Optic Neuritis Research Articles

Evaluation of demographic and neuro-ophthalmologic findings of patients with multiple sclerosis.

The study aims to investigate the demographic and neuroophthalmologic features of patients with multiple sclerosis (MS). This retrospective study investigated 270 eyes of 135 patients with MS. All subjects underwent a full ophthalmological examination. The study investigated 270 eyes of 135 patients with MS. The patients included 102 (74.8%) females and 34 (25.2%) males. The mean age at the time of diagnosis of MS was 29.9 ± 9.6years. The mean follow-up period was 6.7 ± 10.9months. Initial symptoms of MS at presentation included optic neuritis (ON) in 42 patients (15.6%), numbness of hands and feet in 20 patients (7.4%) and diplopia in 11 patients (4.1%). Additional diseases were observed in 29 patients (21.5%) and autoimmune diseases were observed in 11 patients (8.1%). Thirteen patients (9.62%) had relatives with MS; the relatives of five patients were first-degree relatives and the relatives of the remaining eight patients were second-degree relatives. Table 2 summarizes the additional systemic and ocular diseases and family history data. During MS, 72 patients (53.4%) were diagnosed with ON. ON was bilateral in 49 patients (68%) and unilateral in 23 patients (32%). Retrobulbar ON was observed in 77 eyes (81.6%) and papillitis was observed in 18 eyes (18.4%). Disorders of efferent visual pathway function were found in 43 patients (30.4%). Visual impairments are significant in patients with MS. Although ON is the most prevalent symptom of MS, it is important to keep in mind that damage to the efferent visual system can be observed.

Polyautoimmunity and multiple autoimmune syndrome in patients with neuromyelitis optica spectrum disorder

BackgroundThe coexistence of neuromyelitis optica spectrum disorders (NMOSD) with other autoimmune diseases (AID) has been increasingly reported. The prevalence and significance of this association are not fully understood. ObjectivesThis study aimed to compare the clinical and laboratory characteristics in NMOSD patients with and without AID. MethodsRetrospective cross-sectional observational study was conducted involving adults meeting NMOSD criteria followed in a neuroimmunology clinic at a tertiary center. Descriptive analysis of clinical/paraclinical/treatment/outcome data collected from the medical records was compared between NMOSD patients with AID (polyautoimmunity) and those without AID. ResultsFrom a cohort of 46 NMOSD patients, 16 (34.8 %) patients, mostly women around 40 years of age, presented with polyautoimmunity: 10 anti-AQP4 positive, 4 anti-MOG positive, and 2 seronegative. Five different organ -specific AID, and six systemic AID were identified in the polyautoimmunity patients group, in addition to 6 cases of multiple autoimmune syndrome. The AID manifestation preceded NMOSD in 10 (62.5 %) patients, with a median interval of 7 years. The NMOSD with polyautoimmunity and NMOSD without AID groups had similar initial clinical manifestations with optic neuritis and/or myelitis being most frequent. Inflammatory CSF, namely elevated proteins, was more common in the polyautoimmunity group (13.0 % in NMOSD vs. 31.3 % in NMOSD+AID, p = 0.003). After a 10±6 years follow-up period, more patients with polyautoimmunity had a relapsing disease (75.0 % in NMOSD vs. 46.7 % in NMOSD+AID, p = 0.012) but no difference in the functional outcome evaluated by the EDSS score was identified. ConclusionsPolyautoimmunity was common in AQP4 positive NMOSD patients leading to a significantly higher risk of disease recorrence. The presence of polyautoimmunity and multiple autoimmune syndrome in NMOSD patients suggests the existence of common susceptibility factors or pathophysiological mechanisms, emphasizing the importance of a multidisciplinary approach to those patients.

Detecting optic nerve lesions in multiple sclerosis patients with a 1,5 T MRI: Evaluation of a 3D DIR sequence compared to a 2D STIR sequence

ObjectivesOptic neuritis is a common clinical presentation in patients suffering from multiple sclerosis (MS). Even though optic neuritis is not part of the MS diagnostic criteria, the diagnosis and consideration of differential diagnoses are important in clinical routine. For the evaluation of the optic nerves with MRI, T2-weighted images with fat suppression, known as short tau inversion recovery sequences (STIR), are often used. Besides that, double inversion recovery (DIR) sequences are being used increasingly in MS patients, especially to determine cortical lesions. The Aim of this study was to evaluate the 3D-DIR for the detection of lesions in the optic nerves in MS patients. MethodsMR examinations of 45 MS-patients containing both STIR and DIR images were independently assessed by two neuroradiologic experienced radiologists, blinded to clinical data. A third neuroradiologic, an experienced radiologist, evaluated the images together, also considering clinical data. These results were considered ground truth and statistically compared to the results of the single readings. To objectify our findings, ROI measurements of affected and unaffected optic nerve segments were made, and a contrast ratio (CR) was calculated. ResultDIR images are statistically equivalent to STIR images concerning the detection of lesions in the optic nerve (p < 0.001). The sensitivity of DIR images (84.7 %) and STIR images (77 %), as well as the specificity (92.2 % and 91.2 %), are comparable. The interrater reliability was substantial for both sequences (κ = 0,73) as well as separated for the STIR images (κ = 0.744) and the DIR images (κ = 0.707). The objective analysis revealed significantly higher CRs in DIR images (p < 0.001). Conclusion3D DIR images showed similar sensitivity and specificity for detecting optic nerve lesions in comparison to dedicated 2D images of the optic nerve. When 3D DIR images are part of the routine scan protocol for evaluating MS patients, additional 2D imaging of the optic nerve is no longer necessary.

COVID-19 Vaccination and Ocular Adverse Events: A Self-Controlled Case Series Study From the Entire South Korean Population

This study aimed to assess the risk of ocular adverse events, including retinal artery occlusion (RAO), retinal vein occlusion (RVO), noninfectious uveitis (NIU), noninfectious scleritis (NIS), optic neuritis (ON), ischemic optic neuropathy (ION), and ocular motor cranial nerve palsy (OMCNP), following Coronavirus Disease 2019 (COVID-19) vaccination. Population-based self-controlled case series METHODS: This study utilized nationwide claims and vaccination data provided by the Korea National Health Insurance Service and Korea Disease Control and Prevention Agency. From the entire South Korean population of 52 million individuals, patients with incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP between January 2021 and March 2022 were included. The postvaccination risk period was defined as up to 56 days after COVID-19 vaccination. The relative incidence rate ratios (IRRs) for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the risk periods were measured using conditional Poisson regression. The study included 6,590, 70,120, 137,958, 17,921, 15,492, 2,039, 49,089, and 11,312 cases of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP, respectively. The IRRs (95% confidence interval) during the early risk period (0-28 days) were 0.95 (0.88-1.01), 0.96 (0.94-0.98), 0.93 (0.91-0.94), 0.93 (0.89-0.96), 0.96 (0.92-1.01), 1.04 (0.92-1.18), 0.98 (0.95-1.00), and 0.91 (0.86-0.96), respectively. In the late risk period (29-56 days), the IRRs were 0.96 (0.89-1.03), 0.93 (0.91-0.96), 0.96 (0.95-0.98), 1.00 (0.95-1.04), 0.96 (0.91-1.01), 1.00 (0.87-1.15), 1.01 (0.98-1.04), and 0.95 (0.90-1.01), respectively. COVID-19 vaccination did not increase the risk of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP during the postvaccination period.

CHALLENGE IN TREATING OPTIC NEURITIS IN PATIENT WITH CEREBRAL TOXOPLASMOSIS RELATED TO IMMUNOCOMPROMISED CONDITION

Introduction: This study aimed to discuss the prognosis of optic neuritis in a patient with cerebral toxoplasmosis related to an immunocompromised condition. Case Report: A 28-year-old female complained of blurred vision and double vision 2 weeks before admission, accompanied by headache, low extremities weakness, dysphonia, and dysphagia. Visual acuity of both eyes was 6/30 and worsened to 6/60 in a couple of days. Anterior segment examination revealed anisocoria pupil, and RAPD was positive in the left eye. Funduscopic examination showed a blurry margin and hyperemia of the optic nerve head. There was impaired eye movement, indicating oculomotor and abducens nerve palsies. High titer of IgG Antibody Toxoplasma (264) and very low titer of CD4 (&lt;50) with non-reactive HIV rapid test were found in laboratory findings. Multiple ring enhancement was shown in MRI finding. Unfortunately, patient passed away during hospitalization due to respiratory failure. Discussion: Toxoplasmosis-associated optic neuritis is rare and usually becomes potentially serious. Although parasite detection by microscopy and bioassay is considered the gold standard for the diagnosis of toxoplasmosis, clinical diagnosis relies more on serological examination methods. The high proportion of deaths from this disease is mostly caused by late diagnosis of the infection. Conclusion: Optic neuritis that accompanied by systemic disorders needs special attention and comprehensive treatment among multidisciplinary divisions, especially in the immunocompromised condition. Early detection and primary prevention are important to improve prognosis and survival rate.

Examining the relative contribution of slow-burning inflammation and chronic demyelination to axonal damage in chronic multiple sclerosis lesions

Background and ObjectivesSlow-burning inflammation at the edge, and chronic demyelination at the core, of established multiple sclerosis (MS) lesions are potential mediators of disease progression. However, their relative contribution to progressive axonal damage has not been explored. Therefore, in this study, we investigated the comparative contribution of slow-burning inflammation and chronic demyelination to axonal attrition within MS lesions by measuring progressive tissue rarefaction. In addition, we use the visual system as a model to investigate the effect of chronic demyelination on the acceleration of axonal death in a sub-group of patients with unilateral optic neuritis. MethodsPre- and post-gadolinium 3D-T1, 3D FLAIR, diffusion tensor images, Optical Coherence tomography and multifocal visual evoked potentials were acquired from 52 relapsing-remitting MS patients who completed at least 5 years follow-up.Lesion expansion was measured using custom software, and the rate of tissue rarefication inside lesion core was assessed by measuring increase of normalized mean diffusivity (nMD). Axonal loss was also examined in eyes with severe optic nerve demyelination. ResultsAmong the 361 lesions analyzed, 104 were expanding (a minimum of 4 % expansion per year) and 257 were stable. Expanding lesions showed a significantly higher rate of progressive tissue rarefication inside lesion (1.12 % per year) core compared to stable lesions (0.21 % per year, p = 0.01). The magnitude of nMD change was significantly correlated with the rate of lesion expansion (r = 0.4, p < 0.001). Analysis of retinal ganglion cells in eyes with severe optic nerve demyelination (Inter-eye latency delay of >10 ms) revealed a similar rate of axonal loss (0.19 %) to the degree of tissue rarefaction observed in stable lesions (0.21 %). DiscussionThe results of the study suggest that the slow-burning inflammation at the lesion's edge (as measured by lesion expansion), is likely to have a greater impact on tissue damage (as measured by nMD change), when compared to stable chronically demyelinated lesions. The similar modest degree of tissue damage was also observed in chronically demyelinated fibers of the optic nerve.

Blurred Margins: An Account of Optic Neuritis in the USSR

Here, we have a patient’s perspective of optic neuritis⎼which is unique enough in itself to bear further inspection. But because the narrative is by an American paleontologist in Soviet Georgia,

Factors That Influence Clinician Prescribing of Corticosteroids for Acute Idiopathic and Multiple Sclerosis-Associated Optic Neuritis: A Qualitative Study.

Treatment with corticosteroids is common for patients with idiopathic and multiple sclerosis-associated optic neuritis (I/MS-ON). Yet, the Optic Neuritis Treatment Trial and meta-analyses confirm that few patients benefit and that visual benefit is of questionable clinical significance, short-lived, and comes with potential harms. The purpose of this study was to uncover the breadth of factors that underlie clinicians' treatment decisions and determine how these factors may influence corticosteroid use for I/MS-ON. We performed semistructured, one-on-one, qualitative interviews with neurologists, neuro-ophthalmologists, and emergency department clinicians at 15 academic and private practices across the United States. The interview guide used the Theoretical Domain Framework and a vignette to explore numerous factors that might influence decision making for definite I/MS-ON. We analyzed transcripts using inductive thematic analysis to generate themes. A total of 22 clinicians were interviewed before thematic saturation was reached: 8 neuro-ophthalmologists, 8 neurologists, and 6 emergency medicine (EM) clinicians (2 physician assistants, 4 physicians). All neuro-ophthalmologists and nearly all neurologists (7 of 8) were aware of risks/benefits of corticosteroid treatment for I/MS-ON. However, neuro-ophthalmologists varied in their corticosteroid treatment recommendation (n = 3 recommended treatment, n = 2 recommended observation, n = 3 recommended shared decision making), whereas all neurologists recommended corticosteroids, indicating that knowledge of corticosteroid risk/benefit alone does not drive decision making. EM clinicians were not aware of risk/benefits of corticosteroid treatment for I/MS-ON and relied on the treatment recommendations of neurologists. Clinicians recommending corticosteroids held personal beliefs that corticosteroids benefit those with worse vision loss, relieve pain, allow earlier return to work, or have easily mitigated side effects. They also perceived that prescribing steroid was the principal method of "doing something," which fit a key provider role. Clinicians who did not recommend corticosteroids or were neutral perceived the risks as nontrivial, considered discussing treatment trade-offs as "doing something" and incorporated patient preferences. Knowledge of risk/benefits of corticosteroids are necessary but not sufficient for evidence-based I/MS-ON practice. Variation in how clinicians treat patients with acute I/MS-ON is influenced largely by psychosocial factors, such as beliefs about corticosteroid risk/benefit trade-offs and the role of the clinician to provide treatment. Interventions to support evidence-based decision making for I/MS-ON treatment will need to provide risk/benefit information to support clinicians with varying levels of expertise, incorporate patient preference, and normalize the option to observe.

Retrobulbar Optic Neuritis after COVID-19 Infection

Purpose: To report a case of retrobulbar optic neuritis after COVID-19 infection.Case summary: A 20-year-old Korean man, without any previous relevant medical history, presented with sudden blurred vision in the left eye that began 6 days after a COVID-19 infection. At his initial visit, the best-corrected visual acuity in the left eye was counting fingers at 30 cm. The pupil showed a grade 2 relative afferent pupillary defect. The fundus exam was normal in both eyes. In the visual evoked potential (VEP) exam, the P100 amplitude of the left eye was decreased and delayed. Orbit magnetic resonance imaging showed asymmetric enlargement and mild enhancement in the left optic nerve. No other lesions were observed around the optic nerve. Steroid pulse therapy was started after a diagnosis of retrobulbar optic neuritis. After 1 month, the patient’s visual acuity had improved to 1.0 in the left eye. The relative afferent pupillary defect and visual field defect disappeared. On VEP, the P100 amplitude recovered, and the delay disappeared.Conclusions: Retrobulbar optic neuritis is a possible neuro-ophthalmological complication of COVID-19 infection. In such cases, high-dose steroid pulse therapy may be helpful, as in the treatment of other forms of optic neuritis.

Trastuzumab-induced optic neuritis: "blindness" side effect.

Trastuzumab improved the prognosis of patients with human epidermal growth factor receptor 2 (HER2)+ breast cancer (BC). Here, we present a patient who developed acute vision loss due to optic atrophy in both eyes after trastuzumab. A 60-year-old female patient was diagnosed with locally advanced HER2+ BC in January 2021. After four cycles of neoadjuvant anthracycline-based chemotherapy followed by four cycles of docetaxel, trastuzumab, and pertuzumab combined treatment, the patient underwent a right modified radical mastectomy. Three days after the end of the second cycle of adjuvant trastuzumab, she presented with acute vision loss. The patient's visual acuity was 90% in the right eye and 60% in the left eye. The left eye had optic nerve edema and spindle hemorrhages. First, on suspicion of optic neuritis, the patient was given a 1 gram/day pulse steroid for three days. However, optic neuritis was not considered during the follow-up. Metastasis was considered at the exit of the left optic nerve. Trastuzumab was started by making a mutual decision with the patient. Six days after the sixth dose of adjuvant trastuzumab, she presented with almost complete vision loss. The patient was diagnosed with optic neuritis, and a pulse steroid was administered. Trastuzumab was permanently discontinued. However, the patient's visual acuity in both eyes remained at 5-10%. Vision loss due to optic neuritis is a devastating side effect. Understanding that trastuzumab-induced optic neuritis may develop will help clinicians detect side effects early and manage them more effectively.

Differentiating optic neuropathies using laser speckle flowgraphy: Evaluating blood flow patterns in the optic nerve head and peripapillary choroid.

To compare blood flow (BF) impairment patterns in different optic neuropathies using laser speckle flowgraphy (LSFG). This retrospective study enrolled 24 eyes of 24 patients with non-arteritic anterior ischemic optic neuropathy (NAAION), 59 eyes of 59 patients with optic neuritis (ON), 677 eyes of 677 patients with open-angle glaucoma (OAG), and 110 eyes of 110 controls. The patient backgrounds of all groups were compared. Ophthalmologic findings were evaluated, adjusting for age, sex, blood pressure, pulse rate, and underlying systemic diseases with 1:1 optimal propensity score matching. We used LSFG to obtain optic nerve head (ONH) vessel-area mean blur rate (MBR; ONH-MV), ONH tissue-area MBR (ONH-MT), and choroidal MBR. The NAAION and ON groups were compared with the control and OAG groups. Best-corrected visual acuity was worse in the NAAION, ON, and OAG groups than in controls (p < 0.001). Circumpapillary retinal nerve fibre layer thickness was higher in the NAAION and ON groups and lower in the OAG group than in controls (p < 0.001). Compared to controls, the NAAION and OAG groups had significantly lower ONH-MV, ONH-MT, and choroidal MBR (p < 0.05). Additionally, the NAAION group had lower ONH-MV and choroidal MBR than the OAG group (p = 0.003 and p < 0.001, respectively) but no difference in ONH-MT (p = 0.857). The ON group had significantly lower ONH-MV and choroidal MBR compared to the controls (p < 0.001 and p = 0.022, respectively) but no difference in ONH-MT (p = 0.773). Optic neuropathies showed different patterns of ocular BF impairment. Therefore, LSFG can be a useful tool for differentiating optic neuropathies.

Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis

ObjectivesLinezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). MethodsWe conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992–2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). ResultsOf all participants (n = 132), 43.2% were female and the median age 28 y. The median linezolid treatment was 6.5 months (IQR 3.0–12.7) with a median daily dose of 9.6 mg/kg/d. Any ADR was seen in 58.3% (n = 77) of participants, with 35.6% having peripheral neuropathy (n = 47), 27.3% anaemia (n = 36), 22.0% leukopenia (n = 36) while 6.1% (n = 8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1–5.9) and 8.3 months (6.2–10.7) for optic neuritis. A >2.0 mg/L trough concentration (n = 40) was associated with anaemia (P = 0.0038) and thrombocytopenia (P = 0.009) but not with peripheral neuropathy. In multivariable analysis, a dose ≥12 mg/kg/d was associated with time to peripheral neuropathy (HR 2.89, 95% CI 1.08–7.74, P = 0.035), anaemia (HR 6.62, 95% CI 2.22–19.8, P = 0.001) and leukopenia (HR 5.23, 95% CI 1.48–18.5, P = 0.010). ConclusionsLinezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity.

Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study.

Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes. Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method. We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%. The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk. This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Study of seasonality of attacks in MOG antibody-associated disease

BackgroundSeasonal variation in attacks of acute disseminated encephalomyelitis (ADEM11ADEM: acute disseminated encephalomyelitis; BS: brainstem; MOG myelin oligodendrocyte glycoprotein; MOGAD: myelin oligodendrocyte glycoprotein antibody-associated disease; NMO neuromyelitis optica; ON: optic neuritis; TM: transverse myelitis) is reported in some studies. Myelin oligodendrocyte glycoprotein (MOG) antibodies are found in up to 50 % of ADEM cases. Despite this, there has been no adequately powered study of seasonality in MOG antibody-associated disease (MOGAD). We sought to determine whether there was an effect of season on incidence of total attacks and onset attacks of MOGAD. MethodsWe searched the large national Oxford-based NMO Service database to identify attacks of MOGAD occurring between 2010 and 2021. Month of each attack was extracted and Edwards’ test of seasonal variation was applied to determine whether there was a seasonal effect on total attacks and onset attacks. ResultsNeither incidence of total attacks nor incidence of onset attacks varied significantly by month. ConclusionThere is no evidence of seasonal fluctuations in the incidence of MOGAD attacks in the UK.

Clinical Patterns and Factors Contributing to Ophthalmic and Otologic Events Associated With Immune Checkpoint Inhibitors: A Narrative Review.

Immune checkpoint inhibitors, which are a type of cancer immunotherapy, have been associated with the development of adverse events related to an overactive immune system caused by the effect of this type of therapy. It affects a wide range of organs, including the ear and eye. Ophthalmic toxicity related to immune checkpoint inhibitors usually occurs bilaterally. Corneal toxicity (mainly dry eye disease) and uveitis are the most commonly reported patterns of toxicity. Other patterns of involvement include optic neuritis, serous retinal detachment, keratitis, ophthalmoplegia, and ocular myasthenia, but are not limited to them. Potential factors contributing to the development of toxicity are age, previous history of ocular immune disease, type, doses, and duration of treatment, and race. Ototoxicity is also reported in the literature, usually manifesting as bilateral, symmetrical/asymmetrical hearing loss. Ear toxicity presenting as ear fullness, tinnitus, and vertigo has also been mentioned in the literature. Hearing loss is often associated with word/speech recognition. An audiogram usually shows a pattern of sensorineural hearing loss. Otitis media has also been reported to be a potential cause of ear toxicity. Immune checkpoint inhibitor toxicity was present more commonly when used along with other anti-neoplastic agents. Ear toxicity, which presumably results from damage to the melanocytes in the ear, often presents with other melanocytotic manifestations, like uveitis and vitiligo. According to the literature, some agents (ipilimumab, nivolumab, atezolizumab, and pembrolizumab) were more commonly associated with toxic effects on the eye and ear and more when combined with each other.

HLA-DR genotypes in patients with primary Sjögren's syndrome in Taiwan.

Different human leukocyte antigen (HLA) genotypes have been known to be associated with the risk of development of Sjögren's syndrome in different populations, but this association has never been reported in Taiwan. We enrolled 1044 subjects (673 patients, 371 controls) and tested their HLA-DR genotypes. We found an increased risk of Sjögren's syndrome in patients carrying HLA-DR8. DR1 and DR14 were associated with increased risk of eye involvement (uveitis, scleritis or optic neuritis), while DR15 was associated with increased risk of interstitial lung disease. DR8 was associated with increased risk of formation of multiple antibodies: anti-Ro, rheumatoid factor and antinuclear antibodies (ANA) reaching titer 1:80 or above. DR9 was associated with decreased risk of formation of anti-La antibodies and increased risk of formation of antithyroglobulin antibodies. DR10 was associated with risk of formation of anticyclic citrullinated peptide (anti-CCP) antibodies, and DR11 was associated with increased risk of formation of anti-La antibodies. Oral ulcer was found to be negatively associated with anti-Ro antibodies and with anti-ENA antibodies. Skin lesions were associated with ANA antibody titer elevation to 1:80 or above. Malignancies of any kind were associated with the presence of cryoglobulin. Females were more likely to be diagnosed at a younger age than males. There was no statistically significant relationship between HLA-DR genotype and age at disease diagnosis. In patients with Sjögren's syndrome in Taiwan, the presence of HLA-DR8 appeared to be a risk factor. In addition, we found several associations between HLA-DR genotype, clinical presentation, and autoantibody status among them.

Application of the international criteria for optic neuritis in the Acute Optic Neuritis Network.

The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON). We included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present. According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%). According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.

The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs.

Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody-associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss. It is important to distinguish MS ON from other ON subtypes early, to guide appropriate management. Yet, identifying ON and differentiating subtypes can be challenging as MRI and serological antibody test results are not always readily available in the acute setting. The purpose of this study is to develop a deep learning artificial intelligence (AI) algorithm to predict subtype based on fundus photographs, to aid the diagnostic evaluation of patients with suspected ON. This was a retrospective study of patients with ON seen at our institution between 2007 and 2022. Fundus photographs (1,599) were retrospectively collected from a total of 321 patients classified into 2 groups: MS ON (262 patients; 1,114 photographs) and non-MS ON (59 patients; 485 photographs). The dataset was divided into training and holdout test sets with an 80%/20% ratio, using stratified sampling to ensure equal representation of MS ON and non-MS ON patients in both sets. Model hyperparameters were tuned using 5-fold cross-validation on the training dataset. The overall performance and generalizability of the model was subsequently evaluated on the holdout test set. The receiver operating characteristic (ROC) curve for the developed model, evaluated on the holdout test dataset, yielded an area under the ROC curve of 0.83 (95% confidence interval [CI], 0.72-0.92). The model attained an accuracy of 76.2% (95% CI, 68.4-83.1), a sensitivity of 74.2% (95% CI, 55.9-87.4) and a specificity of 76.9% (95% CI, 67.6-85.0) in classifying images as non-MS-related ON. This study provides preliminary evidence supporting a role for AI in differentiating non-MS ON subtypes from MS ON. Future work will aim to increase the size of the dataset and explore the role of combining clinical and paraclinical measures to refine deep learning models over time.

Radiologic Predictors of Visual Outcome in Myelin Oligodendrocyte Glycoprotein-Related Optic Neuritis

This study aimed to determine whether magnetic resonance imaging (MRI) biomarkers are associated with visual prognosis in myelin oligodendrocyte protein (MOG)-associated optic neuritis (ON). Cross-sectional analysis. Patients meeting 2023 international diagnostic criteria for MOG antibody-associated disease who were seen for first episodes of MOG-associated ON at 3 tertiary neuro-ophthalmology practices between January 2017 and July 2023 were enrolled. Patients who received < 3 months of neuro-ophthalmic follow-up and did not demonstrate visual recovery (visual acuity [VA] ≥ 20/20 and visual field mean deviation [VFMD] > -5.0 dB) during this time were excluded. Patients underwent contrast-enhanced, fat-suppressed MRI of the brain and orbits within 1 month of symptom onset. The associations between radiologic biomarkers and poor VA outcome (<20/40), incomplete VA recovery (< 20/20), and poor VFMD outcome (VFMD < -5.0 dB) were assessed using multivariable logistic regression adjusting for time from symptom onset to treatment and nadir VA or VFMD. Radiologic biomarkers included length of optic nerve enhancement (> 25% vs. < 25%; > 50%vs.<50%; and >75%vs.< 75%); degree of orbital, canalicular, and intracranial or chiasmal optic nerve enhancement (mild vs. moderate to severe compared with the lacrimal gland); and absence versus presence of optic nerve sheath enhancement on baseline T1-weighted MRI. A total of 129 eyes of 92 patients (median age, 37.0 years [interquartile range, 20.8-51.3 years]; 65.2% female) were included. Poor VA outcome was seen in 6.2% of patients, incomplete VA recovery was seen in 19.4% of patients, and poor VFMD outcome was seen in 16.9% of patients. Compared with eyes with moderate to severe enhancement, eyes with mild orbital optic nerve enhancement were more likely to have poor VA outcome (odds ratio [OR], 8.57; 95% confidence interval [CI], 1.85-51.14; P= 0.009), incomplete VA recovery (OR, 7.31, 95% CI, 2.42-25.47; P= 0.001), and poor VFMD outcome (adjusting for time to treatment: OR, 6.81; 95% CI, 1.85-28.98; P= 0.005; adjusting for nadir VFMD: OR, 11.65; 95% CI, 1.60-240.09; P= 0.04). Lack of optic nerve sheath enhancement additionally was associated with incomplete VA recovery (OR, 3.86; 95% CI, 1.19-12.85; P= 0.02) compared with the presence of enhancement. These associations remained consistent in subgroup logistic regression analysis of MRIs performed before initiation of treatment but were not seen in pairwise analysis of MRIs performed after treatment. In eyes with first MOG-associated ON episodes, milder enhancement in the orbital optic nerve was associated with poorer VA and visual field recovery. Prospective and mechanistic studies are needed to confirm the prognostic usefulness of MRI in MOG-associated ON. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Neuromyelitis optica spectrum disorder: Exploring the diverse clinical manifestations and the need for further exploration.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by inflammatory assaults on the central nervous system (CNS), particularly on the optic nerves and spinal cord. In recent years, a wider range of clinical manifestations of this complex disease have been observed, emphasizing the importance of gaining a more profound understanding beyond optic neuritis (ON) and transverse myelitis (TM). This study explores the many clinical symptoms of NMOSD, including common and uncommon presentations. Distinctive aspects of ON, TM, and diencephalic/brainstem syndromes are examined, highlighting their unique characteristics in contrast to conditions such as multiple sclerosis. We also discuss extra-CNS involvement, such as unusual signs, including muscle involvement, retinal injury, auditory impairment, and rhinological symptoms. Our study intends to highlight the wide range and complexity of NMOSD presentations, emphasizing the significance of identifying unusual symptoms for precise diagnosis and prompt management. The specific processes that contribute to the varied clinical presentation of NMOSD are not well understood despite existing information. This emphasizes the necessity for more study to clarify the mechanisms that cause different symptoms and discover new treatment targets for this complex autoimmune disorder. It is essential to acknowledge the complex and varied clinical manifestations of NMOSD to enhance diagnosis, treatment, and patient results. By enhancing our comprehension of the fundamental processes and investigating innovative therapeutic approaches, we may aim to enhance the quality of life for persons impacted by this illness.