and risk factors in ethambutol-induced optic neuropathy (EON) in the Thai population., Methods: Patients treated with ethambutol for tuberculosis (TB) were retrospectively identified in the medical record of a tertiary hospital in Thailand from January 2012 to August 2019. Development of EON was determined through review of ophthalmology records. Comparison was made between patients with EON and those without EON to identify possible risk factors. Ophthalmic outcomes were characterized., Results: Among 4,141 patients who received ethambutol for TB treatment, 1,062 had an ophthalmology encounter, and 20 (0.5% overall, 1.88% with ophthalmology encounters) developed EON. In unadjusted analysis, compared to patients without EON, those with EON had a similar daily dose, but longer duration of ethambutol treatment (P=0.02). They were older (mean 43.74 vs. 58.60 years, P=0.001), more likely to have hypertension (P=0.02) and smoke (p=0.01). There were no differences in gender, body mass index, diabetes, dyslipidemia, HIV infection or glomerular filtration rate. The peripapillary retinal nerve fiber layer, ganglion cell analysis, and vascular density as measured using retinal optical coherence tomography were impacted by EON. In adjusted logistic regression analysis, age greater than 60 (OR = 8.71, p = 0.01) and smoking (OR = 7.06, p = 0.01) were independent risk factors for EON., Conclusion: In patients treated with ethambutol, the incidence proportion of EON was 0.5% among those with ethambutol administered and 1.88% among those with ethambutol and an eye visit. Potential EON risk factors were age, hypertension, smoking, and duration of ethambutol medication. Smoking has not been associated with EON in prior studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chaitanuwong, Srithawatpong, Ruamviboonsuk, Apinyawasisuk, Watcharapanjamart and Moss.)

Background: Telehealth was rapidly adopted early in the COVID-19 pandemic as a way to provide medical care while reducing risk of SARS-CoV2 transmission. Since then, telehealth utilization has evolved differentially according to subspecialty. This study assessed changes in neuro-ophthalmology during the first year of the COVID-19 pandemic., Methods: Telehealth utilization and opinions pre-COVID-19, early pandemic (spring 2020), and 1 year later (spring 2021) were surveyed among practicing neuro-ophthalmologists in and outside the United States using an online platform. Demographics, self-reported utilization, perceived benefits, barriers, and examination suitability were collected over a 2-week period in May 2021., Results: A total of 135 practicing neuro-ophthalmologists (81.5% United States, 47.4% females, median age 45-54 years) completed the survey. The proportion of participants using video visits remained elevated during COVID + 1 year (50.8%) compared with pre-COVID (6%, P < 0.0005, McNemar), although decreased compared with early COVID (67%, P < 0.0005). Video visits were the most commonly used methodology. The proportion of participants using remote testing (42.2% vs 46.2%), virtual second opinions (14.5% vs 11.9%, P = 0.45), and eConsults (13.5% vs 16.2%, P = 0.38) remained similar between early and COVID + 1 year ( P = 0.25). The majority selected increased access to care, better continuity of care, and enhanced patient appointment efficiency as benefits, whereas reimbursement, liability, disruption of in-person clinic flow, limitations of video examinations, and patient technology use were barriers. Many participants deemed many neuro-ophthalmic examination elements unsuitable when collected during a live video session, although participants believed some examination components could be evaluated adequately through a review of ancillary testing or outside records., Conclusions: One year into the COVID-19 pandemic, neuro-ophthalmologists maintained telemedicine utilization at rates higher than prepandemic levels. Tele-neuro-ophthalmology remains a valuable tool in augmenting patient care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Background: Episodic high-altitude exposure leads to optic disc edema and retinopathy. It is uncertain whether high-altitude exposure is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION)., Methods: We performed a single-center, retrospective, cross-sectional case study of 5 patients with high-altitude-associated NAION (HA-NAION) from April 2014 to April 2019. Main study parameters included known vascular risk factors for NAION, evolution of visual acuity, visual field, optic disc, and macula measurements., Results: We studied 5 eyes of 5 patients with HA-NAION that occurred at 7,000-9,000 ft above sea level, 28 patients with classic NAION that developed at sea level (normal altitude NAION or NA-NAION), and 40 controls. All 5 patients with HA-NAION had clinically confirmed NAION by a neuro-ophthalmologist within 3-21 days of onset and comprehensive follow-up evaluations (average follow-up of 23 months). Other than high-altitude exposure, 4 of 5 patients had undiagnosed obstructive sleep apnea (OSA, apnea-hypopnea index 5.4-22.2) and 1 had systemic vascular risk factors. All patients had disc-at-risk in the contralateral eye. The best-corrected distance visual acuity was 20/20 to 20/70 (median logMAR 0) at presentation and 20/70 to counting finger (median logMAR 0) at ≥6 months. Automated static perimetry revealed average mean deviation of -18.6 dB at presentation and -22.1 dB at ≥6 months. The average retinal nerve fiber layer was 244 µm (80-348 µm) at onset and 59 µm (55-80 µm) at ≥6 months. The average ganglion cell complex thickness was 50 µm (43-54 µm) at onset and 52 µm (50-55 µm) at ≥6 months. The patients with OSA were started on home continuous positive airway pressure treatment. Visual outcomes were similar in patients with HA-NAION and NA-NAION. - After addressing all NAION risk factors, no new events occurred in the HA-NAION group within 2-8 years with or without repeat high-altitude exposure., Conclusions: NAION can occur under high-altitude conditions. HA-NAION is associated with relatively younger age at onset, disc-at-risk, and OSA. These patients exhibit a relatively progressive course of vision loss after initial onset and severe thinning of optic nerves on optical coherence tomography. Treatment for OSA is recommended, especially with repeated high-altitude exposure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Background: Wyburn-Mason syndrome (WMS) is a neurocutaneous disorder consisting of vascular malformations of the brain, eye, and skin. These include characteristically high-flow intracranial and intraorbital arteriovenous malformations (AVMs) that present commonly with visual deterioration, headache, and hemiplegia. Complete removal of these lesions is challenging. Most patients are followed closely, and intervention occurs only in the setting of worsening symptoms secondary to AVM growth or hemorrhage. Here the authors present the first known case of a patient with WMS and a pituitary macroadenoma., Observations: A 62-year-old man with a 30-year history of WMS with right basal ganglia and orbital AVMs and right eye blindness presented for new-onset left-sided vision loss. A pituitary adenoma was identified compressing the optic chiasm and left optic nerve. Magnetic resonance imaging and digital subtraction angiography studies were obtained for surgical planning, and the patient underwent an endoscopic transnasal transsphenoidal resection, with significant postoperative vision improvement., Lessons: Given the variable presentation and poor characterization of this rare syndrome, patients with WMS presenting with new symptoms must undergo evaluation for growth and hemorrhage of known AVMs, as well as new lesions. Further, in patients undergoing intracranial surgery, extensive preoperative imaging and planning are crucial for safe and successful procedures.

Objective: Previous studies identified risk factors for ischemic optic neuropathy (ION) after cardiac surgery; however, there is no easy-to-use risk calculator for the physician to identify high-risk patients for ION before cardiac surgery. The authors sought to develop and validate a simple-to-use predictive model and calculator to assist with preoperative identification of risk and informed consent for this rare but serious complication., Design: Retrospective case-control study., Setting: Hospital discharge records., Patients: A total of 5,561,177 discharges in the National Inpatient Sample >18 years of age, with procedure codes for coronary artery bypass grafting, heart valve repair/replacement, or left ventricular assist device insertion., Interventions: All patients had undergone cardiac surgery., Measurements and Main Results: Known preoperative risk factors for ION after cardiac surgery were assessed to develop a risk score and prediction model. This model was validated internally using the split-sample method. There were 771 cases of ION among 5,561,177 patients in the National Inpatient Sample. The risk factors for ION used in the model were carotid artery stenosis, cataract, diabetic retinopathy, macular degeneration, glaucoma, male sex, and prior stroke; whereas uncomplicated diabetes decreased risk. With the internal validation, the predictive model had an area under the receiver operating characteristic curve of 0.66. A risk score cutoff ≥3 had 98.4% specificity., Conclusions: This predictive model, based on previously identified preoperative factors, predicted risk of perioperative ION with a fair area under the receiver operating characteristic curve. This predictive model could enable screening to provide a more accurate risk assessment for ION, and consent process for cardiac surgery., Competing Interests: Conflict of Interest Dr. Roth has received compensation for expert witness evaluation and testimony in cases of perioperative visual loss on behalf of patients, hospitals, and health care providers. Drs. Roth and Rubin are Chairs of the American Society of Anesthesiologists (ASA) Task Force on Perioperative Visual Loss. Views expressed in this manuscript are those of the authors only and not of the ASA nor the United States Department of Defense., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The goal of this study was to examine the temporal relationship of eye pain to visual loss and investigate whether timing of steroid treatment affects the rate and extent of visual recovery in optic neuritis (ON) from MOG-IgG associated disease (MOGAD) in a large cohort of MOGAD patients with ON., Methods: This is a multicenter, retrospective cohort study of consecutive MOGAD patients with ON attacks seen from 2017 to 2021 fulfilling the following criteria: (1) clinical history of ON; (2) MOG-IgG seropositivity. ON attacks were evaluated for presence/duration of eye pain, nadir of vision loss, time to intravenous methylprednisolone (IVMP) treatment, time to recovery, and final visual outcomes., Results: There were 107 patients with 140 attacks treated with IVMP and details on timing of treatment and outcomes. Eye pain was present in 125/140 (89%) attacks with pain onset a median of 3 days (range, 0 to 20) prior to vision loss. Among 46 ON attacks treated with IVMP within 2 days of onset of vision loss, median time to recovery was 4 days (range, 0 to 103) compared to 15 days (range, 0 to 365) in 94 ON attacks treated after 2 days (p = 0.004). Those treated within 2 days had less severe VA loss at time of treatment (median LogMAR VA 0.48, range, 0.1 to 3) compared to those treated after 2 days (median LogMAR VA 1.7, range, 0 to 3; p < 0.001), and were more likely to have a VA outcome of 20/40 or better (98% vs 83%, p = 0.01). After adjustment for the initial VA at time of treatment, the differences in final VA were no longer significantly different (p = 0.14). In addition, some patients were documented to recover without steroid treatment., Conclusion: This study suggests that pain precedes vision loss in the majority of ON attacks and early steroids may lead to better outcomes in MOG-IgG ON, but some patients can recover without steroid treatment. Prospective randomized clinical trials are required to confirm these findings., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022. Published by Elsevier B.V.)

The authors reviewed perioperative ocular complications and implications of ocular diseases during nonocular surgeries. Exposure keratopathy, the most common perioperative eye injury, is preventable. Ischemic optic neuropathy, the leading cause of perioperative blindness, has well-defined risk factors. The incidence of ischemic optic neuropathy after spine fusion, but not cardiac surgery, has been decreasing. Central retinal artery occlusion during spine fusion surgery can be prevented by protecting eyes from compression. Perioperative acute angle closure glaucoma is a vision-threatening emergency that can be successfully treated by rapid reduction of elevated intraocular pressure. Differential diagnoses of visual dysfunction in the perioperative period and treatments are detailed. Although glaucoma is increasingly prevalent and often questions arise concerning perioperative anesthetic management, evidence-based recommendations to guide safe anesthesia care in patients with glaucoma are currently lacking. Patients with low vision present challenges to the anesthesia provider that are becoming more common as the population ages., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Background: Ophthalmic outcomes following venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH) are not well characterized., Materials and Methods: A retrospective chart review was conducted on 86 consecutive patients with IIH who underwent venous sinus stenting at Mayo Clinic, Rochester, Minnesota and Stanford Medical Center, Palo Alto, California between May 2015 and October 2021. Patients with raised intracranial pressure from a non-IIH etiology were excluded. Clinical symptoms and neuro-ophthalmological data, including best corrected visual acuity (BCVA), visual field mean deviation, papilledema, and optical coherence tomography (OCT) peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GC-IPL), were analyzed. Baseline measurements before VSS and 3 months or more postoperatively were compared., Results: Eighty-six subjects (82 female) were included in this study, with a median age of 33 (16-68) years and a median body mass index of 36.69 (22.30-62.00) kg/m 2 . 85/86 (98.8%) had attempted prior management with medication, and 12/86 (14%) had prior surgical management with optic nerve sheath fenestration, ventriculoperitoneal shunt, or bariatric surgery. Prior to VSS, 67/86 (77.9%) had papilledema, 85/86 (98.8%) had headaches, and 68/86 (79.1%) had pulsatile tinnitus. For patients with both pre- and post-VSS data available, the average papilledema grade was 1.76 (0-5) (n = 74) and the average OCT pRNFL was 186.34 (52.00-588.00) µm (n = 70), prior to VSS. A median of 4.0 (interquartile range 3.3-5.4) months after VSS, the average papilledema grade improved to 0.39 (0-2), p <0.001, and OCT pRNFL improved to 96.86 (47.00-168.00) µm, p <0.001. 28/86 (32.6%) patients no longer required medication for high intracranial pressure. 14/85 (16.5%) patients reported complete resolution of their headache and 55/71 (77.5%) reported improvement in headache quality. 40/68 (66.7%) reported complete resolution of pulsatile tinnitus. OCT GC-IPL, BCVA, and visual field mean deviation did not significantly change pre- vs post-VSS., Conclusions: Our large consecutive case series corroborates smaller prior studies in demonstrating the overall efficacy of VSS for patients with IIH. We found both ophthalmic improvements, as demonstrated by the significantly reduced papilledema and pRNFL, and overall clinical symptom improvement., Competing Interests: Author HM has the following financial disclosures: NIH P30 026877 and an unrestricted grant from Research to Prevent Blindness. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oyemade, Xu, Brinjikji, Cutsforth-Gregory, Lanzino, Kallmes, Moss, Dodd, Bhatti and Chen.)

Background: Improving patient attendance at medical follow-up visits may have a notable impact on disease and overall health outcomes. Understanding factors contributing to poor attendance is important for identifying at-risk patients and designing interventions to improve clinical outcomes. Our objective was to identify personality and illness perception factors associated with attendance at recommended follow-up visits in a neuro-ophthalmology practice., Methods: New or established patients (≥18 years) with scheduled neuro-ophthalmology (study) or glaucoma (comparison) appointments at a tertiary care academic medical center completed the Brief Illness Perception Questionnaire and Ten-Item Personality Inventory. Physician recommendations made during the visit were recorded (medications, referrals, follow-up, testing, and procedures). A chart review was performed 18 months after enrollment to assess attendance at follow-up appointment and adherence with other physician recommendations. Multiple variable logistic regression models studied associations between follow-up appointment attendance and demographic factors, appointment factors, and survey responses., Results: Among 152 respondents (97% response rate (152 of 157), aged 19-97 years, 58% female, 34% new, 80 neuro-ophthalmology, 72 glaucoma), neuro-ophthalmology subjects were younger, more likely to be White, non-Hispanic, female and new to the practice than subjects with glaucoma. They reported higher emotional impact, identity, and consequences related to their illness (P = 0.001-0.03). Neuro-ophthalmology physician recommendations included more referrals to other services (17.5% vs 1.4%, P = 0.001, chi-square) and more radiology studies (15% vs 0%, P = 0.001, chi-square), but fewer follow-up visits (75% vs 97%, P < 0.0005, chi-square). Among those with recommended follow-up visits, neuro-ophthalmology subjects had lower rates of on-time appointment attendance (55% vs 77%, P = 0.009, chi-square). In a multiple variable model, on-time follow-up attendance was associated with shorter recommended follow-up interval (≤90 days, P < 0.0005), established (vs new) patient status at enrollment visit (P = 0.04), and glaucoma (P = 0.08), but not subject demographics, illness perception, or personality factors., Conclusions: Patient demographics, illness perception, and personality traits were not associated with follow-up appointment attendance and therefore unlikely to be useful for identifying patients at risk of being lost to follow-up. New neuro-ophthalmology patients with a follow-up recommended ≥90 days in advance may benefit from targeted interventions to improve follow-up appointment adherence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Importance: Many patients seen for eye-related issues in the emergency department do not receive recommended follow-up care. Prior evidence supports that scheduling appointments is a barrier to accomplishing the transition to outpatient ophthalmology care., Objective: To evaluate time until appointment scheduling following emergency department discharge with urgent outpatient ophthalmology referral., Design, Setting, and Participants: The A3 problem solving process was implemented by a multidisciplinary team as part of a structured quality improvement program with the goal of reducing the mean time between urgent referral placement in the emergency department and outpatient ophthalmology appointment scheduling. The study was conducted at Stanford Health Care, an academic medical center in Palo Alto, California, affiliated with Stanford University School of Medicine. Using medical center administrative records, all patients discharged from the adult emergency department with an urgent outpatient referral to the Stanford Department of Ophthalmology from August 9 to September 19, 2020 (baseline; n = 43), and from October 26 to November 29, 2020 (after implementation of all interventions; n = 21), were included., Interventions: Interventions developed to target the workflow of the ophthalmology resident, emergency department, ophthalmology clinic, and health system schedulers to address key drivers of the referral-scheduling process included medical record documentation guidelines, identification of responsible parties, preidentified appointment slots, patient education materials, and education of stakeholders, and were implemented by October 25, 2020., Main Outcomes and Measures: Mean time between urgent referral placement (ie, emergency department discharge) and appointment scheduling with outpatient ophthalmology at baseline vs postintervention., Results: At baseline, appointments were scheduled a mean (range) 2.8 (0-7) days after referral placement. In the 5 weeks following implementation of interventions, the mean (range) decreased to 1.3 (0-4) days, a difference of 1.5 days (95% CI, 0.20-2.74; P = .02). This corresponds to 642 (95% CI, 86-1173) days of reduced patient wait time annually. In addition, there was less variability in the number of days between referral and appointment scheduling after intervention compared with baseline., Conclusions and Relevance: The results suggest improvement in efficiency of outpatient ophthalmology appointment scheduling of urgent emergency department referrals could be achieved through application of a quality improvement methodology by a multidisciplinary team representing key stakeholders in the process.

Purpose of Review: The purpose of this review is to summarize current approaches to management of functional vision disorder (FVD)., Recent Findings: Several retrospective studies of FVD in both adults and children have shed light on the range of outcomes and the prevalence of psychosocial stressors among FVD patients. While the first line of treatment for FVD is reassurance and education, recent case reports highlight the use of additional treatment modalities including psychotherapy, hypnosis, and transcranial magnetic stimulation in specific cases. Although the epidemiology and diagnosis of functional vision disorder are well described, there is limited evidence supporting treatment modalities. Nevertheless, the majority of patients improve with conservative management including reassurance, education, and appropriate follow-up. Additional approaches such as mental health care referral can be considered in refractory cases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Misclassification bias is introduced into medical claims-based research because of reliance on diagnostic coding rather than full medical record review. We sought to characterize this bias for idiopathic intracranial hypertension (IIH) and evaluate strategies to reduce it., Methods: A retrospective review of medical records was conducted using a clinical data warehouse containing medical records and administrative data from an academic medical center. Patients with 1 or more instances of International Classification of Diseases (ICD)-9 or -10 codes for IIH (348.2 or G93.2) between 1989 and 2017 and original results of neuroimaging (head CT or MRI), lumbar puncture, and optic nerve examination were included in the study. Diagnosis of IIH was classified as definite, probable, possible, or inaccurate based on review of medical records. The positive predictive value (PPV) for IIH ICD codes was calculated for all subjects, subjects with an IIH code after all testing was completed, subjects with high numbers of IIH ICD codes and codes spanning longer periods, subjects with IIH ICD codes associated with expert encounters (ophthalmology, neurology, or neurosurgery), and subjects with acetazolamide treatment., Results: Of 1,005 patients with ICD codes for IIH, 103 patients had complete testing results and were included in the study. PPV of ICD-9/-10 codes for IIH was 0.63. PPV in restricted samples was 0.82 (code by an ophthalmologist n = 57), 0.70 (acetazolamide treatment n = 87), and 0.72 (code after all testing, n = 78). High numbers of code instances and longer duration between the first and last code instance also increased the PPV., Conclusions: An ICD-9 or -10 code for IIH had a PPV of 63% for probable or definite IIH in patients with necessary diagnostic testing performed at a single institution. Coding accuracy was improved in patients with an IIH ICD code assigned by an ophthalmologist. Use of coding algorithms considering treatment providers, number of codes, and treatment is a potential strategy to reduce misclassification bias in medical claims-based research on IIH. However, these are associated with a reduced sample size., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Background: Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis., Methods: The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan-Meier method., Results: Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2-16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69-0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%-82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%-55.4%]; and low-risk group, 20.8% [95% CI, 14.2%-26.8%]; log-rank P < 0.001)., Conclusions: This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Background: Double Maddox rod (DMR), the gold-standard method for in-office measurement of cyclodeviation, requires an examiner and specialized equipment. The objective of this study was to develop a virtual reality (VR) technique for measurement of cyclodeviation and validate this against the DMR., Methods: A VR-DMR was implemented using a smartphone and commercially available VR viewer. The app displayed a line to each eye and accepted touch inputs from the user to rotate the lines into perceived alignment. VR-DMR cyclodeviation measurements were compared with traditional DMR (T-DMR) cyclodeviation measurements in adults with and without strabismus and children without strabismus., Results: Thirty-one subjects were studied (age 5-88 years, 20 with strabismus). VR-DMR had similar test-retest reliability as T-DMR. VR-DMR was highly correlated with T-DMR (r2 = 0.94, linear regression slope 1.12) with a slight positive bias (linear regression y intercept 1°). VR-DMR was preferred by 54% of subjects with 29% having no preference., Conclusions: A VR method of ocular cyclodeviation measurement using sensory techniques was implemented using commercially available hardware. VR measurements compared favorably with gold-standard DMR measurements, and user feedback was positive. The VR methodology has application for in office and home use by nonexperts for purposes of strabismus monitoring., Competing Interests: The authors report no conflicts of interest, (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Purpose of Review: This article summarizes the impact of pregnancy on neuro-ophthalmic pathways and presents an approach to the evaluation of pregnant women who have neuro-ophthalmic symptoms or signs., Recent Findings: Advances in noninvasive ophthalmic imaging have increased knowledge of the impact of pregnancy on ocular blood flow, which may have relevance for understanding the impact of preeclampsia and eclampsia on the eye., Summary: The framework for approaching neuro-ophthalmic symptoms and signs in pregnant women is similar to the general approach for people who are not pregnant. Visual symptoms are common in preeclampsia and eclampsia. Some diseases that impact the neuro-ophthalmic pathways are more common in pregnant women. Pregnancy should be considered when recommending the workup and treatment for neuro-ophthalmic symptoms and signs., (Copyright © 2022 American Academy of Neurology.)

The diagnostic utility of neuroradiologic signs associated with idiopathic intracranial hypertension (IIH) for the evaluation of patients presenting with papilloedema remains yet to be elucidated. This multicentre retrospective cohort study assessed consecutive patients presenting with suspected papilloedema to Auckland District Health Board (NZ) and Stanford University Medical Centre (US), between 2005 and 2019, undergoing magnetic resonance imaging and venography (MRI/MRV) or computed tomography and venography (CT/CTV) prior to lumbar puncture assessment for diagnostic suspicion of IIH. Data were collected regarding demographic, clinical, radiologic, and lumbar puncture parameters, and the diagnosis of IIH was determined according to the Friedman criteria for primary pseudotumor cerebri syndrome. A total of 204 participants (174 females; mean ± SD age 29.9 ± 12.2 years) were included, and 156 (76.5%) participants fulfilled the diagnostic criteria for IIH. The presence of any IIH-associated radiologic sign on MRI/MRV demonstrated a sensitivity (95% CI) of 74.8% (65.8%-82.0%) and specificity (95% CI) of 94.7% (82.7%-98.5%), while radiologic signs on CT/CTV exhibited a sensitivity (95% CI) of 61.0% (49.9%-71.2%) and specificity (95% CI) of 100.0% (83.2%-100.0%). In summary, the modest sensitivities of radiologic signs of IIH would support the routine use of lumbar puncture assessment following neuroimaging to secure the diagnosis. However, the high specificities might lend limited support for the judicious deferment of lumbar puncture assessment among typical IIH demographic patients who consent to the inherent small risk of missed pathology, which has been proposed by some clinicians., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities., Methods: This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS., Results: Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening., Conclusion: OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials., (Copyright © 2022. Published by Elsevier B.V.)

Background: Optic neuritis (ON) is often the presenting symptom in inflammatory central nervous system demyelinating disorders., Objective: To compare the frequency and pattern of optic chiasm involvement in patients with aquaporin-4-immunoglobulin G (AQP4-IgG)-associated ON to patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated ON., Methods: Retrospective review of all patients evaluated at Mayo Clinic, Stanford University and Ramathibodi Hospital who were found to have: (1) ON, (2) either MOG-IgG or AQP4-IgG by cell-based assay, and (3) magnetic resonance imaging (MRI) at the time of ON. MRI was reviewed for contrast enhancement of the optic chiasm and the pattern of involvement., Results: One hundred and fifty-four patients (74 AQP4-IgG and 80 MOG-IgG) were included. Among patients with AQP4-IgG-ON, 20% had chiasmal involvement, compared with 16% of patients with MOG-IgG-ON ( p = 0.66). In patients with chiasmal involvement, longitudinally extensive optic nerve enhancement (from orbit extending to chiasm) was identified in 54% of MOG-IgG-ON patients, compared with 7% of AQP4-IgG-ON patients ( p = 0.01)., Conclusion: Chiasmal involvement of MOG-IgG-ON and AQP4-IgG-ON occur at more similar frequencies than previously reported. Furthermore, MOG-IgG-ON chiasmal involvement is more likely to be part of a longitudinally extensive optic nerve lesion.

Vision loss with clinical findings that are incompatible with the symptoms and recognized neurological or ophthalmic conditions is a common presentation of patients to neurologists, ophthalmologists, and neuro-ophthalmologists. The accepted terminology to describe such patients has evolved over time, including functional visual disorder (FVD), non-organic vision loss, non-physiologic vision loss, functional vision loss, psychogenic, psychosomatic, and medically unexplained visual loss. Likewise, attitudes and recommended management options have changed over the years in the fields of psychiatry and neurology. FVD is a diagnosis of inclusion, and it is critical that the diagnosis be made and delivered efficiently and effectively to reduce patient and physician duress. We review the current Diagnostic and Statistical Manual (DSM V) terminology and the prior literature on FVD and describe how the approaches to diagnosis and management have changed. We provide recommendations on the appropriate techniques and diagnostic approach for patients with FVD. We also propose a protocol for consistent and standardized discussion with the patient of the diagnosis of FVD. We believe that the adoption of FVD as both a paradigm and nomenclature shift in ophthalmology will improve patient care., (Copyright © 2021. Published by Elsevier Inc.)

Background: Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss., Main Body: Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression., Conclusion: We review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis., (© 2021. The Author(s).)

The photopic negative response of the full-field electroretinogram (ERG) is reduced in optic neuropathies. However, technical requirements for measurement and poor classification performance have limited widespread clinical application. Recent advances in hardware facilitate efficient clinic-based recording of the full-field ERG. Time series classification, a machine learning approach, may improve classification by using the entire ERG waveform as the input. In this study, full-field ERGs were recorded in 217 eyes (109 optic neuropathy and 108 controls) of 155 subjects. User-defined ERG features including photopic negative response were reduced in optic neuropathy eyes ( p < 0.0005, generalized estimating equation models accounting for age). However, classification of optic neuropathy based on user-defined features was only fair with receiver operating characteristic area under the curve ranging between 0.62 and 0.68 and F1 score at the optimal cutoff ranging between 0.30 and 0.33. In comparison, machine learning classifiers using a variety of time series analysis approaches had F1 scores of 0.58-0.76 on a test data set. Time series classifications are promising for improving optic neuropathy diagnosis using ERG waveforms. Larger sample sizes will be important to refine the models., Competing Interests: The RetEVAL device was provided for research use by LKC Technologies Inc. The company had no influence over the design or interpretation of this study. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diao, Kushzad, Patel, Bindiganavale, Wasi, Kochenderfer and Moss.)

Purpose: To develop methods to quantitatively measure retinal vessel tortuosity from fundus images acquired in subjects with papilledema and assess sources of variability in these measurements., Methods: Digital fundus images from 30 eyes of subjects with untreated idiopathic intracranial hypertension and papilledema were analyzed. Retinal vein and artery tortuosities for three to four vessels of each type were measured in a region of interest 1.8 to 2.7 mm from the center of the optic nerve head. Measurements were averaged to generate a venous tortuosity index (VTI) and arterial tortuosity index (ATI) for each eye. One image of each eye was analyzed two times by the same rater. Two images of each eye, differing by focal depth, were analyzed by the same rater. Correlations between VTI and ATI for the same image and different images were calculated., Results: Intrarater Pearson correlations (r) were 0.8 (95% confidence interval [CI], 0.59-0.9) and 0.90 (95% CI, 0.73-0.96) for VTI and ATI, respectively, with one outlier removed. Interimage r values were 0.72 (95% CI, 0.48-0.87) and 0.96 (95% CI, 0.89-0.99) for VTI and ATI, respectively, with one outlier removed. The intraclass correlation coefficients for agreement and consistency were similar, suggesting that the discrepancy between measurements was due to residual random error., Conclusions: The finding of similar intrarater and interimage variability suggests that intrarater variability may be a more dominant source than physiology and image acquisition., Translational Relevance: Standardizing rater procedures and averaging multiple measuring sessions are strategies to reduce variability and improve reliability of detecting retinal vessel tortuosity changes in images of eyes with papilledema.

Background: Misclassification bias is introduced into medical claims-based research because of reliance on diagnostic coding rather than full medical record review. We sought to characterize this bias for idiopathic intracranial hypertension (IIH) and evaluate strategies to reduce it., Methods: A retrospective review of medical records was conducted using a clinical data warehouse containing medical records and administrative data from an academic medical center. Patients with 1 or more instances of International Classification of Diseases (ICD)-9 or -10 codes for IIH (348.2 or G93.2) between 1989 and 2017 and original results of neuroimaging (head CT or MRI), lumbar puncture, and optic nerve examination were included in the study. Diagnosis of IIH was classified as definite, probable, possible, or inaccurate based on review of medical records. The positive predictive value (PPV) for IIH ICD codes was calculated for all subjects, subjects with an IIH code after all testing was completed, subjects with high numbers of IIH ICD codes and codes spanning longer periods, subjects with IIH ICD codes associated with expert encounters (ophthalmology, neurology, or neurosurgery), and subjects with acetazolamide treatment., Results: Of 1,005 patients with ICD codes for IIH, 103 patients had complete testing results and were included in the study. PPV of ICD-9/-10 codes for IIH was 0.63. PPV in restricted samples was 0.82 (code by an ophthalmologist n = 57), 0.70 (acetazolamide treatment n = 87), and 0.72 (code after all testing, n = 78). High numbers of code instances and longer duration between the first and last code instance also increased the PPV., Conclusions: An ICD-9 or -10 code for IIH had a PPV of 63% for probable or definite IIH in patients with necessary diagnostic testing performed at a single institution. Coding accuracy was improved in patients with an IIH ICD code assigned by an ophthalmologist. Use of coding algorithms considering treatment providers, number of codes, and treatment is a potential strategy to reduce misclassification bias in medical claims-based research on IIH. However, these are associated with a reduced sample size., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Idiopathic intracranial hypertension (IIH) is a chronic condition characterized by raised intracranial pressure of undetectable origin, that causes morbidity due to debilitating headaches and vision loss. Continuity of outpatient care is important to monitor for permanent vision loss, manage symptoms and limit emergency care. The purpose of this retrospective study was to identify factors associated with neuro-ophthalmology follow-up appointment completion among patients with IIH at a US academic medical center in order to establish evidence-based interventions to improve adherence patterns. Included are 111 completed or no-show neuro-ophthalmology return outpatient appointments by 23 subjects with IIH. Generalized estimating equation models were used to assess association between appointment completion status and factors previously shown to be associated with appointment adherence. Appointments were more likely to be completed during the summer (p=0.08) and by subjects with headache symptoms (p=0.06), however none of the patient factors reached statistical significance. Completed and no-show appointments did not differ by subject demographic or insurance factors. Further studies are needed to identify risk factors for lack of appointment adherence by patients with IIH, particularly those amenable to intervention, in order to improve continuity of care for IIH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aziz, Shah and Moss.)

Retinal vein changes, which can be observed on clinical exam or ophthalmic imaging, are promising non-invasive biomarkers for elevated intracranial pressure (ICP) as a complement to other markers of high ICP including optic nerve head swelling. Animal and human studies have demonstrated increase in retinal vein pressure associated with elevated ICP mediated by increase in cerebral venous pressure, compression of venous outflow by elevated cerebral spinal fluid pressure in the optic nerve sheath, and compression of venous outflow by optic nerve head swelling. Retinal vein pressure can be estimated using ophthalmodynamometry. Correlates of retinal vein pressure include spontaneous retinal venous pulsations, retinal vein diameter, and retinal vein tortuosity. All of these have potential for clinical use to diagnose and monitor elevated ICP. Challenges include diagnostic prediction based on single clinical measurements and accurate assessment of retinal vein parameters in cases where optic nerve head swelling limits visualization of the retinal veins., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with one of the author, HM., (Copyright © 2021 Moss.)