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The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized. [ABSTRACT FROM AUTHOR]

This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Leber's hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background/objectives: Our aim was to compare factors associated with poor versus good visual outcomes in idiopathic intracranial hypertension (IIH) patients with severe papilledema at initial presentation., Subjects/methods: Retrospective review of consecutive IIH patients (1/1/2013-6/10/2023) with severe papilledema (Frisén grade 4-5 and/or atrophy in at least one eye); Patients were divided into "poor visual outcome" (poor visual acuity and constricted visual field in at least one eye) and "good visual outcome" (good visual acuity and only mild visual field changes in both eyes) at >6 months for medically-treated patients and >3 months follow-up for surgically-treated patients., Results: We included 134 IIH patients with severe papilledema (70 had poor and 64 had good visual outcomes). No significant differences existed for age, gender, race, hypertension, haemoglobin, or cerebrospinal fluid opening pressure. The poor-outcome group had significantly greater BMI (mean 39.2 vs 35.1 kg/m 2 , p = 0.004), and worse initial HVF-MD (-20.04 vs -5.81 dB, p < 0.0001). Poor-outcome patients saw more prior health-care providers (4.7 vs 2.4, p < 0.0001), with delayed neuro-ophthalmology encounters (58.5 vs 15.2 weeks, p = 0.001). 41.4% of poor-outcome patients were initially seen in outside emergency departments (ED) (vs 14.1% of good-outcome patients, p = 0.0005), while only 27.1% were seen by eye-care providers (vs 53.1% of good-outcome patients, p = 0.0027). No poor-outcome patients initially consulted our institution's ED vs 7.8% of good-outcome patients., Conclusions: Although patients with poor visual outcome did not seek medical care later than good outcome patients, they had delayed diagnosis/treatment because of prior outside ED visits and lack of prior eye-care provider evaluations, suggesting that early diagnosis and specialized management of papilledema is essential for patients with symptoms of intracranial hypertension., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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.

Our aim was to assess the visual outcomes of patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A MT-ND4 mutation who had no treatment (natural history) or received idebenone or lenadogene nolparvovec. Efficacy outcomes included clinically relevant recovery (CRR) from nadir and final best-corrected visual acuity (BCVA). For the natural history and idebenone groups, we performed a systematic review of the literature and available clinical/regulatory reports. For the lenadogene nolparvovec group, all data from phase 3 studies were included. The overall effect and its 95 % confidence interval (CI) were estimated using a random effects model. For each meta-analysis, patients had a mean age of approximately 30 years at vision loss and were mostly (≥78 %) men. The CRR from nadir [95 % CI] at eye level was 17 % [7 %; 30 %] (n=316 eyes), 31 % [24 %; 40 %] (n=313) and 59 % [54 %; 64 %] (n=348) in untreated, idebenone-treated and lenadogene nolparvovec-treated patients, respectively. This gradient of efficacy was also observed with CRR at the patient level and final BCVA. There was a gradient of efficacy in all assessed visual outcomes, more marked for CRR than for final BCVA, with lenadogene nolparvovec gene therapy superior to idebenone treatment, and both superior to the natural history of the disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Financial support was provided by GenSight Biologics SA. Newman reports a relationship with GenSight Biologics SA that includes: consulting or advisory. Newman reports a relationship with Chiesi Pharmaceuticals Inc that includes: consulting or advisory. Newman reports a relationship with Wuhan Neurophth Biotechnology Co., Ltd. that includes: consulting or advisory. Newman reports a relationship with Stoke Therapeutics Inc that includes: consulting or advisory. Newman reports a relationship with Neurophoenix that includes: consulting or advisory. Newman reports a relationship with GenSight Biologics SA that includes: funding grants. Biousse reports a relationship with GenSight Biologics SA that includes: consulting or advisory. Biousse reports a relationship with Neurophoenix that includes: consulting or advisory. Yu-Wai-Man reports a relationship with GenSight Biologics SA that includes: consulting or advisory. Yu-Wai-Man reports a relationship with Chiesi Pharmaceuticals Inc that includes: consulting or advisory. Yu-Wai-Man reports a relationship with Wuhan Neurophth Biotechnology Co., Ltd. that includes: consulting or advisory. Yu-Wai-Man reports a relationship with Stoke Therapeutics Inc that includes: consulting or advisory. Carelli reports a relationship with GenSight Biologics SA that includes: consulting or advisory. Carelli reports a relationship with Chiesi Pharmaceuticals Inc that includes: consulting or advisory. Carelli reports a relationship with Stoke Therapeutics Inc that includes: consulting or advisory. Carelli reports a relationship with Pretzel Therapeutics, Inc. that includes: consulting or advisory. Vignal-Clermont reports a relationship with GenSight Biologics SA that includes: consulting or advisory. Vignal-Clermont reports a relationship with Chiesi Pharmaceuticals Inc that includes: consulting or advisory. Vignal-Clermont reports a relationship with Neurophoenix that includes: consulting or advisory. Montestruc reports a relationship with eXYSTAT that includes: board membership. Montestruc reports a relationship with AbbVie Inc that includes: consulting or advisory. Montestruc reports a relationship with Arcagy that includes: consulting or advisory. Montestruc reports a relationship with ARTIC that includes: consulting or advisory. Montestruc reports a relationship with Biocodex SA that includes: consulting or advisory. Montestruc reports a relationship with Bioprojet that includes: consulting or advisory. Montestruc reports a relationship with Carely that includes: consulting or advisory. Montestruc reports a relationship with CEVA Inc that includes: consulting or advisory. Montestruc reports a relationship with Cureety that includes: consulting or advisory. Montestruc reports a relationship with Eurofins that includes: consulting or advisory. Montestruc reports a relationship with GeNeuro SA that includes: consulting or advisory. Montestruc reports a relationship with GenSight Biologics SA that includes: consulting or advisory. Montestruc reports a relationship with IFM that includes: consulting or advisory. Montestruc reports a relationship with ImCheck Therapeutics that includes: consulting or advisory. Montestruc reports a relationship with Mapreg that includes: consulting or advisory. Montestruc reports a relationship with Orphelia Pharma Sas that includes: consulting or advisory. Montestruc reports a relationship with OSE Immunotherapeutics that includes: consulting or advisory. Montestruc reports a relationship with Pfizer Inc that includes: consulting or advisory. Montestruc reports a relationship with PTC that includes: consulting or advisory. Montestruc reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Taiel reports a relationship with GenSight Biologics SA that includes: employment. Sahel reports a relationship with Avista Therapeutics that includes: consulting or advisory. Sahel reports a relationship with Tenpoint that includes: consulting or advisory. Sahel reports a relationship with GenSight Biologics SA that includes: equity or stocks. Sahel reports a relationship with Sparing Vision that includes: equity or stocks. Sahel reports a relationship with Prophesee that includes: equity or stocks. Sahel reports a relationship with Chronolife SAS that includes: equity or stocks. Sahel reports a relationship with Tilak Healthcare that includes: equity or stocks. Sahel reports a relationship with VegaVect Inc. that includes: equity or stocks. Sahel reports a relationship with Avista that includes: equity or stocks. Sahel reports a relationship with Tenpoint that includes: equity or stocks. Sahel reports a relationship with SharpEye that includes: equity or stocks. Sahel reports a relationship with Celanese that includes: equity or stocks. Sahel reports a relationship with Netramind that includes: equity or stocks. Sahel has patent Allotopic expression licensed to ‘not applicable’. Sahel has patent Rod-derived Cone Viability factor licensed to INSERM and CNRS. Sahel is owner/co-owner/founder/co-founder of GenSight Biologics, Sparing Vision, Avista, Tenpoint, Prophesee, Chronolife, Tilak Healthcare, SharpEye, Celanese, Vegavect, Netramind. Sahel participates in scientific advisory board for Gilbert Foundation, Foundation Fighting Blindness, Institute of Ophthalmology Basel and Senses Institute Lausanne. Sahel is an observer at Gensight Biologics, SparingVision, Avista and Vegavect. Sahel is President of Fondation Voir et Entendre (Paris) and StreetLab (Paris). Sahel is a recipient for patent royalties and GenSight Biologics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Prior studies have shown that non-arteritic anterior ischemic optic neuropathy (NAION) is uncommon in persons of Black race compared to those of White race, but the reasons behind this discrepancy remain unknown. Our goal was to analyze the systemic and ocular features of Black NAION patients compared to White patients., Design: Retrospective cross-sectional study METHODS: Self-reported race was collected from all NAION patients seen between 2014-2022 from a single US neuro-ophthalmology service. All Black NAION patients and a randomly selected sample of White NAION patients were included. We collected information on hypertension, hyperlipidemia, diabetes mellitus, hypothyroidism, obesity, ischemic heart disease, atrial fibrillation, pacemaker insertion, chronic kidney disease, dialysis, anemia, obstructive sleep apnea, deep vein thrombosis, stroke, use of phosphodiesterase inhibitors, and smoking status. We reviewed color fundus photographs and optic nerve OCT images to assess cup-to-disc ratio and document the presence of optic disc drusen. Counterfactual random forest was used to estimate associations for each characteristic of interest by race controlling for the other exposures., Results: We included 32 Black NAION patients (mean age 57 ± 11 years, 38% men) and 69 of 432 White patients (mean age 57 ± 15 years, 59% men). Time between NAION onset and neuro-ophthalmic examination was significantly longer in Black patients (1.5 to <3 months: OR 4.07, P = 0.03; 6 to <12 months: OR 6.05, P = 0.007). Chronic kidney disease (OR 7.53, P = 0.003) and hemodialysis (OR 13.69, P = 0.02) were significantly more frequent in Black patients. No significant differences in cup-to-disc ratio were present (0.15 to <0.25: OR 2.83, P = 0.09; 0.25 to <0.35: OR 0.56, P = 0.46; ≥0.35: OR 0.66, P = 0.44)., Conclusion: Referral delay occurs in Black patients with NAION, likely due to its relative rarity and concern for alternate diagnoses. Black NAION patients were substantially more likely to have chronic kidney disease and be on dialysis than White patients. Despite known racial differences in cup-to-disc ratio, we found no difference between Black and White NAION patients, suggesting that the underlying proposed compartment mechanism is the same between races., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Despite evidence that non-mydriatic fundus cameras are beneficial in non-ophthalmic settings, they are only available in a minority of hospitals in the US. The lag from research-based evidence to change in clinical practice highlights the complexities of implementation of new technology and practice. We describe the steps used to implement successfully a non-mydriatic ocular fundus camera combined with optical coherence tomography (OCT) in a general emergency department (ED) using Kotter's 8-Step Change Model. We prospectively collected the number of trained personnel in the ED, the number of imaging studies obtained each week during the first year following implementation, and we documented major achievements each month, as well as outcome measures, barriers to implementation and possible solutions. Between 12 and 42 patients were imaged per week, resulting in a total of 1274 patients imaged demonstrating sustained usage of non-mydriatic fundus camera/OCT in the ED one year after implementation. The implementation process was contingent upon multidisciplinary collaboration, extensive communication, coordinated training of staff, and continuous motivation. The future will likely include the use of artificial intelligence deep learning systems for automated interpretation of ocular imaging as an immediate diagnostic aid for ED or other non-eye care providers., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ocular emergencies are commonly evaluated in general emergency departments (ED) where ophthalmologists are rarely available. Nonmydriatic ocular imaging combining color fundus photographs and optical coherence tomography (NMFP-OCT) can help with rapid remote triage by ophthalmologists. We evaluated the rate at which retinal detachments (RDs) can be diagnosed with NMFP-OCT in the ED. Methods: Quality improvement project with prospective collection of data on RD patients who had NMFP-OCT obtained by ED staff over 1 year. Photographs were interpreted remotely by ophthalmologists and all patients underwent an in-person ophthalmologic examination in the ED to confirm the presence of a RD. Results: A total of 63 eyes (58 patients) had a RD, among which 53 (84.1%) had strong suggestion of RD on ocular imaging (34 [54%] were seen on both color and OCT nerve/macula; 11 [17.5%] were seen on color but missed on OCT; 8 [12.7%] were missed on color but seen on OCT). Ten RDs (15.9%) were missed on both color and OCT because of peripheral location of the RD (4, 40%), vitreous hemorrhage (4, 40%), or poor image quality (2, 20%). A total of 40 out of 58 patients were not seen by an eye care provider prior to reaching our ED and 10 had an inappropriate stroke workup for acute vision loss of presumed vascular origin. Conclusion: NMFP-OCT of the posterior pole obtained by ED staff revealed the RD in 84.1% of eyes, allowing for rapid remote triage of patients with visual symptoms and avoiding unnecessary testing when the diagnosis of RD is confirmed.

Background: Optometrists are often the first providers to evaluate patients with acute vision loss and are often the first to diagnose a central retinal artery occlusion (CRAO). How quickly these patients present to the optometrist, are diagnosed, and referred for evaluation are major factors influencing the possibility of acute therapeutic intervention. Our aim was to survey the U.S. optometric community to determine current optometric practice patterns for management of CRAO., Methods: An anonymous seven-question survey was emailed in 2020 to the 5,101 members of the American Academy of Optometry and the 26,502 members of the American Optometric Association., Results: Of 31,603 optometrists who were sent the survey, 1,926 responded (6.1%). Most respondents (1,392/1,919, 72.5%) worked in an optometry-predominant outpatient clinic and were less than 30 minutes from a certified stroke center (1,481/1,923, 77.0%). Ninety-eight percent (1,884/1,922) of respondents had diagnosed less than 5 CRAOs in the previous year, and 1,000/1,922 (52.0%) had not diagnosed a CRAO in the prior year. Of the optometrists who diagnosed at least one CRAO in the previous year, 661/922 (71.7%) evaluated these patients more than 4 hours after the onset of vision loss. Optometrists who diagnosed a CRAO or branch retinal artery occlusion referred patients to an emergency department (ED) affiliated with a certified stroke center (844/1,917, 44.0%), an outpatient ophthalmology clinic (764/1,917, 39.9%), an ED without a stroke center (250/1,917, 13.0%), an outpatient neurology clinic (20/1,917, 1.0%), or other (39/1,917, 2.0%); most (22/39, 56.4%) who responded "other" would refer to a primary care physician., Conclusions: Optometrists are likely the first providers to evaluate patients with acute vision loss, including from a retinal artery occlusion. However, only 6.1% of optometrists responded to our survey despite 2 reminder emails, likely reflecting the lack of exposure to acute retinal artery occlusions, and a potential lack of interest of optometrists in participating in research. Of the optometrists who reported evaluating a CRAO in the previous year, less than 29% saw the patient within 4 hours of vision loss. In addition, a large portion of optometrists are referring acute CRAO patients to outpatient ophthalmology clinics, delaying appropriate acute management. Therefore, it is imperative that optometrists and ophthalmologists are educated to view acute retinal arterial ischemia as an acute stroke and urgently refer these patients to an ED affiliated with a stroke center. The delay in patient presentation and these referral patterns make future clinical trials for acute CRAO challenging., Competing Interests: None of the authors have any conflicts of interest relevant to this work. N. J. Newman is a consultant for GenSight, Santhera/Chiesi and Neurophoenix. V. Biousse is a consultant for GenSight and Neurophoenix., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Competing Interests: The authors report no conflicts of interest.

Background: Visual outcomes of acute central and branch retinal artery occlusions (CRAO/BRAO) are poor and acute treatment options are limited by delayed diagnosis. In the hyper-acute setting, the ocular fundus may appear "normal", making recognition challenging, but is facilitated by retinal optical coherence tomography (OCT), which is seldom available in emergency departments (ED). We evaluated the use of non-mydriatic ocular fundus photographs (NMFP) combined with OCT to facilitate ultra-rapid remote diagnosis and stroke alert for patients with acute vision loss presenting to the ED., Methods: Prospective evaluation of all CRAO/BRAO between 06/06/2023-06/06/2024 who had NMFP-OCT in our general ED affiliated with a stroke center., Results: Over 1 year, 22 patients were diagnosed with CRAO, 4 with BRAO. Five patients presented within 4.5 hours of vision loss onset, 6 within 4.5 to ≤12 hours and 15 within >12 to 24 hours. On average, NMFP-OCT was performed within 141 minutes of presentation to the ED (range 27- 422 minutes). Diagnosis of acute RAO was made remotely with NMFP-OCT within 4.5 hours in 4 patients, 2 of whom received intravenous thrombolysis. Of the 9 patients with NMFP-OCT within 12 hours of symptom onset, 5 patients had subtle retinal whitening on color fundus photograph, but all had OCT inner retinal hyper-reflectivity/edema., Conclusion: Implementation of NMFP-OCT in a general ED enables rapid remote diagnosis of CRAO/BRAO and facilitates initiation of an eye stroke protocol in acute patients. OCT complements color fundus photography and provides greater diagnostic accuracy in hyperacute cases with near-normal appearing ocular fundi., Competing Interests: Declaration of competing interest 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 © 2024 Elsevier Inc. All rights reserved.)

Background: Optic disc drusen (ODD) represent an important differential diagnosis of papilledema caused by intracranial hypertension, but their distinction may be difficult in clinical practice. The aim of this study was to train, validate, and test a dedicated deep learning system (DLS) for binary classification of ODD vs papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs collected in a large international multiethnic population., Methods: This retrospective study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External testing was performed on an independent data set (221 patients), including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study., Results: The DLS could accurately distinguish between all ODD and papilledema (all severities included): area under the receiver operating characteristic curve (AUC) 0.97 (95% confidence interval [CI], 0.96-0.98), accuracy 90.5% (95% CI, 88.0%-92.9%), sensitivity 86.0% (95% CI, 82.1%-90.1%), and specificity 94.9% (95% CI, 92.3%-97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90-0.96), accuracy 84.2% (95% CI, 80.2%-88.6%), sensitivity 78.4% (95% CI, 72.2%-84.7%), and specificity 91.3% (95% CI, 87.0%-96.4%)., Conclusions: A dedicated DLS can accurately distinguish between ODD and papilledema caused by intracranial hypertension, even when considering buried ODD vs mild-to-moderate papilledema., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Introduction: Recent diagnostic criteria for optic neuritis include T2-hyperintensity of the optic nerve (ON), even without associated contrast enhancement. However, isolated ON-T2-hyperintensity is a nonspecific finding found in any optic neuropathy or severe retinopathy. We applied the 2022 optic neuritis diagnostic criteria to a cohort of patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one eye, to assess the rate of optic neuritis misdiagnosis using these criteria., Methods: Retrospective study of consecutive patients who underwent brain/orbit MRI with/without contrast between 07/01/2019 and 06/30/2022. Patients with ON-T2-hyperintensity in at least one eye were included. The 2022 optic neuritis diagnostic criteria were applied to patients with noninflammatory optic neuropathies who had an ophthalmologic examination available for review., Results: Of 150 patients included, 85/150 had compressive optic neuropathy; 32/150 had glaucoma; 12/150 had papilledema; 8/150 had hereditary (3), radiation-induced (3), nutritional (1), traumatic (1) optic neuropathies (none fulfilled the criteria); 13/150 had ischemic optic neuropathy and 4 fulfilled the criteria as definite optic neuritis due to contrast enhancement of the ON head. Seven additional patients would have satisfied the diagnostic criteria if red flags for alternative diagnoses had been overlooked., Discussion: The application of the 2022 optic neuritis diagnostic criteria in patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one ON resulted in misdiagnosis of optic neuritis in only 4 patients because of ON head enhancement, all with nonarteritic anterior ischemic optic neuropathy. Neuro-ophthalmologic evaluation and exclusion of the ON head as a location in the MRI criteria would have prevented optic neuritis misdiagnosis in our study., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/objectives: To report a series of patients with glaucoma and optic nerve abnormalities on magnetic resonance imaging (MRI) in at least one-eye, and to determine whether these findings correlate with the severity of glaucoma., Patients and Methods: Retrospective study of all patients who underwent a brain/orbits MRI without and with contrast at our institution between 07/1/2019-6/30/2022. Patients with optic nerve T2-hyperintensity and/or MRI optic nerve atrophy in at least one-eye and a diagnosis of isolated glaucoma in at least one-eye were included. Demographic information, glaucoma clinical characteristics, glaucoma severity parameters, and MRI indication were collected., Results: Fifty-six patients (112 eyes) (age 65 years-old [range 26-88]; 70% male) had isolated bilateral glaucoma with at least one-eye MRI optic nerve abnormality. The indication for MRI was atypical/asymmetric glaucoma in 91% of patients. Of the 112 eyes, 23 had optic nerve T2-hyperintensity alone; 33 had both optic nerve T2-hyperintensity and MRI optic nerve atrophy; 34 had MRI optic nerve atrophy alone; and 22 did not have abnormal optic nerve MRI-findings. None had optic nerve enhancement. A statistically significant association between optic nerve T2-hyperintensity or MRI optic nerve atrophy and glaucoma severity parameters was found., Conclusions: Glaucoma is a clinical diagnosis and MRI brain is usually not required, except in atypical or asymmetric cases. Optic nerve T2-hyperintensity and MRI optic nerve atrophy are nonspecific MRI-findings that can be found in severe glaucomatous optic nerves and should not systematically prompt investigations for another cause of optic neuropathy., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: The Fundus photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) studies showed that ED providers poorly recognized funduscopic findings in patients in the ED. We tested a modified version of the Brain and Optic Nerve Study Artificial Intelligence (BONSAI) deep learning system on nonmydriatic fundus photographs from the FOTO-ED studies to determine if the deep learning system could have improved the detection of papilledema had it been available to ED providers as a real-time diagnostic aid., Design: Retrospective secondary analysis of a cohort of patients included in the FOTO-ED studies., Methods: The testing data set included 1608 photographs obtained from 828 patients in the FOTO-ED studies. Photographs were reclassified according to the optic disc classification system used by the deep learning system ("normal optic discs," "papilledema," and "other optic disc abnormalities"). The system's performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 1-vs-rest strategy, with reference to expert neuro-ophthalmologists., Results: The BONSAI deep learning system successfully distinguished normal from abnormal optic discs (AUC 0.92 [95% confidence interval {CI} 0.90-0.93]; sensitivity 75.6% [73.7%-77.5%] and specificity 89.6% [86.3%-92.8%]), and papilledema from normal and others (AUC 0.97 [0.95-0.99]; sensitivity 84.0% [75.0%-92.6%] and specificity 98.9% [98.5%-99.4%]). Six patients with missed papilledema in 1 eye were correctly identified by the deep learning system as having papilledema in the other eye., Conclusions: The BONSAI deep learning system was able to reliably identify papilledema and normal optic discs on nonmydriatic photographs obtained in the FOTO-ED studies. Our deep learning system has excellent potential as a diagnostic aid in EDs and non-ophthalmology clinics equipped with nonmydriatic fundus cameras. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Increasing incidence of idiopathic intracranial hypertension (IIH), overreported radiologic signs of intracranial hypertension, difficult access to outpatient neuro-ophthalmology services, poor insurance coverage, and medicolegal concerns have lowered the threshold for emergency department (ED) visits for "papilledema." Our objective was to examine referral patterns and outcomes of neuro-ophthalmology ED and inpatient consultations for concern for papilledema., Methods: At one university-based quaternary care center, all adults referred for "papilledema" over one year underwent a standardized ED "papilledema protocol." We collected patient demographics, final diagnoses, and referral patterns., Results: Over 1 year, 153 consecutive patients were referred for concern for papilledema. After papilledema protocol, 89 of 153 patients (58%) had bilateral optic disc edema, among whom 89% (79/89) had papilledema (intracranial hypertension). Of the 38 of 153 (25%) consultations for suspected disorder of intracranial pressure without previous fundus examination (Group 1), 74% (28/38) did not have optic disc edema, 21% (8/38) had papilledema, and 5% (2/38) had other causes of bilateral disc edema. Of the 89 of 153 (58%) consultations for presumed papilledema seen on fundus examination (Group 2), 58% (66/89) had confirmed papilledema, 17% (15/89) had pseudopapilledema, and 9% (8/89) had other causes of bilateral optic disc edema. Of the 26 of 153 (17%) patients with known IIH (Group 3), 5 had papilledema and 4 required urgent intervention. The most common diagnosis was IIH (58/79). Compared with IIH, patients with secondary causes of intracranial hypertension were older (P = 0.002), men (P < 0.001), not obese (P < 0.001), and more likely to have neurologic symptoms (P = 0.002)., Conclusion: Inpatient and ED consultations for "papilledema" are increasing. Of the 153 ED and inpatient neuro-ophthalmology consultations seen for "papilledema" over 1 year, one-third of patients with optic disc edema of unknown cause before presentation to our ED had new vision- or life-threatening disease, supporting the need for prompt identification and evaluation of optic disc edema in the ED. In the face of limited access to neuro-ophthalmologists, this study supports the need for emergency department access to expert eye-care evaluation or ocular fundus camera for prompt identification of optic disc edema and standardized evaluation for neurologic emergencies., Competing Interests: V. Biousse is a consultant for GenSight Biologics and Neurophoenix and receives research support from GenSight Biologics. N. J. Newman is a consultant for GenSight Biologics, Chiesi, Stoke, Neurophth, Avidity and Neurophoenix; receives research support from GenSight Biologics and Santhera/Chiesi; is a participant in educational webinars sponsored by WebMD-Global Medscape and First Class. The remaining authors report no conflicts of interest., (Copyright © 2024 North American Neuro-Ophthalmology Society.)

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON., Competing Interests: Declaration of interests P.Y.-W.-M., V.C., N.J.N., B.P., L.C., and T.K. received research support and/or personal compensation from Santhera Pharmaceuticals, Chiesi, and GenSight Biologics. P.Y.-W.-M. is also a consultant for Neurophth and Stoke Therapeutics. N.J.N. is also a consultant for Santhera Pharmaceutical, Chiesi, GenSight Biologics, Stoke Therapeutics, Avidity Biosciences, and Neurophoenix SAS, and has been a speaker and contributing writer for educational activities under the auspices of WebMD and First Class. P.S.S. is a consultant to GenSight Biologics and received research support from GenSight Biologics and Santhera Pharmaceuticals. M.H.L. received personal compensation from Santhera Pharmaceuticals. C.L.M. has acted as a consultant for Chiesi Farmaceutici, Regulatory PharmaNet, and Thenewway srl, and has also received speaker honoraria and/or financial support for meetings from these companies, as well as from First Class srl and Biologix. C.L.M. has also acted as a principal or study investigator for clinical trials sponsored by GenSight Biologics, Santhera Pharmaceuticals, Stoke Therapeutics, and Reneo Pharmaceuticals. C.P. received personal compensation from Novartis and has acted as an investigator in clinical trials for Santhera Pharmaceuticals, GenSight Biologics, and Iveric Bio. X.L. and L.T. are employees of Chiesi Farmaceutici S.p.A., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: MRI abnormalities are common in optic neuropathies, especially on dedicated orbital imaging. In acute optic neuritis, optic nerve T2-hyperintensity associated with optic nerve contrast enhancement is the typical imaging finding. In chronic optic neuropathies, optic nerve T2-hyperintensity and atrophy are regularly seen. Isolated optic nerve T2-hyperintensity is often erroneously presumed to reflect optic neuritis, frequently prompting unnecessary investigations and neuro-ophthalmology consultations. Our goal was to determine the significance of optic nerve/chiasm T2-hyperintensity and/or atrophy on MRI., Methods: Retrospective study of consecutive patients who underwent brain/orbital MRI with/without contrast at our institution between July 1, 2019, and June 6, 2022. Patients with optic nerve/chiasm T2-hyperintensity and/or atrophy were included. Medical records were reviewed to determine the etiology of the T2-hyperintensity and/or atrophy., Results: Four hundred seventy-seven patients (698 eyes) were included [mean age 52 years (SD ±18 years); 57% women]. Of the 364 of 698 eyes with optic nerve/chiasm T2-hyperintensity without atrophy, the causes were compressive (104), inflammatory (103), multifactorial (49), glaucoma (21), normal (19), and other (68); of the 219 of 698 eyes with optic nerve/chiasm T2-hyperintensity and atrophy, the causes were compressive (57), multifactorial (40), inflammatory (38), glaucoma (33), normal (7), and other (44); of the 115 of 698 eyes with optic nerve/chiasm atrophy without T2-hyperintensity, the causes were glaucoma (34), multifactorial (21), inflammatory (13), compressive (11), normal (10), and other (26). Thirty-six eyes with optic nerve/chiasm T2-hyperintensity or atrophy did not have evidence of optic neuropathy or retinopathy on ophthalmologic examination, and 17 eyes had clinical evidence of severe retinopathy without primary optic neuropathy., Conclusions: Optic nerve T2-hyperintensity or atrophy can be found with any cause of optic neuropathy and with severe chronic retinopathy. These MRI findings should not automatically prompt optic neuritis diagnosis, workup, and treatment, and caution is advised regarding their use in the diagnostic criteria for multiple sclerosis. Cases of incidentally found MRI optic nerve T2-hyperintensity and/or atrophy without a known underlying optic neuropathy or severe retinopathy are rare. Such patients should receive an ophthalmologic examination before further investigations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Background: Pediatric papilledema often reflects an underlying severe neurologic disorder and may be difficult to appreciate, especially in young children. Ocular fundus photographs are easy to obtain even in young children and in nonophthalmology settings. The aim of our study was to ascertain whether an improved deep-learning system (DLS), previously validated in adults, can accurately identify papilledema and other optic disk abnormalities in children., Methods: The DLS was tested on mydriatic fundus photographs obtained in a multiethnic pediatric population (<17 years) from three centers (Atlanta-USA; Bucharest-Romania; Singapore). The DLS's multiclass classification accuracy (ie, normal optic disk, papilledema, disks with other abnormality) was calculated, and the DLS's performance to specifically detect papilledema and normal disks was evaluated in a one-vs-rest strategy using the AUC, sensitivity and specificity, with reference to expert neuro-ophthalmologists., Results: External testing was performed on 898 fundus photographs: 447 patients; mean age, 10.33 (231 patients ≤10 years of age; 216, 11-16 years); 558 normal disks, 254 papilledema, 86 other disk abnormalities. Overall multiclass accuracy of the DLS was 89.6% (range, 87.8%-91.6%). The DLS successfully distinguished "normal" from "abnormal" optic disks (AUC 0.99 [0.98-0.99]; sensitivity, 87.3% [84.9%-89.8%]; specificity, 98.5% [97.6%-99.6%]), and "papilledema" from "normal and other" (AUC 0.99 [0.98-1.0]; sensitivity, 98.0% [96.8%-99.4%]; specificity, 94.1% (92.4%-95.9%)]., Conclusions: Our DLS reliably distinguished papilledema from normal optic disks and other disk abnormalities in children, suggesting it could be utilized as a diagnostic aid for the assessment of optic nerve head appearance in the pediatric age group., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To explore the risk factors and fundus imaging features of vitamin A deficiency retinopathy (VADR) in an academic tertiary referral center in Atlanta, GA, United States, and to propose guidance regarding diagnostic workup and management of affected patients., Design: Single-center retrospective case series., Subjects: Nine patients seen between 2015 and 2021 at the Emory Eye Center diagnosed with VADR., Methods: Retrospective chart review., Main Outcome Measures: Baseline serum retinol level, Snellen visual acuity, multimodal fundus imaging findings, and electroretinography findings., Results: Nine patients, 4 (44.4%) female, with a median (range) age of 68 (50-75) years were identified. The most common underlying etiologies for vitamin A deficiency included history of gastrointestinal surgery (55.6%), liver disease (44.4%), and nutritional depletion due to low-quality diet (44.4%). Only 1 (11.1%) patient had a history of bariatric surgery. Four (44.4%) patients were on some form of vitamin A supplementation before the diagnosis of VADR. Median (range) serum retinol level was 0.06 (< 0.06-0.19) mg/L. All patients had macular subretinal hyperreflective deposits resembling subretinal drusenoid deposits, although in some cases, these were scant and sparsely distributed. Six eyes of 3 patients with longstanding deficiency had defects in the external limiting membrane (ELM). Three of these eyes additionally had macular areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA). Full-field electroretinography demonstrated severe rod dysfunction and mild to moderate cone system dysfunction. Many findings of VADR were reversible with vitamin A repletion. However, all eyes with ELM defects or cRORA had persistence or continued growth of these lesions., Conclusion: Vitamin A deficiency retinopathy is uncommon in the developed world. However, given that early intervention can lead to dramatic visual improvement and avoid potentially permanent retinal damage, retina specialists should be familiar with its clinical presentation. The presence of nyctalopia and subretinal hyperreflective deposits in a patient with a history of gastrointestinal surgery, liver disease, and/or poor diet can be suggestive of this diagnosis, even in the presence of ongoing vitamin A supplementation. Vitamin A supplementation can vary in route and dosage and can be tailored to the individual with serial testing of serum retinol., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Published by Elsevier Inc.)

Competing Interests: The authors report no conflicts of interest.