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Edsel B Ing,1 Neil R Miller,2 Angeline Nguyen,2 Wanhua Su,3 Lulu LCD Bursztyn,4 Meredith Poole,5 Vinay Kansal,6 Andrew Toren,7 Dana Albreki,8 Jack G Mouhanna,9 Alla Muladzanov,10 Mikaël Bernier,11 Mark Gans,10 Dongho Lee,12 Colten Wendel,13 Claire Sheldon,13 Marc Shields,14 Lorne Bellan,15 Matthew Lee-Wing,15 Yasaman Mohadjer,16 Navdeep Nijhawan,1 Felix Tyndel,17 Arun NE Sundaram,17 Martin W ten Hove,18 John J Chen,19 Amadeo R Rodriguez,20 Angela Hu,21 Nader Khalidi,21 Royce Ing,22 Samuel WK Wong,23 Nurhan Torun24 1Ophthalmology, University of Toronto, Toronto, ON, Canada; 2Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; 3Statistics, MacEwan University, Edmonton, AB, Canada; 4Ophthalmology, Western University, London, ON, Canada; 5Queens University, Kingston, ON, Canada; 6Ophthalmology, University of Saskatchewan, Saskatoon, SK, Canada; 7Laval University, Quebec, QC, Canada; 8Ophthalmology, University of Ottawa, Ottawa, ON, Canada; 9University of Ottawa, Ottawa, ON, Canada; 10Ophthalmology, McGill University, Montreal, QC, Canada; 11University of Sherbrooke, QC, Canada; 12University of British Columbia, Vancouver, BC, Canada; 13Ophthalmology, University of British Columbia, Vancouver, BC, Canada; 14Ophthalmology, University of Virginia, Fisherville, VA, USA; 15Ophthalmology, University of Manitoba, Winnipeg, MB, Canada; 16Ophthalmology, Eye Institute of West Florida, Tampa, FL, USA; 17Neurology, University of Toronto, Toronto, ON, Canada; 18Ophthalmology, Queens University, Toronto, ON, Canada; 19Ophthalmology & Neurology, Mayo Clinic, Rochester, MN, USA; 20Ophthalmology, McMaster University, Hamilton, ON, Canada; 21Rheumatology, McMaster University, Hamilton, ON, Canada; 22Undergraduate Science, Ryerson University, Toronto, ON, Canada; 23Statistics, University of Waterloo, Waterloo, ON, Canada; 24Ophthalmology, Harvard University, Boston, MA, USA Purpose: To develop and validate neural network (NN) vs logistic regression (LR) diagnostic prediction models in patients with suspected giant cell arteritis (GCA). Design: Multicenter retrospective chart review.Methods: An audit of consecutive patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at 14 international medical centers. The outcome variable was biopsy-proven GCA. The predictor variables were age, gender, headache, clinical temporal artery abnormality, jaw claudication, vision loss, diplopia, erythrocyte sedimentation rate, C-reactive protein, and platelet level. The data were divided into three groups to train, validate, and test the models. The NN model with the lowest false-negative rate was chosen. Internal and external validations were performed.Results: Of 1,833 patients who underwent TABx, there was complete information on 1,201 patients, 300 (25%) of whom had a positive TABx. On multivariable LR age, platelets, jaw claudication, vision loss, log C-reactive protein, log erythrocyte sedimentation rate, headache, and clinical temporal artery abnormality were statistically significant predictors of a positive TABx (P≤0.05). The area under the receiver operating characteristic curve/Hosmer–Lemeshow P for LR was 0.867 (95% CI, 0.794, 0.917)/0.119 vs NN 0.860 (95% CI, 0.786, 0.911)/0.805, with no statistically significant difference of the area under the curves (P=0.316). The misclassification rate/false-negative rate of LR was 20.6%/47.5% vs 18.1%/30.5% for NN. Missing data analysis did not change the results.Conclusion: Statistical models can aid in the triage of patients with suspected GCA. Misclassification remains a concern, but cutoff values for 95% and 99% sensitivities are provided (https://goo.gl/THCnuU). Keywords: giant cell arteritis, temporal artery biopsy, neural network, logistic regression, prediction models, ophthalmology, rheumatology

Sivashakthi Kanagalingam,1–3 Neil R Miller1–31Department of Ophthalmology, 2Department of Neurology, 3Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, MD, USAAbstract: Horner syndrome consists of unilateral ptosis, an ipsilateral miotic but normally reactive pupil, and in some cases, ipsilateral facial anhidrosis, all resulting from damage to the ipsilateral oculosympathetic pathway. Herein, we review the clinical signs and symptoms that can aid in the diagnosis and localization of a Horner syndrome as well as the causes of the condition. We emphasize that pharmacologic testing can confirm its presence and direct further testing and management.Keywords: Horner syndrome, oculosympathoparesis, anisocoria, ptosis, anhidrosis

Importance: Prompt and accurate diagnosis of arteritic anterior ischemic optic neuropathy (AAION) from giant cell arteritis and other systemic vasculitis can contribute to preventing irreversible vision loss from these conditions. Its clinical distinction from nonarteritic anterior ischemic optic neuropathy (NAION) can be challenging, especially when systemic symptoms are lacking or laboratory markers of the disease are not reliable., Objective: To develop, train, and test a deep learning system (DLS) to discriminate AAION from NAION on color fundus images during the acute phase., Design, Setting, and Participants: This was an international study including color fundus images of 961 eyes of 802 patients with confirmed AAION and NAION. Training was performed using images from 21 expert neuro-ophthalmology centers in 16 countries, while external testing was performed in a cohort from 5 expert neuro-ophthalmology centers in the US and Europe. Data for training and external testing were collected from August 2018 to January 2023. A mix of deidentified images of 2 fields of view (optic disc centered and macula centered) were used. For training and internal validation, images were from 16 fundus camera models with fields of 30° to 55°. For external testing, images were from 5 fundus cameras with fields of 30° to 50°. Data were analyzed from January 2023 to January 2024., Main Outcomes and Measures: The performance of the DLS was measured using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy., Results: In the training and validation sets, 374 (54.9%) of patients were female, 301 (44.2%) were male, and 6 (0.9%) were of unknown sex; the median (range) age was 66 (23-96) years. When tested on the external dataset including 121 patients (35 [28.9%] female, 44 [36.4%] male, and 42 [34.7%] of unknown sex; median [range] age, 69 [37-89] years), the DLS achieved an AUC of 0.97 (95% CI, 0.95-0.99), a sensitivity of 91.1% (95% CI, 85.2-96.9), a specificity of 93.4% (95% CI, 91.1-98.2), and an accuracy of 92.6% (95% CI, 90.5-96.6). The accuracy of the 2 experts for classification of the same dataset was 74.3% (95% CI, 66.7-81.9) and 81.6% (95% CI, 74.8-88.4), respectively., Conclusions and Relevance: A DLS showing disease-specific averaged class-activation maps had greater than 90% accuracy at discriminating between acute AAION from NAION on color fundus images, at the eye level, without any clinical or biomarker information. A DLS that identifies AAION could improve clinical decision-making, potentially reducing the risk of misdiagnosis and improving patient outcomes.

Competing Interests: Declaration of interests We declare no competing interests.

Purpose: We describe the baseline ophthalmic and cardiovascular risk factors across countries, race, and sex for the Quark207 treatment trial for acute nonarteritic anterior ischemic optic neuropathy (NAION)., Design: Prospective, randomized controlled clinical trial., Participants: Adults 50 to 80 years of age with acute NAION recruited from 80 sites across 8 countries., Main Outcome Measures: Ophthalmic features of NAION and cardiovascular risk factors., Methods: We evaluated demographics and clinical and ophthalmologic data, including best-corrected visual acuity (BCVA) and average visual field total deviation (TD), in affected eyes and cup-to-disc ratio in fellow eyes at enrollment. We report the prevalence (mean and standard devition, and median and interquartile range [IQR]) of ophthalmic features and cardiovascular risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn's test with Bonferroni correction for continuous variables and chi-square testing with Holm-Bonferroni correction for categorical variables., Results: The study enrolled 500 men and 229 women with a median age of 60 and 61 years (P = 0.027), respectively. Participants were predominantly White (n = 570) and Asian (n = 149). The study eye BCVA was 71 characters (IQR, 53-84 characters; approximately 0.4 logarithm of the minimum angle of resolution), and the TD was -16.5 dB (IQR, -22.2 to -12.6 dB) for stimulus III and -15.7 dB (IQR, -20.8 to -10.9 dB) for stimulus V. The vertical and horizontal cup-to-disc ratio was 0.1 (IQR, 0.1-0.3) for unaffected fellow eyes. The prevalence of cardiovascular risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmologic features, which differed between Asian and White races. Men and women differed with respect to a few clinically meaningful features., Conclusions: The cardiovascular risk factors in the NAION cohort varied among the 7 countries, race, and sex, but were not typically more prevalent than in the general population. Ophthalmic features, typical of NAION, generally were consistent across countries, race, and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice that of women. Having a small cup-to-disc ratio in the fellow eye was the most prevalent risk factor across all demographics. This study suggests that factors, not yet identified, may contribute to the development of NAION., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Establishing a molecular diagnosis of mitochondrial diseases due to pathogenic mitochondrial DNA (mtDNA) variants can be difficult because of varying levels of tissue heteroplasmy, and identifying these variants is important for clinical management. Here, we present clinical and molecular findings in 8 adult patients with classical features of mitochondrial ophthalmologic and/or muscle disease and multiple mtDNA deletions isolated to muscle., Methods: The patients were identified via a retrospective review of patients seen in both a tertiary ophthalmology center and a genetics clinic with a clinical diagnosis of chronic progressive external ophthalmoplegia, optic nerve abnormalities, and/or mitochondrial myopathy. Age at onset of symptoms ranged from 18 to 61 years. Ocular manifestations included bilateral optic neuropathy in one patient, bilateral optic disc cupping without optic neuropathy in 2 patients, ptosis in 4 patients, and ocular motility deficits in 2 patients. Five patients had generalized weakness., Results: Pathogenic variants in mtDNA were not found in the blood or buccal sample from any patient, but 7 of 8 patients had multiple mtDNA deletions identified in muscle tissue. One patient had a single mtDNA deletion identified in the muscle. Heteroplasmy was less than 15% for all of the identified deletions, with the exception of one deletion that had a heteroplasmy of 50%-60%. None of the patients were found to have a nuclear gene variant known to be associated with mitochondrial DNA maintenance., Conclusions: mtDNA deletions were identified in adult patients with ophthalmologic and/or musle abnormalities and may underlie their clinical presentations., Competing Interests: H. Cui, K. Allis, A. Balog, and R. Bai are employees of GeneDx in Gaithersburg, MD. All other authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Traumatic optic neuropathy (TON) is a rare but potentially devastating complication of craniofacial trauma. Approximately half of patients with TON sustain permanent vision loss. In this study, we sought to identify the most common fracture patterns associated with TON. We performed a retrospective review of craniomaxillofacial CT scans of trauma patients who presented to the R Adams Cowley Shock Trauma Center from 2015 to 2017. Included were adult patients who had orbital fractures with or without other facial fractures. Patients diagnosed with TON by a formal ophthalmologic examination were analyzed. Craniofacial fracture patterns were identified. Bivariate analysis and multivariate logistic regression were performed to identify craniofacial fracture patterns most commonly associated with TON. A total of 574 patients with orbital fractures who met inclusion criteria [15 (2.6%)] were diagnosed with TON. The median [interquartile range (IQR)] age was 44 (28-59) years. Patients with optic canal fractures and sphenoid sinus fractures had greater odds of TON compared with patients who did not have these fracture types [adjusted odds ratio (aOR) 95% confidence interval (CI) 31.8 (2.6->100), 8.1 (2.7-24.4), respectively]. Patients who sustain optic canal and sphenoid sinus fractures in the setting of blunt facial trauma are at increased odds of having a TON. Surgeons and other physicians involved in the care of these patients should be aware of this association., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

A 64-year-old man presented with 4 months of diplopia. He had end-stage renal disease requiring a cephalic transposition brachiocephalic fistula that was no longer in use following successful renal transplantation. On presentation, he had bilateral proptosis, extraocular movement restriction, chemosis, tortuous episcleral vessels, and caruncular injection. Non-contrast CT of the orbits demonstrated dilation of both superior ophthalmic veins, and CT angiography showed asymmetric enlargement of both cavernous sinuses and superior ophthalmic veins. A carotid-cavernous fistula was suspected, but cerebral angiography revealed shunting from the old fistula with intracranial drainage and cerebral venous hypertension. Aberrant retrograde drainage resulted from anatomical compression of the left brachiocephalic vein. The fistula was ligated, and at 1-week follow-up, the patient had marked improvement in extraocular movements and orbital congestion with near complete resolution of diplopia. Postoperative CT angiography obtained 2 months later demonstrated decreased size of both superior ophthalmic veins, consistent with improvement of venous hypertension., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: A deep learning framework to differentiate glaucomatous optic disc changes due to glaucomatous optic neuropathy (GON) from non-glaucomatous optic disc changes due to non-glaucomatous optic neuropathies (NGONs)., Design: Cross-sectional study., Method: A deep-learning system was trained, validated, and externally tested to classify optic discs as normal, GON, or NGON, using 2183 digital color fundus photographs. A Single-Center data set of 1822 images (660 images of NGON, 676 images of GON, and 486 images of normal optic discs) was used for training and validation, whereas 361 photographs from 4 different data sets were used for external testing. Our algorithm removed the redundant information from the images using an optic disc segmentation (OD-SEG) network, after which we performed transfer learning with various pre-trained networks. Finally, we calculated sensitivity, specificity, F1-score, and precision to show the performance of the discrimination network in the validation and independent external data set., Results: For classification, the algorithm with the best performance for the Single-Center data set was DenseNet121, with a sensitivity of 95.36%, precision of 95.35%, specificity of 92.19%, and F1 score of 95.40%. For the external validation data, the sensitivity and specificity of our network for differentiating GON from NGON were 85.53% and 89.02%, respectively. The glaucoma specialist who diagnosed those cases in masked fashion had a sensitivity of 71.05% and a specificity of 82.21%., Conclusions: The proposed algorithm for the differentiation of GON from NGON yields results that have a higher sensitivity than those of a glaucoma specialist, and its application for unseen data thus is extremely promising., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

Purpose: This study was designed to determine if point analysis of the Humphrey visual field (HVF) is an effective outcome measure for people with idiopathic intracranial hypertension (IIH) compared with mean deviation (MD)., Methods: Using the IIH Weight Trial data, we performed a pointwise analysis of the numerical retinal sensitivity. We then defined a medically treated cohort as having MDs between -2 dB and -7 dB and calculated the number of points that would have the ability to change by 7 dB., Results: The HVF 24-2 mean ± SD MD in the worse eye was -3.5 ± 1.1 dB (range, -2.0 to -6.4 dB). Total deviation demonstrated a preference for the peripheral and blind spot locations to be affected. Points between 0 dB and -10 dB demonstrated negligible ability to improve, compared with those between -10 dB and -25 dB. For the evaluation of the feasibility for a potential medical intervention trial, only 346 points were available for analysis between -10 dB and -25 dB bilaterally, compared with 4123 points in baseline sensitivities of 0 to -10 dB., Conclusions: Patients with IIH have mildly affected baseline sensitivities in the visual field based on HVF analyzer findings, and the majority of points do not show substantial change over 24 months in the setting of a randomized clinical trial. Most patients with IIH who are eligible for a medical treatment trial generally have the mildest affected baseline sensitivities. In such patients, pointwise analysis offers no advantage over MD in detection of visual field change.

This article describes a restorative solution for implants placed at an insufficient depth and in a patient with limited interarch space, making the esthetics, emergence profile, and retention of a cemented restoration problematic. These challenges were overcome by adhesively bonding a pressed lithium disilicate veneer to a custom cast metal abutment veneered with a thin layer of feldspathic porcelain. The ceramic veneer with the attached core engaged a facially located screw-access channel, which increased retention and resistance form and facilitated seating of the veneer. Adhesive bonding via the application of a thin layer of feldspathic porcelain on the custom dental implant abutment was also used to overcome the lack of resistance form with a veneer preparation., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic intracranial hypertension (IIH), a rare neurological disorder, has limited effective long-term treatments. Bariatric surgery has shown short-term promise as a management strategy, but long-term efficacy has not been evaluated. We investigated IIH-related outcomes 4 to 16 years postsurgery., Materials and Methods: This cross-sectional retrospective cohort study included Intracranial Hypertension Registry (IHR) participants with existing medical records that completed a bariatric surgery questionnaire at least 4 years postsurgery. Two physicians independently evaluated the IIH disease course at bariatric surgery and at the time of the questionnaire using detailed medical records. Determinations of improvements were based on within-participant comparisons between the 2 time points. IIH-related outcomes were then combined with bariatric surgery information and outcomes to assess the relationship between weight loss and alterations in IIH., Results: Among participants that underwent bariatric surgery and met study criteria (n=30) the median body mass index (BMI) at the time of surgery was 45.0 [interquartile range (IQR): 39.8-47.0], dropped to a postsurgical nadir of 27.3 (IQR: 22.8-33.1), and rose to 33.4 (IQR: 29.9-41.7) at the time of the questionnaire. Improvements in the IIH disease course at time of the questionnaire occurred in 37% of participants. However, there was a notable association between durable weight loss and IIH improvement as 90% (9 of 10) of participants that attained and maintained a BMI of 30 or below displayed improvement., Conclusions: Attaining and maintaining a BMI of 30 or below was associated with long-term improvement in the IIH disease course, including improved disease management and amelioration of signs and symptoms of participants of the IHR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve (ON)-related vision loss in humans. Study of this disease has been limited by the lack of available tissue and difficulties in evaluating both treatments and the window of effectiveness after symptom onset. The rodent nonarteritic anterior ischemic optic neuropathy model (rNAION) closely resembles clinical NAION in its pathophysiological changes and physiological responses. The rNAION model enables analysis of the specific responses to sudden ischemic axonopathy and effectiveness of potential treatments. However, there are anatomic and genetic differences between human and rodent ON, and the inducing factors for the disease and the model are different. These variables can result in marked differences in lesion development between the two species, as well as in the possible responses to various treatments. These caveats are discussed in the current article, as well as some of the species-associated differences that may be related to ischemic lesion severity and responses.

Purpose of Review: To appraise the literature on the incidence of an acute anterior optic neuropathy resembling spontaneous nonarteritic anterior ischemic optic neuropathy (NAION) following uncomplicated cataract surgery and to explore the proposed pathogenesis of both immediate and delayed onset post-cataract surgery optic neuropathy (PCSON)., Recent Findings: A number of case reports, case series, and retrospective case-controlled, big data, and population-based studies have identified an apparent association between cataract surgery and the occurrence of an acute anterior optic neuropathy that can either be immediate or delayed in onset. However, a recent study found no link between modern day cataract surgery and an increased risk of an acute anterior optic neuropathy., Summary: Immediate PCSON appears to be related to negative perfusion pressure at the level of the optic disc due to increased intraocular pressure. The pathogenesis of delayed PCSON is unknown but probably multifactorial. Patients who have experienced spontaneous NAION or PCSON in one eye may be at risk of PCSON in the fellow eye., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Understanding biological and environmental factors that influence movement behaviors and population connectivity of highly migratory fishes is essential for cooperative international management and conservation of exploited populations, like bluefin tuna. Pacific bluefin tuna Thunnus orientalis (PBT) spawn in the western Pacific Ocean and then juveniles disperse to foraging grounds across the North Pacific. Several techniques have been used to characterize the distribution and movement of PBT, but few methods can provide complete records across ontogeny from larvae to adult in individual fish. Here, otolith biominerals of large PBT collected from the western, eastern, and south Pacific Ocean, were analyzed for a suite of trace elements across calcified/proteinaceous growth zones to investigate patterns across ontogeny. Three element:Ca ratios, Li:Ca, Mg:Ca, and Mn:Ca displayed enrichment in the otolith core, then decreased to low stable levels after age 1-2 years. Thermal and metabolic physiologies, common diets, or ambient water chemistry likely influenced otolith crystallization, protein content, and elemental incorporation in early life. Although similar patterns were also exhibited for otolith Sr:Ca, Ba:Ca and Zn:Ca in the first year, variability in these elements differed significantly after age-2 and in the otolith edges by capture region, suggesting ocean-specific environmental factors or growth-related physiologies affected otolith mineralization across ontogeny., Competing Interests: The authors have declared that no competing interests exist.

The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l; P < 0.0001, Mann-Whitney U-test). These measurements demonstrate a change and imbalance in the biochemical environment of the optic nerve. Its possible effect is discussed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Idiopathic intracranial hypertension (IIH) has an increasing incidence worldwide over the past decade, with a high economic burden on patients and society. Up to 10% of patients with IIH have progressive visual decline requiring an invasive intervention (including cerebrospinal fluid shunting, cerebral dural sinus stenting, or optic nerve sheath fenestration [ONSF]). IIH patients with visual decline usually undergo evaluation and initial management through the emergency department (ED) and commonly have a long hospital stay due to the lack of a dedicated methodology for evaluation and management, particularly in patients who present with visual loss (i.e., fulminant IIH). An innovative practice approach is needed to improve the means of multidisciplinary communication in care and evaluation of IIH patients. This paper aims to discuss the need for the development and implementation of a multidisciplinary "fast-track" strategy for the evaluation and management of patients with fulminant IIH or those with a suboptimal response to maximum tolerated medical treatment at risk for visual loss. We suggest that such a program could reduce hospital stay and ED visits and therefore reduce healthcare costs and improve patient outcomes by accelerating the management process., Competing Interests: SM has received funding for salary support from The Knights Templar Eye Foundation Inc. Professor of Ophthalmology. 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 Miri, Moghekar, Carey, Gailloud and Miller.)

Competing Interests: The authors report no conflicts of interest.

Background: Cavernous malformations (CMs) of the optic nerve and chiasm are extremely rare, accounting for less than 1% of all intracranial CMs. Acute, subacute, or progressive visual loss from CM may occur with or without hemorrhage. Prompt surgical excision of the CM offers the best hope to improve or stabilize vision. Given its rarity, optic nerve and chiasm CMs may not be readily suspected. We provide 3 cases of optic nerve and chiasm CM, highlighting key neuroimaging features and the importance of expedited intervention., Methods: Case records of the neuro-ophthalmology clinics of the Bascom Palmer Eye Institute and the University of Colorado, and literature review of reported cases of optic CM., Results: A 49-year-old woman reported acute progressive painless vision loss in the right eye. MRI showed a suprasellar mass with heterogeneity in signal involving the right prechiasmatic optic nerve. Surgical excision of the CM 5 days after onset of visual loss improved vision from 20/300 to 20/30. A 29-year-old woman with acute painless blurred vision in the right eye had anterior chiasmal junctional visual field defects corresponding to a heterogeneously minimally enhancing mass with blood products enlarging the optic chiasm and proximal right optic nerve. Surgical excision of the CM 8 weeks after onset of visual loss improved vision from 20/40 to 20/15 with improved visual fields. A 33-year-old woman with a history of familial multiple CMs, diagnosed at age 18, reported new-onset severe headache followed by blurred vision. MRI showed a hemorrhagic lesion of the optic chiasm and right optic tract. She was 20/20 in each eye with a reported left superior homonymous hemianopia. No intervention was recommended. Vision of the right eye worsened to 20/400 2 months later. The patient was followed over 13 years, and the MRI and visual function remained unchanged. Literature review yielded 87 optic CM cases occurring across gender and nearly all ages with visual loss and headache as the most common presenting symptoms. Optic chiasm is the most common site of involvement (79%). Nearly 95% of reported CM cases were treated with surgery with 81% with improved vision and 1% with worsened vision., Conclusion: MRI features are critical to the diagnosis of optic nerve and chiasm CM and may mimic other lesions. A high index of suspicion by the neuro-ophthalmologist and neuroradiologist leads to early recognition and intervention. Given optic CM displaces and does not infiltrate neural tissue, expedited surgical resection by a neurosurgeon after consideration of other diagnostic possibilities improves visual function in most cases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Competing Interests: The authors report no conflicts of interest.

Background: To date, deep learning-based detection of optic disc abnormalities in color fundus photographs has mostly been limited to the field of glaucoma. However, many life-threatening systemic and neurological conditions can manifest as optic disc abnormalities. In this study, we aimed to extend the application of deep learning (DL) in optic disc analyses to detect a spectrum of nonglaucomatous optic neuropathies., Methods: Using transfer learning, we trained a ResNet-152 deep convolutional neural network (DCNN) to distinguish between normal and abnormal optic discs in color fundus photographs (CFPs). Our training data set included 944 deidentified CFPs (abnormal 364; normal 580). Our testing data set included 151 deidentified CFPs (abnormal 71; normal 80). Both the training and testing data sets contained a wide range of optic disc abnormalities, including but not limited to ischemic optic neuropathy, atrophy, compressive optic neuropathy, hereditary optic neuropathy, hypoplasia, papilledema, and toxic optic neuropathy. The standard measures of performance (sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC-ROC)) were used for evaluation., Results: During the 10-fold cross-validation test, our DCNN for distinguishing between normal and abnormal optic discs achieved the following mean performance: AUC-ROC 0.99 (95 CI: 0.98-0.99), sensitivity 94% (95 CI: 91%-97%), and specificity 96% (95 CI: 93%-99%). When evaluated against the external testing data set, our model achieved the following mean performance: AUC-ROC 0.87, sensitivity 90%, and specificity 69%., Conclusion: In summary, we have developed a deep learning algorithm that is capable of detecting a spectrum of optic disc abnormalities in color fundus photographs, with a focus on neuro-ophthalmological etiologies. As the next step, we plan to validate our algorithm prospectively as a focused screening tool in the emergency department, which if successful could be beneficial because current practice pattern and training predict a shortage of neuro-ophthalmologists and ophthalmologists in general in the near future., Competing Interests: D. Myung is a co-inventor of a patent on the Paxos portable camera that was used in the study. The remaining authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Geochemical chronologies were constructed from otoliths of adult Pacific bluefin tuna (PBT) to investigate the timing of age-specific egress of juveniles from coastal nurseries in the East China Sea or Sea of Japan to offshore waters of the Pacific Ocean. Element:Ca chronologies were developed for otolith Li, Mg, Mn, Zn, Sr, and Ba, and our assessment focused on the section of the otolith corresponding to the age-0 to age-1 + interval. Next, we applied a common time-series approach to geochemical profiles to identify divergences presumably linked to inshore-offshore migrations. Conspicuous geochemical shifts were detected during the juvenile interval for Mg:Ca, Mn:Ca, and Sr:Ca that were indicative of coastal-offshore transitions or egress generally occurring for individuals approximately 4-6 mo. old, with later departures (6 mo. or older) linked to overwintering being more limited. Changepoints in otolith Ba:Ca profiles were most common in the early age-1 period (ca. 12-16 mo.) and appear associated with entry into upwelling areas such as the California Current Large Marine Ecosystem following trans-Pacific migrations. Natal origin of PBT was also predicted using the early life portion of geochemical profile in relation to a baseline sample comprised of age-0 PBT from the two primary spawning areas in the East China Sea and Sea of Japan. Mixed-stock analysis indicated that the majority (66%) of adult PBT in our sample originated from the East China Sea, but individuals of Sea of Japan origin were also detected in the Ryukyu Archipelago., (© 2021. The Author(s).)

Nonarteritic anterior ischemic optic neuropathy (NAION) commonly causes sudden optic nerve (ON)-related vision loss. The rodent NAION model (rAION) closely resembles NAION in presentation and physiological responses. We identified early rAION-associated optic nerve head (ONH) inflammatory gene expression responses and the anti-inflammatory prostaglandin PGJ 2 's effects on those responses. We hypothesized that blocking pro-inflammatory prostaglandin (PGE 2 ) production by inhibiting monoacylglycerol lipase or cyclooxygenase activity and co-administering PGJ 2 would potentiate RGC survival following ischemic neuropathy. Deep sequencing was performed on vehicle- and PGJ 2 -treated ONHs 3d post-rAION induction. Results were compared against responses from a retinal ischemia model. Animals were treated with PGJ 2 and MAGL inhibitor KML29, or PGJ 2 + COX inhibitor meloxicam. RGC survival was quantified by stereology. Tissue PG levels were quantified by ELISA. Gene expression was confirmed by qPCR. PGJ 2 treatment nonselectively reduced inflammatory gene expression post-rAION. KML29 did not reduce PGE 2 1d post-induction and KML29 alone increased RGC loss after rAION. Combined treatments did not improve ONH edema and RGC survival better than reported with PGJ 2 alone. KML29's failure to suppress PGE 2 ocular synthesis, despite its purported effects in other CNS tissues may result from alternative PG synthesis pathways. Neither KML29 nor meloxicam treatment significantly improved RGC survival compared with vehicle. While exogenous PGJ 2 has been shown to be neuroprotective, treatments combining PGJ 2 with these PG synthesis inhibitors do not enhance PGJ 2 's neuroprotection.

Background: En face optical coherence tomography (OCT) uses the data acquired during OCT of the optic disc, which typically is used to determine measurements of the peripapillary retinal nerve fiber layer (ppRNFL), to generate a coronal composite fundus image rather than a cross-sectional image. En face OCT has been reported to identify retinal changes related to papilledema in idiopathic intracranial hypertension (IIH) but has not been evaluated for monitoring papilledema. This study aimed to assess the reliability and validity of en face OCT for monitoring papilledema., Methods: Using the Pearson correlation coefficient (R), these measurements were compared with ppRNFL thickness as well as average diameter and estimated area. Four fellowship-trained neuro-ophthalmologists were asked to qualitatively rank en face images by the area of optic disc edema while masked from all other clinical data. Rankings were compared with ppRNFL thickness as a gold standard and with en face OCT characteristics using the Pearson correlation coefficient (R)., Results: Experts were able to correctly identify an increase in average ppRNFL thickness >10 µm with a mean (SD) of 91% (±7%) accuracy. A ranking error among experts corresponded to a mean (standard error) change in the ppRNFL thickness of 6 (±6) µm. The mean Pearson correlation coefficient by the area of disc edema among experts was 0.92 (±0.13)., Conclusions: Multiple objective parameters of en face OCT of optic disc edema have an excellent correlation with ppRNFL thickness. These results suggest that en face OCT is a valid clinical tool for monitoring papilledema in IIH., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: The authors report no conflicts of interest.