Optic Neuritis Research Articles

Retinal Damage and Visual Network Reconfiguration Defines Visual Function Recovery in Optic Neuritis.

Recovery of vision after acute optic neuritis (AON) is critical to improving the quality of life of people with demyelinating diseases. The objective of the study was to prospectively assess the changes in visual acuity, retinal layer thickness, and cortical visual network in patients with AON to identify the predictors of permanent visual disability. We studied a prospective cohort of 88 consecutive patients with AON with 6-month follow-up using high and low-contrast (2.5%) visual acuity, color vision, retinal thickness from optical coherence tomography, latencies and amplitudes of multifocal visual evoked potentials, mean deviation of visual fields, and diffusion-based structural (n = 53) and functional (n = 19) brain MRI to analyze the cortical visual network. The primary outcome was 2.5% low-contrast vision, and data were analyzed with mixed-effects and multivariate regression models. We found that after 6 months, low-contrast vision and quality of vision remained moderately impaired. The thickness of the ganglion cell layer at baseline was a predictor of low-contrast vision 6 months later (ß = 0.49 [CI 0.11-0.88], p = 0.012). The structural cortical visual network at baseline predicted low-contrast vision, the best predictors being the betweenness of the right parahippocampal cortex (ß = -036 [CI -0.66 to 0.06], p = 0.021), the node strength of the right V3 (ß = 1.72 [CI 0.29-3.15], p = 0.02), and the clustering coefficient of the left intraparietal sulcus (ß = 57.8 [CI 12.3-103.4], p = 0.015). The functional cortical visual network at baseline also predicted low-contrast vision, the best predictors being the betweenness of the left ventral occipital cortex (ß = 8.6 [CI: 4.03-13.3], p = 0.009), the node strength of the right intraparietal sulcus (ß = -2.79 [CI: -5.1-0.4], p = 0.03), and the clustering coefficient of the left superior parietal lobule (ß = 501.5 [CI 50.8-952.2], p = 0.03). The assessment of the visual pathway at baseline predicts permanent vision disability after AON, indicating that damage is produced early after disease onset and that it can be used for defining vision impairment and guiding therapy.

Recent advances in neuro-ophthalmology.

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.

Optic Neuritis and its Prevalence in Immunocompromised Patients: A Review Article

Optic neuritis is an inflammation that affects the optic nerve, causing vision loss, eye pain, and changes in color perception. The condition can be associated with autoimmune diseases such as multiple sclerosis (MS) or infections, especially in immunocompromised individuals such as HIV/AIDS patients or those undergoing chemotherapy. In these individuals, optic neuritis usually results from opportunistic infections like toxoplasmosis and syphilis, complicating diagnosis and treatment. In immunocompetent patients, optic neuritis may indicate autoimmune diseases like MS or neuromyelitis optica (NMO), with better prognoses when treated early with corticosteroids. However, in immunocompromised individuals, the prognosis tends to be worse due to underlying infections and a limited response to immunosuppressive treatment. The management of optic neuritis involves anti-inflammatory therapies and, in cases of infections, specific antimicrobials. Continuous clinical and visual follow-up is also crucial. Studies suggest that clinical outcomes vary depending on the etiology and the patient's immune status, highlighting the need for personalized therapeutic strategies. Early diagnosis is critical to improving vision and quality of life for patients.

Overview of emerging therapies for demyelinating diseases.

This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.

In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes

Background: Neurodegenerative diseases can cause vision loss by damaging retinal ganglion cells in the optic nerve. Novel phosphine-borane compounds (PBs) can protect these cells from oxidative stress via the reduction of disulfide bonds. However, the specific targets of these compounds are unknown. Proteomic evidence suggests that myelin oligodendrocyte glycoprotein (MOG) is a potential target. MOG is of significant interest due to its role in anti-MOG optic neuritis syndrome. Methods: We used in silico modeling to explore the structural consequences of cleaving the extracellular domain MOG disulfide bond, both in isolation and in complex with anti-MOG antibodies. The potential binding of PBs to this bond was examined using molecular docking. Results: Cleaving the disulfide bond of MOG altered the structure of MOG dimers and reduced their energetic favorability by 46.13 kcal/mol. The energy profiles of anti-MOG antibody complexes were less favorable when the disulfide bond of MOG was reduced in the monomeric state by 55.21 kcal/mol, but the reverse was true in the dimeric state. PBs exhibited reducing capabilities with the MOG extracellular disulfide bond, with this best-scoring compound binding with an energy of −28.54 kcal/mol to the MOG monomer and −24.97 kcal/mol to the MOG dimer. Conclusions: These findings suggest that PBs can affect the structure of MOG dimers and the formation of antibody complexes by reducing the MOG disulfide bond. Structural changes in MOG could have implications for neurodegenerative diseases and anti-MOG syndrome.

Optic Neuritis - The Evolving Spectrum.

Optic neuritis (ON) is an inflammatory condition that affects the optic nerve and may be associated with various central nervous system demyelinating conditions, infectious diseases, and systemic autoimmune syndromes. This manuscript sheds light on the epidemiologic patterns and diverse clinical features of ON, emphasizing the importance of early detection and prompt treatment. Various studies have revealed geographic and ethnic variations across ON subtypes, which are likely related to the incidence and prevalence of co-associated disorders. Distinguishing ON subtypes may be challenging and requires use of paraclinical tools. Treatment strategies differ depending on the etiology, further highlighting the importance of accurately identifying specific ON subtypes in a timely manner.

Differential diagnosis of optic neuritis and anterior ischemic optic neuropathy

Background. Acute anterior ischemic neuropathy and optic neuritis are among the most common diseases that are the most frequent cause of both reversible and persistent visual acuity reduction. There is a sudden loss of vision, the clinical picture is often similar, and the restoration of visual functions and the prevention of complications in the form of optic nerve atrophy and disease relapses depend on a correct diagnosis and timely prescribed therapy. A significant level of medico-social and economic losses for society in all regions of the world is related to complications, namely the occurrence of optic nerve atrophy due to both optic nerve inflammation (neuritis) and ischemic optic neuropathy. The purpose was to determine the differential signs of optic neuritis and anterior ischemic optic neuropathy. Materials and methods. Eighty-five patients were examined, 52 (61.2 %) women and 33 (38.8 %) men. Seventy-one (83.5 %) participants were employed. The patients were divided into two groups: the first one — 38 patients with optic neuritis (papillitis); the second one — 47 people with ischemic optic neuropathy. General ophthalmological examinations were carried out. Results. Computed perimetry showed the presence of scotoma and quadrantanopia, both in anterior optic neuropathy (typical altitudinal scotomas) and optic neuritis (peripheral and central scotomas). The difference in the indicators of the electrical activity of the visual analyzer according to phosphene between the groups was 15.8 % (p < 0.05), which indicates a more significant increase in the functional activity of the visual analyzer in the group with anterior optic vascular neuropathy. Thinning of the peripapillar nerve fiber layer and partial atrophy of the optic nerve were noted 2 times less often in patients with anterior vascular ischemic neuropathy — 7 (16.3 %) vs. 14 (33.3 %) in those with partial atrophy of the optic nerve (Pearson’s χ2 = 22.59, p = 0.00001). Conclusions. The issue of early differential diagnosis of anterior optic ischemic neuropathy and optic neuritis is relevant, which determines the prognosis of the disease, allows increasing the effectiveness of treatment and preventing irreversible consequences. The therapeutic effect of treating the consequences of damage to the optic nerve is not stable and is weak, and success is not always achieved. First of all, the treatment of the underlying disease is indicated. Computed perimetry showed the presence of scotoma and quadrantanopia in both anterior optic neuropathy (typical altitudinal scotomas) and optic neuritis (peripheral and central scotomas).

Cognitive and academic outcomes in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

To describe the impact of paediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) on academic and cognitive outcomes. This was an observational, retrospective, and descriptive single-centre study, carried out on a paediatric case series of children with MOGAD. A total of 51 patients were included (22 females); their median age was 8 years and the median follow-up duration was 31.1 months (interquartile range 23.5). The most frequent clinical presentation was acute disseminated encephalomyelitis (54.9%), followed by optic neuritis (35.5%). At the last follow-up, regardless of the clinical phenotype at disease onset, 39.5% of patients with MOGAD received academic and educational interventions (p < 0.05 compared to before disease onset), including academic accommodations (p < 0.05) or the need for a learning support assistant (p < 0.05). Ten patients were evaluated with the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V). The overall IQ was calculated for six patients (mean = 92); two of these patients had an IQ lower than 85. No difference was found regarding prenatal and neonatal neurodevelopmental characteristics between this cohort and the general population. MOGAD was associated with a need for academic support; lower scores were found on the WISC-V. Patients with MOGAD should receive cognitive and academic assessments to inform educational planning and support academic success.

Central retinal artery occlusion as the initial manifestation of mixed connective tissue disease in a young woman: a case report

BackgroundRetinal artery occlusions are rare amongst young adults, and relevant risk factors and etiology remain unclear. In this report, we present a case of central retinal artery occlusion (CRAO) as the initial manifestation of mixed connective tissue disease (MCTD) in a young woman.Case presentationA 22-year-old female presented to the emergency department with a sudden decrease in visual acuity in her right eye for 1 hour. She reported a similar episode in her left eye five years prior, which resolved spontaneously after 2 hours. Initially misdiagnosed with optic neuritis in the right eye at another hospital, she was referred to our institution the following day. Clinical examination revealed a CRAO in her right eye. A detailed medical history revealed that she had developed livedo reticularis (LR) on both lower limbs five years ago, which had been overlooked and untreated. Further rheumatologic history, hematologic tests, and an autoimmune work-up confirmed a diagnosis of mixed connective tissue disease (MCTD).ConclusionIn young patients presenting with CRAO, further examinations should be conducted to investigate systemic disease or an embolic source to prevent future sequelae.

Optic neuritis in Rosai Dorfman disease.

A 55-year-old man while being evaluated for unexplained weight loss was found to have multiple metabolically active lymph nodes on positron emission tomography-computed tomography (PET-CT)scan, and biopsy from right axillary lymph node demonstrated multiple histiocytes with emperipolesis with S100 positivity, consistent with Rosai-Dorfman disease.

Demyelination and neurodegeneration early in experimental autoimmune encephalomyelitis contribute to functional deficits in the anterior visual pathway

Impaired visual function is a prevalent feature of optic neuritis (ON) in multiple sclerosis (MS). Abnormal visual evoked potential (VEP) findings of increased latencies, reduced amplitudes and abnormal waveforms as well as decreased retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT) are hallmarks of ON-induced visual dysfunction. Here we utilized the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to investigate the functional and pathological progression during early (before any clinical symptoms), peak (initial maximal clinical symptoms), and late (chronic disease for > 3 weeks) disease stages. Demyelination and initial stages of axon damage were observed in early EAE. Significant demyelination, inflammation, increased axon damage and impaired P1/N2 amplitudes and latencies by VEP were seen in middle and late EAE groups. A decrease in RNFL thickness by OCT was observed only during late EAE. NanoString analysis of optic nerves from late EAE indicated elevated inflammation-related genes, reduced myelin-related genes, and changes in axon degeneration-related genes. Early inflammatory demyelination and functional deficits of the visual pathway, if untreated, may lead to severe irrecoverable axon damage in EAE. These studies potentially help explain the progression of visual dysfunction during MS.

Optic Chiasmitis as an Isolated Manifestation of Myelin Oligodendrocyte Glycoprotein-Associated Disease – a Case Report

IntroductionThe most common cause of chiasmopathy is compression of the optic chiasm by parasellar tumours. The tumours may produce any pattern of visual field defect depending on the tumour location and the patient’s chiasmal anatomy. Rare, non-compressive causes of chiasmopathy include, among others, infectious, post-infectious, inflammatory, autoimmune, demyelinating, toxic and ischaemic processes. Chiasmopathy can also occur due to trauma and radiation treatment.Case reportWe report a case of a 43-year-old patient who was admitted to our department because of a two-month history of headaches and constant, symmetrical blurriness over the temporal sides of vision. After a wide-ranging diagnostic process, the patient was diagnosed with an isolated optic chiasmitis in the course of myelin oligodendrocyte glycoprotein-associated disease, which is a rare, monophasic or relapsing, antibody-mediated inflammatory demyelinating disorder of the central nervous system.ConclusionsIt is crucial to remember that parasellar tumours are not the only cause of bitemporal hemianopsia. Patients with bitemporal hemianopsia, if there is no compressive lesion of the optic chiasm, should be investigated for optic chiasmitis. Optic chiasmitis is not a diagnosis in itself, but a sign of an underlying pathology, and during its evaluation should be treated as a variation of atypical optic neuritis. We hope that this ophthalmic manifestation of a rare neurological disease will make other clinicians aware of the utter importance of careful evaluation of visual disturbances.

Ocular Syphilis: The Resurgence of an Old Disease Experience of a Tertiary Centre in Portugal

ABSTRACT Purpose To estimate the number of ocular syphilis (OS) cases diagnosed in a tertiary care centre in Portugal, correlate with increasing syphilis diagnoses and characterize the OS population. Materials and methods Retrospective, observational, single-center study that included patients diagnosed with OS between 2015 and 2023 at the local health unit of Coimbra. Demographic data were collected, and a complete ophthalmological examination was performed with multimodal imaging acquisition. Data on syphilis reports from the National System of Epidemiologic Surveillance were correlated with OS data. Results Fifty-four patients with OS were observed; mean age was 54.17 ± 14.46 years, 38 (70.37%) were male and 18 (47.37%) men who have sex with men. The proportion of OS in syphilis patients per year ranged from 0% to 10.34%. One-quarter were co-infected with HIV. Forty-nine patients (91.84%) complained of decreased visual acuity on presentation. Twenty-two (40.74%) had systemic findings (mostly skin rash). Two-thirds had bilateral disease and half presented with anterior segment involvement. Eighty-five percent had posterior segment involvement, mostly placoid chorioretinitis. Forty-one percent had optic nerve involvement. All patients were admitted and underwent 2-week treatment with intravenous penicillin. Visual acuity improved from logMAR 0.70 to logMAR 0.26 (p < 0.001). Conclusions Ocular syphilis is a heterogeneous disease with a wide range of presentations. The incidence is on the rise and therefore OS must be considered in every patient with anterior and posterior uveitis, panuveitis and optic neuritis, with or without systemic manifestations.

Leukemic occult infiltrative optic neuropathy presenting as optic neuritis: a case report

Isolated ocular relapses of leukemia are rare and typically present as infiltrative lesions of the optic nerve. This report presents a case of an isolated ocular relapse of leukemia in a female patient, characterized by occult infiltrative optic neuropathy. Despite the absence of leukemic cell infiltration on MRI, a 33-year-old female patient presented with optic neuritis, which resolved after intrathecal administration of chemotherapeutic agents. However, due to her non-compliance with the treatment regimen, leukemia progressed to infiltrative optic neuropathy. She refused radiation therapy, and while intrathecal injections provided temporary stabilization, they were insufficient for sustained disease control. This case uniquely documents the extended progression of an isolated ocular relapse of leukemia, evolving from an occult infiltrative lesion initially presenting as optic neuritis to a more pronounced infiltrative lesion. It suggests that leukemic optic nerve infiltration can occur in patients with leukemia even in the absence of MRI-detectable abnormalities. Radiation therapy emerges as a critical modality in the management of infiltrative lesions of the optic nerve.

Vitamin D levels and risk of ocular disorders: insights from bidirectional and multivariable Mendelian randomization analysis.

This study aimed to assess the causal relationships between vitamin D levels and ocular disorders. Independent genetic variables were obtained from genome-wide association studies (GWAS) and publicly available databases. The summary statistics for 25-hydroxyvitamin D (25(OH)D) were obtained from two large-scale GWAS studies, with sample sizes of 324,105 and 417,580 European individuals. The genetic variants of myopia, primary open angle glaucoma (POAG), anterior iridocyclitis, senile cataract, diabetic retinopathy (DR), retinal vein occlusion (RVO), wet age-related macular degeneration (WAMD) and optic neuritis were extracted from the latest release of FinnGen consortium, which contains genome data from Finnish participants. Subsequently, Mendelian randomization (MR) analyses were conducted to obtain effect estimates. Additionally, we performed multivariable MR analysis and mediation analysis to validate the results. In the discovery dataset, genetically predicted vitamin D concentration was found to be causally associated with an increased risk of WAMD, (odd ratio (OR) = 1.35, 95% confidence interval (CI) = 1.09-1.67, P IVW = 0.005). However, no causal effects of genetically predisposed vitamin D levels on the risk of most types of ocular disorders were observed. Reverse MR revealed no causal relationships between the ocular diseases and vitamin D concentrations. The MR analyses of the validation dataset yielded consistent results. Additionally, the causal effect of vitamin D levels on the risk of WAMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR = 1.86, 95% CI = 1.26-2.73, P IVW = 0.002). Our MR analysis results provide robust evidence of a causal relationship between genetically predicted 25(OH)D levels and an increased risk of WAMD in European population. These findings offer important insights into the management and control of ocular disorders.

Demographics, Etiologies, and Visual Outcomes in Pediatric Optic Neuritis at a Large Children’s Hospital

Demographics, Etiologies, and Visual Outcomes in Pediatric Optic Neuritis at a Large Children’s Hospital

Posterior Optic Neuropathies

Posterior optic neuritis refers to a group of rarer diseases of optic neuritis. Similar to anterior optic neuropathies, they can cause decreased visual acuity and optic nerve dysfunction. Although they can be caused by various causes, corticosteroids are important in their treatment. A multidisciplinary approach with ophthalmologists may be required in their management.

Paraneoplastic Optic Neuropathy

The paraneoplastic syndrome may occur in tissues that are distant from the primary malignancy or its metastasis and may include various signs and symptoms. It can negatively affect ocular tissues, which may threaten visual acuity, especially if it affects the retina and optic nerve. When it impacts the optic nerve, it is called paraneoplastic optic neuropathy. PON is a rare, subacute and progressive disease that can frequently affects both eyes. Its signs and symptoms can be very similar to other types of optic neuritis, which can lead to confusion and misdiagnosis. In this study, we aimed to outline the clinical features, pathogenesis, diagnosis, and management of PON.

6489 Type 1 Diabetes Mellitus And Multiple Sclerosis: A Case Report Showing The Concurrent Association Of Two Autoimmune Diseases

Abstract Disclosure: P.B. Singh: None. B. Sabates: None. A. Sharifzadeh: None. R.F. Rodriguez: None. Introduction: Both Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS) represent persistent autoimmune conditions. T1DM is characterized by the presence of specific autoantibodies targeting pancreatic β-cells. In MS, autoreactive cells mediate a demyelinating inflammatory response directed against the central nervous system. Despite differences in demographics and clinical characteristics, their common root in autoimmunity has led researchers to discover commonalities in genetic, environmental and immunological features. Case Presentation We present a case of a 40-year-old female with medical history of T1DM diagnosed at 7 years of age and MS diagnosed at 32 years of age. She presented to the hospital with clinical features of optic neuritis and symptoms of squeezing ribcage pressure consistent with acute MS exacerbation. After confirmatory neuroimaging, high-dose intravenous corticosteroids were initiated, and Endocrinology services were consulted for inpatient glycemic management. As the patient’s diabetes was treated via continuous subcutaneous insulin infusion (CSII), her pump settings were adjusted to maintain euglycemia during hospitalization. This case is reported to highlight and discuss the association between T1DM and MS. Discussion About 4-5% of the general population is affected by autoimmune disorders, among which T1DM and MS comprise a substantial portion. Multiple studies demonstrate the association and shared etiopathogenesis between T1DM and MS. One study revealed that the prevalence of T1DM is five times higher in patients with MS in comparison to the general population. In another prospective cohort study, individuals with T1DM had a three times higher chance of subsequently developing MS. Additionally, first-degree relatives of MS patients had a roughly 40% higher risk of developing T1DM. Women with T1DM had a 20-fold higher risk of having MS than women without the condition, per another study. As T-cell mediated autoimmune disorders, both T1DM and MS are characterized by autoantigen specific T1-helper cell responses, decreased T-cell suppressor activity, and the presence of various autoantibodies, some of which are seen in both diseases. One study showed that autoreactive T cells could target both pancreatic islet and central nervous system autoantigens in patients with MS, patients with T1DM, and relatives of patients with T1DM. Since MS- and T1DM-associated HLA haplotypes differ between populations, HLA class II alleles per se may not alone be responsible for disease susceptibility. It is suggested that variation at other non-HLA class II loci and/or unknown environmental factors might contribute significantly to the co-occurrence of these 2 diseases. In conclusion, individuals who already have one autoimmune condition are more likely to have other autoimmune conditions, with T1DM and MS being associated more often than expected. Presentation: 6/2/2024

Eyes as Windows: Unveiling Neuroinflammation in Multiple Sclerosis via Optic Neuritis and Uhthoff's Phenomenon.

Background/Objectives: This study investigated the frequency and timing of optic neuritis (ON) episodes in relation to the onset of multiple sclerosis (MS) and examined the occurrence of Uhthoff's phenomenon and Lhermitte's sign to understand their roles in early diagnosis and disease progression. Methods: A longitudinal study was conducted with 127 MS patients. Clinical data, including ophthalmological examinations for ON, were collected and questionnaires assessed the presence of Uhthoff's phenomenon and Lhermitte's sign. Results: Results showed that 37% of patients experienced demyelinating retrobulbar ON, with 25.53% having ON as the initial symptom of MS. Residual visual acuity impairment (below 20/40) and dyschromatopsia were reported by 25.53% and 17.02% of patients, respectively. Uhthoff's phenomenon and Lhermitte's sign were present in 26.77% and 36.22% of patients, respectively. The findings underscore the importance of early ophthalmological assessments in diagnosing MS, as ON can be an initial indicator of the disease. Conclusions: The study highlights the need for precise diagnostic tools and personalized therapeutic strategies focused on specific biomarkers and pathways involved in neuroinflammation and demyelination. Early diagnosis through vigilant ophthalmologic evaluation can lead to interventions that significantly alter disease progression, improving patient outcomes and quality of life.