Hadas Stiebel-Kalish

A 23-year-old male patient presented to the emergency department with several days of exacerbating headaches, bilateral retrobulbar pain, and blurred vision. Ophthalmologic evaluation was consisten...

Severe optic neuritis (ON) is a common clinical manifestation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Given distinct prognoses and often the necessity of early plasma exchange in NMOSD, prompt differentiation is crucial. In this study, we investigated the utility of optical coherence tomography (OCT) in differentiating between first acute NMOSD-ON and MOGAD-associated optic neuritis (MOGAD-ON), as well as specific factors associated with disc edema. In this retrospective multicenter study, 111 adult patients with MOGAD or aquaporin-4 antibody-positive NMOSD who experienced a first ON and underwent OCT within 2 weeks of symptom onset were included from 14 centers across 8 countries. Peripapillary retinal nerve fiber layer (pRNFL) thickness in µm was analyzed, including the average of both eyes in cases of bilateral manifestation. Eighty-three patients with MOGAD (51 women; 124 ON eyes; bilateral ON 48.2%) and 28 with NMOSD (24 women; 36 ON eyes; bilateral ON 21.4%) were enrolled. A significant increase in pRNFL thickness (>2SD), suggestive of disc edema, was observed in 73.4% of MOGAD-ON eyes and 11.1% of NMOSD-ON eyes (p < 0.001). The pRNFL thickness cutoff of 117.5 µm provided 92.9% specificity and 71.1% sensitivity in distinguishing between MOGAD-ON and NMOSD-ON (area under the curve = 0.838). There was no association between pRNFL thickening and MOG-IgG titer (high vs low), body mass index, or the delay between ON onset and OCT. Simultaneous bilateral MOGAD-ON was associated with significantly more pronounced pRNFL thickening. Acute-stage OCT contributes to the rapid and accurate differentiation between MOGAD-ON and NMOSD-ON prior to antibody confirmation, which can be critical for timely therapeutic decisions.

Data on the plasma exchange (PLEX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited. Herein, we evaluate outcomes after PLEX in MOGAD. This international multicenter retrospective cohort study included patients from 18 tertiary care centers in 6 countries. Inclusion criteria included fulfillment of the 2023 International MOGAD panel criteria, receipt of at least 3 sessions of PLEX, and follow-up of ≥3 months after PLEX. Patients with coexisting neuroinflammatory disorders were excluded. We assessed the frequency of complete recovery (CR), clinically significant improvement (CSI), visual acuity (VA), and Expanded Disability Status Scale (EDSS). Logistic regression analyses were performed to identify predictors of CR and CSI. Of 234 patients, 135 (58%) were female. The median (interquartile range [IQR]) age at attack was 34 (IQR 22-49) years, and 42 (17%) were children. In 165 of 243 (68%), the attack treated with PLEX was the first attack. Attack phenotypes included 161 optic neuritis (235 eyes), 77 myelitis, 24 acute disseminated encephalomyelitis, 15 brainstem/cerebellar, 3 cerebral-cortical encephalitis attack, and 1 cerebral polyfocal deficit-36 with >1 core phenotypes. A total of 239 (99%) attacks were also treated with corticosteroids and 32 (13%) with IV immunoglobulins. VA in optic neuritis improved from 20/400 (20/70-hand motion) to 20/20 (20/20-20/30), p < 0.001, and EDSS decreased from a median of 4.0 (3.0-6.5) to 1.0 (0.0-2.5), p < 0.001. Of 229 attacks without subsequent attacks within 3 months, 100 (44%) achieved CR and 213 (93%) CSI. The probability of CR was decreased with advanced age (adjusted odd ratio [95% CI] 0.97 [0.96-0.99] per year), higher EDSS worsening from baseline (0.66 [0.54-0.81] per 0.5 increment) and delayed PLEX (0.98 [0.96-0.99] per day). Advanced age (0.97 [0.96-0.99] per year) and delayed PLEX (0.95 [0.94-0.96] per day) decreased the probability of CSI. We observed favorable outcomes after PLEX in MOGAD attacks. However, advanced age and delayed initiation of PLEX were associated with a reduced probability of improvement. The absence of a control group limits our ability to differentiate PLEX effects from spontaneous recovery, prior corticosteroid response, or long-term immunotherapy. Future prospective studies are needed to assess the impact of PLEX on improvement. This study provides Class IV evidence that PLEX is associated with favorable clinical outcomes in patients with MOGAD.

Large, international, real-world MRI assessments showed high heterogeneity in the data collected from patients with aquaporin-4 immunoglobulin G–seropositive neuromyelitis optica spectrum disorder and frequent cerebral and lower spinal cord abnormalities.

Purpose: The evaluation and management of Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) lacks standardized guidelines. This study aimed to investigate the real-world practices of neuro-ophthalmologists in the evaluation and management of typical NAION cases. Methods: A national survey, conducted between 2019 and 2021, involved all practicing neuro-ophthalmologists. A structured questionnaire assessed their approach to risk factor evaluation and treatment of NAION, with 19 questions about risk factors and six questions concerning treatment and prevention of fellow-eye involvement. Results: Thirty-six out of 37 neuro-ophthalmologists participated. Most physicians referred patients for evaluation of the following risk factors: obstructive sleep apnea (83.3%), diabetes mellitus (83.3%), hypertension (77.7%), dyslipidemia (72.2%), and optic disc drusen (38.8%). However, there was considerable variation in the choice of diagnostic tests recommended. Furthermore, nearly 47% recommended an embolism workup. Regarding treatment, the majority (91%) did not recommend routine treatment for NAION, although in 16.7%, high-dose corticosteroids were occasionally prescribed. Secondary prevention with aspirin (80.6%), smoking cessation advice (86.1%), and advising against erectile dysfunction medications for men (80.6%) were common recommendations. Conclusion: While the risk factors associated with NAION are well-reported, there is a lack of uniformity on which tests should be ordered to evaluate these risk factors. Most neuro-ophthalmologists concur that routine treatment for NAION is not warranted, but not unanimously. Future studies to develop a consensus guideline for post-NAION work-up and management recommendations may assist in the detection and management of preventable risk factors.

Background and ObjectivesMyelin 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. ...

Acute optic neuritis treatment lacks standardized protocols. The value of oral prednisone taper (OPT) following intravenous methylprednisolone (IVMP) on visual outcome parameters in optic neuritis (ON) has never been explored. In the present retrospective study, we investigated whether OPT after IVMP affects the structural and functional visual outcomes of inaugural clinically isolated syndrome (CIS)- or multiple sclerosis (MS)-ON. Adult patients with acute, inaugural, unilateral CIS- or MS-ON, treated with IVMP in Germany and Israel were stratified into patients treated with IVMP alone—versus IVMP and OPT. Inclusion criteria were age ≥18, CIS or MS diagnosis according to McDonald criteria 2017, available visual acuity (VA) at nadir before treatment initiation and at follow-up ≥5 months, as well as a spectral domain optic coherence tomography (OCT) data scan at follow-up. Exclusion criteria included recurrent ON, concomitant ophthalmological comorbidities, optical coherence tomography (OCT) of insufficient quality and ON-related escalation therapy after IVMP. The structural outcome was defined as the average retinal nerve fiber layer (RNFL) difference between the ON-affected and the unaffected eye, while the functional outcome was defined as the final high-contrast best-corrected VA (HC-BCVA) at follow-up compared to nadir. The comparative analysis was performed using linear regression analysis, adjusted for sex, age, and days-to-treatment. Fifty-one patients met the inclusion criteria (25% male). The mean age was 33.9 (±10.23) years. Twenty-six patients (51%) received OPT following IVMP. There was no difference in nadir HC-BCVA between the groups (0.39 No OPT; 0.49 With OPT, P = 0.36). Adjusted linear regression analysis did not indicate an influence of OPT on RNFL thickness or on HC-BCVA (beta coefficient for RNFL difference in percentages: 0.51, 95%-CI: [-4.58, 5.59], beta coefficient for logMAR: 0.11, 95%; CI [-0.12, 0.35] at follow-up. In conclusion, the addition of OPT to IVMP did not affect RNFL thickness or the final VA in a retrospective cohort of 51 patients with inaugural acute CIS- or MS-ON. The results of this exploratory study are currently being re-examined in a large-scale, demographically diverse, prospective study.

Optic neuritis (ON) is a frequent presentation at onset of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The pathophysiology underlying these diseases, especially MOGAD, is still being elucidated. While obesity has been reported to potentially be a risk factor for MS, this has not been explored in NMOSD or MOGAD. We aimed to investigate a possible association between obesity (body mass index [BMI] > 30 kg/m²) in patients with MOGAD, aquaporin 4-IgG positive NMOSD (AQP4-IgG+ NMOSD) or MS. In this multicenter non-interventional retrospective study, data was collected from patients with a first ever demyelinating attack of ON subsequently diagnosed with MOGAD (n = 44), AQP4-IgG+ NMOSD (n = 49) or MS (n = 90) between 2005 and 2020. The following data was collected: age, sex, ethnicity, BMI (documented before corticosteroid treatment), and the ON etiology after diagnostic work-up. A mixed model analysis was performed to assess the potential of obesity or BMI to predict MOGAD-ON, and to distinguish MOGAD-ON from AQP4-IgG+ NMOSD-ON and MS-ON. Main outcome measures included BMI in patients with acute ON and subsequent diagnosis of MOGAD, AQP4-IgG+ NMOSD or MS. A higher BMI was significantly associated with a diagnosis of MOGAD-ON (p < 0.001); in MOGAD patients the mean BMI was 31.6 kg/m² (standard deviation (SD) 7.2), while the mean BMI was 24.7 kg/m² (SD 5.3) in AQP4-IgG+ NMOSD patients, and 26.9 kg/m² (SD 6.2) in MS patients. Mixed-effects multinomial logistic regression, adjusted for age and sex, with obesity as a binary variable, revealed that obesity was associated with a higher odds ratio (OR) of a subsequent MOGAD diagnosis (OR 5.466, 95% CI [2.039, 14.650], p = 0.001) in contradistinction with AQP4-IgG+ NMOSD. This study suggests an association between obesity and MOGAD. Our findings require further exploration, but could have significant pathophysiologic implications if confirmed in larger prospective studies.

Background: Optic neuritis (ON) is a frequent presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-antibody disease (MOGAD) at onset. The pathophysiology underlying these diseases, especially MOGAD, is still being elucidated. While obesity has been reported to potentially be a risk factor for MS, this has not been explored in NMOSD or MOGAD. We aimed to investigate a possible association between obesity (body mass index [BMI] >30 kg/m²) and patients with MOGAD, NMOSD or MS. Methods: Multicenter non-interventional retrospective data collection from a first ever demyelinating attack of ON in patients subsequently diagnosed with MOGAD, NMOSD or MS between 2005-2020. The following data was collected: age, gender, ethnicity, BMI at disease onset and the etiology of ON after diagnostic work-up. A mixed model analysis was performed to assess the ability of obesity or BMI to predict MOGAD-ON and distinguish MOGAD-ON from NMOSD- and MS-ON. Main outcome measures included BMI in patients with acute ON and subsequent diagnosis of MOGAD, NMOSD or MS. Results: One-hundred and eighty-three patients were included: 44 with MOGAD, 49 with NMOSD, and 90 with MS. A higher BMI was significantly associated with a diagnosis of MOGAD-ON (pConclusion: This study suggests an association between obesity and MOGAD. Our finding requires further exploration, but could have significant pathophysiologic implications if confirmed in larger prospective studies.