Optic Neuritis Research Articles

Optociliary Shunt Vessels in Multiple Sclerosis.

Background/Introduction: Optociliary shunt vessels develop as a result of chronic retinal venous obstruction. Optic neuritis has never been reported as a causative influence. Cases: This case series follows two patients with multiple sclerosis from August 1st, 2019 to April 24th, 2024, who developed optociliary shunt vessels after attacks of optic neuritis. A 43-year-old female presented with left visual loss and bilateral superior optociliary shunt vessels. Perimetry showed bilateral peripheral visual field loss. Optical coherence tomography showed bilateral retinal thinning and ganglion cell complex loss. Optical coherence tomography angiography showed reduced capillary density bilaterally. We investigated her and eventually diagnosed her with multiple sclerosis. The second, 49-year-old female, developed right-sided optociliary shunt vessels after an episode of neuroretinitis. Perimetry revealed bilateral central scotomata; optical coherence tomography showed disc and retinal nerve fiber layer edema, and serous retinal detachment; later, ganglion cell complex loss; and reduced capillary density on optical coherence tomography angiography. Neuroimaging revealed demyelination in both, leading to a diagnosis of multiple sclerosis, and therapy was instituted. Conclusions: We hypothesize, that demyelinating optic neuritis due to multiple sclerosis causes chronic retinal hypoperfusion, leading to subsequent optociliary shunt development in affected eyes. Our case series reveals that eyes with optic neuritis, both previous episodes and fresh cases, can contribute to sufficient retinal vein hypoperfusion to cause the development of optociliary shunts, which should be reported in the literature.

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

Investigating the Relationship between Telomere-Related Gene Variants and Leukocyte Telomere Length in Optic Neuritis Patients

Optic neuritis (ON) is a condition marked by optic nerve inflammation due to various potential triggers. Research indicates a link between telomeres and inflammation, as studies demonstrate that inflammation can lead to increased telomere shortening. Aim: We aimed to determine the associations of telomere-related telomeric repeat binding factor 1 (TERF1) rs1545827, rs10107605, and telomeric repeat binding factor 2 (TERF2) rs251796 polymorphisms and relative leukocyte telomere length (LTL) with the occurrence of ON. Methods: In this research, a total of 73 individuals diagnosed with optic neuritis (ON) were studied and the control group included 170 individuals without any health issues. The DNA samples were obtained from peripheral blood leukocytes, which were purified using the DNA salting-out technique. Real-time polymerase chain reaction (RT-PCR) assessed single-nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (LTL). The data obtained were processed and analyzed using the “IBM SPSS Statistics 29.0” program. Results: Our study revealed the following results: in the male group, TERF2 rs251796 (AA, AG, and TT) statistically significantly differed between the long and short telomere group, with frequencies of 65.7%, 22.9%, and 2.0% in long telomeres, compared to 35.1%, 56.8%, and 8.1% in the short telomere group (p = 0.013). The TERF2 rs251796 CT genotype, compared to CC, under the codominant genetic model, was associated with 4.7-fold decreased odds of telomere shortening (p = 0.005). Meanwhile, CT+TT genotypes, compared to CC under the dominant genetic model, were associated with 3.5-fold decreased odds of telomere shortening (p = 0.011). Also, the CT genotype, compared to CC+TT, under the overdominant genetic model, was associated with 4.4-fold decreased odds of telomere shortening (p = 0.004). Conclusion: The current evidence may suggest a protective role of TERF2 rs251796 in the occurrence of ON in men.

Serum neurofilament light chain and glial fibrillary acidic protein for predicting response to apheresis in steroid-refractory multiple sclerosis relapses.

The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid-refractory multiple sclerosis (MS) relapse has not yet been evaluated. We used pre- and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid-refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays. Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635-0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903-0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965-2.069, p = 0.076). Analysis of the sNfL-to-sGFAP ratio showed an OR of 1.924 (95% CI = 1.073-3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis. Lower sGFAP levels, a higher sNfL-to-sGFAP ratio, and younger age are associated with a favourable apheresis outcome.

Disease Course of Clinically Isolated Optic Neuritis.

Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of visual pathway neuroprotection trials. This is a secondary analysis of longitudinal data from the TONE trial, which included 103 patients from 12 German academic tertiary centers with acute unilateral optic neuritis as a clinically isolated syndrome and baseline high-contrast visual acuity <0.5 decimal. Patients were randomized to 1,000 mg methylprednisolone i.v./d plus either erythropoietin (33,000 IU/d) or placebo (saline solution) for 3 days. They were followed up at standardized intervals with a battery of tests including high-contrast visual acuity, low-contrast letter acuity, contrast sensitivity, visual fields, visual evoked potentials, and retinal optical coherence tomography. At 6 months, participants answered a standardized questionnaire on vision-related quality of life (NEI-VFQ 25). We describe the disease course with mixed-effects piecewise linear models and calculate structure-function correlations using Pearson r. Because erythropoietin had no effect on the visual system, we use pooled (treatment-agnostic) data. Patients experienced initial rapid and then decelerating improvements of visual function with thinning of inner and thickening of outer retinal layers. At 6 months, visual parameters were positively correlated with inner and negatively correlated with outer retinal thickness changes. Peripapillary retinal nerve fiber layer thinning predominantly occurred in sectors without previous swelling. At 6 months, macular ganglion cell and inner plexiform layer thinning was weakly correlated with the P100 peak time (r = -0.11) and moderately correlated with the amplitude of visual evoked potentials (r = 0.35). Only functional outcomes were at least moderately correlated with vision-related quality of life. The longitudinal data from this large study cohort may serve as a reference for the clinical course of acute optic neuritis. The pattern of correlation between visual evoked potentials and inner retinal thinning may argue that the latter is mostly due to ganglion cell loss, rather than dysfunction. Visual pathway neuroprotection trials with functional outcomes are needed to confirm that candidate drugs will benefit patients' vision-related quality of life. ClinicalTrials.gov, NCT01962571.

Blood parameters in pediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) clinically present e.g. with acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM) or aquaporin-4-IgG (AQP4-IgG) negative neuromyelitis optica spectrum disorders (NMOSD)-like phenotypes. We aimed to analyze and compare blood parameters in children with MOGAD, AQP4-IgG-positive NMOSD (hence NMOSD), multiple sclerosis (MS) and healthy controls (HC). We evaluated differences in complete blood counts (CBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) between these four groups and within the groups between clinical attack, acute treatment and remission. Our cohort consisted of 174 children and adolescents with a total of 550 timepoints: 66 patients had MOGAD (202 timepoints), 11 NMOSD (76 timepoints), 58 MS (219 timepoints) and 39 were HC (53 timepoints). At clinical attack, leukocyte counts were elevated in MOGAD compared to remission (p<0.001) and compared to all other groups (p<0.001). NLR was high in MOGAD and NMOSD, and PLR was high in NMOSD, however, after correction for multiple testing these findings did not remain significant. While glucocorticoids caused an increase of leukocyte counts and NLR in NMOSD and MS, these values remained stable during acute treatment in MOGAD. In remission, NLR normalized in MOGAD, while it stayed high in NMOSD. PLR increased in NMOSD and was significantly higher compared to all other groups. Some blood parameters, mainly leukocyte and differential counts, might help clinicians to evaluate disease activity, differentiate relapses from pseudo-relapses and even distinguish between different disease entities.

Qualitative and Quantitative Magnetic Resonance Imaging in Bacterial Orbital Cellulitis

ABSTRACT Purpose To summarise the qualitative and quantitative parameters of bacterial orbital cellulitis (OC) on magnetic resonance imaging (MRI) and explore their clinical correlations. Methods Multi-centre retrospective study with inclusion of patients of all ages with OC who underwent MRI. Patients with isolated pre-septal cellulitis, bilateral disease and poor-quality scans were excluded. An enlargement ratio for extraocular muscles (EOMs) was calculated by dividing maximal EOM measurements from the affected side by the contralateral side. Results Twenty MRI scans from twenty patients (Mean age: 40.8 ± 24.3 years old, M: F = 15:5) between 2011 and 2022 were analysed. Three (15.0%) cases were paediatric patients (<18 years old). All cases had both pre-septal and orbital fat involvement. The EOM were affected in nineteen cases, with the superior muscle complex (18/19, 94.7%) most commonly affected. Mean enlargement ratio (1.30, Range: 1.04–1.82) was greatest for the medial rectus on axial views on T1 and fat-suppressed contrast-enhanced T1 (FS CE T1). Optic peri-neuritis was present in eleven (55.0%) patients, whilst two (9.5%) cases had optic neuritis. A greater degree of proptosis was observed in patients with optic neuropathy and those who underwent surgical intervention compared to those without (p = .002 and p = .002, respectively). Conclusion MRI remains an important imaging modality for evaluating complicated OC. However, qualitative features may lack accuracy and is not a reproducible means of analysis. Simple quantitative parameters, such as proptosis and EOM measurements, correlate with high-risk clinical features and may have utility in predicting clinical course.

Vaccines and the Eye: Current Understanding of the Molecular and Immunological Effects of Vaccination on the Eye

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

Optic neuritis and mydriasis after vaccination: a case report

BackgroundOptic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria.Case reportA 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months.ConclusionThis study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.

Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies. To address these knowledge gaps, we conducted a comprehensive 'stage-dependent' investigation of immune cell elements in situ in human NMOSD lesions, based on neuropathological techniques for autopsied/biopsied CNS materials. The present study provided three major findings. First, activated or netting neutrophils and melanoma cell adhesion molecule-positive (MCAM+) helper T (TH) 17/cytotoxic T (TC) 17 cells are prominent, and the numbers of these correlate with the size of NMOSD lesions in the initial or early-active stages. Second, forkhead box P3-positive (FOXP3+) regulatory T (Treg) cells are recruited to NMOSD lesions during the initial, early-active or late-active stages, suggesting rapid suppression of proinflammatory autoimmune events in the active stages of NMOSD. Third, compartmentalized resident memory immune cells, including CD103+ tissue-resident memory T (TRM) cells with long-lasting inflammatory potential, are detected under "standby" conditions in all stages. Furthermore, CD103+ TRM cells express high levels of granzyme B/perforin-1 in the initial or early-active stages of NMOSD in situ. We infer that stage-dependent compartmentalized immune traits orchestrate the pathology of anti-AQP4 antibody-guided NMOSD in situ. Our work further suggests that targeting activated/netting neutrophils, MCAM+ TH17/TC17 cells, and CD103+ TRM cells, as well as promoting the expansion of FOXP3+ Treg cells, may be effective in treating and preventing relapses of NMOSD.

Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review

Objective: Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. Methods: This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. Results: The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2–4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. Conclusion: The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Isolated Optic Neuritis: Etiology, Characteristics, and Outcomes in a US Mountain West Cohort.

The diagnosis and treatment of autoimmune optic neuritis (ON) has improved with the accessibility and reliability of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, yet autoantibody-negative ON remains common. This study describes the demographic, clinical, and outcome data in patients with isolated ON across the pediatric and adult cohort. A retrospective chart review of University of Utah Health patients with the International Classification of Diseases (ICD) code of ICD-9 377.30 (ON unspecified), ICD-9 377.39 (other ON), or ICD-10 H46 (ON) and at least 2 ophthalmologic evaluations were conducted between February 2011 and July 2023. Only isolated cases of ON without other brain or spinal demyelinating lesions were evaluated. Differences in demographic and clinical characteristics between AQP4, MOG, and Other-ON were determined. Of the 98 patients (15 children and 83 adults), 9 (9.2%) were positive for AQP4-IgG and 35 (35.7%) tested positive for MOG-IgG. Fifty-four were classified into Other-ON, of which 7 (13.0%) had recurrence or new demyelinating lesions during a median follow-up of 12.5 months-2 were ultimately diagnosed with recurrent isolated ON (RION), 1 with chronic relapsing inflammatory ON (CRION), 2 with multiple sclerosis, 1 with collapsin response-mediator protein (CRMP)-5-ON, and 1 with seronegative neuromyelitis optica spectrum disorder. Four patients were treated with long-term immunosuppressive therapy. No patients with RION or CRION had preceding infections; they had first recurrences of ON within 2 months. At presentation, AQP4-ON (75%) and MOG-ON (48.8%) had more severe vision loss (visual acuity <20/200) than Other-ON (23.2%, P = 0.01). At the 1-month follow-up, 93.0% of patients with MOG-ON and 89.3% of patients with Other-ON demonstrated a visual acuity ≥20/40, compared with only 50% of patients with AQP4-ON (P < 0.01). By the last follow-up, 37.5% of the AQP4-ON still exhibited visual acuity <20/40, including 25% who experienced severe vision loss (visual acuity <20/200). By contrast, over 95% of patients with MOG-ON and Other-ON maintained a visual acuity of ≥20/40. In our cohort, over a quarter of pediatric cases presented with simultaneous bilateral ON, 40% had a preceding infection, and 44.4% initially presented with a visual acuity <20/200. Two pediatric cases had recurrence, and both were MOG-ON. By their last follow-up, all pediatric cases had achieved a visual acuity of 20/40 or better. In addition, pediatric cases were more likely to exhibit disc edema compared with adult cases (100% vs 64%, P < 0.01). Despite recent advances in identification and availability of testing for AQP4-IgG and MOG-IgG, over half of patients who presented with isolated ON remained with an "idiopathic" diagnostic label. As more than 1 in 10 patients with AQP4-IgG and MOG-IgG negative ON experienced recurrence or develop new demyelinating lesions, clinicians should provide anticipatory guidance and closely monitor for potential long-term outcomes. In addition, it is crucial to re-evaluate the diagnosis in cases of poor recovery, ON recurrence, and the emergence of new neurological symptoms, as ON can often be the initial presentation of other conditions.

Optic chiasm involvement in multiple sclerosis, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein–associated disease

Background: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated. Aims: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON−) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers. Methods: Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied. Results: ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON− AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON− RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = −1.15, 95% confidence interval (CI) = −1.819 to −0.490, p = 0.001), worse visual acuity (RC = −0.026, 95% CI = −0.041 to −0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group. Conclusion: OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL.

[Leber's hereditary optic neuropathy].

Leber's hereditary optic atrophy (LHON) is a genetic optic neuropathy that is more prevalent in young males but can occur from childhood to old age. The primary cause is mitochondrial genetic mutations, which are associated with dysfunction of mitochondrial electron transport chain complex I. It manifests as acute to subacute visual impairment, often starting unilaterally but progressing to involve both eyes within weeks to months. Visual loss is severe, with many patients having corrected visual acuity below 0.1. The differential diagnosis of optic neuritis is essential, and assessments such as pupillary light reflex, fluorescein fundus angiography, and magnetic resonance imaging can be useful for differentiation. LHON should be considered as one of the differential diagnoses for optic neuritis, and collaboration between neurologists and ophthalmologists is crucial for accurate diagnosis and appropriate treatment.

Clinico-radiologic spectrum and outcome of paediatric acquired demyelinating disorders (ADS) of central nervous system: a retrospective Indian tertiary care hospital cohort.

Retrospective review of 70 children with ADS at tertiary-care hospital over 15 years (2008 to 2023) done. Diagnosis assigned as per International Paediatric Multiple Sclerosis Study Group criteria (IPMSSG)2016. Fisher-exact, chi-square test was applied. 39 boys,31 girls aged 8.2±4.0 years with CIS (n=27), ADEM (n=16), NMOSD (n=13), MS (n=1) and MOGAD (n=13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (76.9%) and aseptic meningitis (23%). Seropositivity for MOG-IgG was 62%, NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%) and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p=0.004), spinal cord (p=0.01) and cerebellar lesions (p=0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All received immunotherapy, 91.4% (n=64) had good recovery, 8.6% (n=6) had functional limitation on modified Rankin scale (mRS) at discharge. Twelve (17.1%) relapsed. Largest group was CIS. Seropositivity of MOG was high with atypical presentations like prolonged fever, aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favourable inspite of relapses.

Comparison of macular changes according to the etiology of optic neuritis: a cross-sectional study.

To compare the macular structure including foveal thickness among patients with optic neuritis (ON) according to the etiology and to investigate the possible correlation between structural and visual outcomes. In this retrospective cross-sectional study, the clinical data of patients with aquaporin-4 immunoglobulin G-related ON (AQP4 group, 40 eyes), myelin oligodendrocyte glycoprotein IgG-related ON (MOG group, 31 eyes), and multiple sclerosis-related ON (MS group, 24 eyes) were obtained. The retinal thickness of the foveal, parafoveal and perifoveal regions were measured. Visual acuity (VA), visual field index and mean deviation were measured as visual outcomes. The AQP4 group showed a significantly thinner fovea (226.4±13.4 µm) relative to the MOG (236.8±14.0 µm, P=0.015) and MS (238.9±14.3 µm, P=0.007) groups. The thickness in the parafoveal area also was thinner in the AQP4 group, though the difference in perifoveal retinal thickness was not significant. Foveal thickness was correlated with VA in the AQP4 group (coefficient ρ=-0.418, P=0.014), but not in the MOG and MS groups (P=0.218 and P=0.138, respectively). There was no significant correlation between foveal thickness and visual field test in all three groups. The significant thinning in the fovea and parafoveal areas in the AQP4 group compared to the MOG and MS groups are found. Additionally, macular changes in AQP4-ON show a significant correlation with VA. The results provide the possibility that retinal structural damage could reflect functional damage in AQP4-ON, distinct from MOG-ON and MS-ON.

PolySialic Acid Nanoparticles Actuate Complement-Factor-H-Mediated Inhibition of the Alternative Complement Pathway: A Safer Potential Therapy for Age-Related Macular Degeneration.

The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization.

Lactational optic neuritis - A case series with a review of the literature.

Optic neuritis is the most common optic neuropathy affecting adults, especially women. Lactational optic neuritis is a rare entity occurring during the postpartum period with a high chance of recurrence. Through this study, we evaluated the clinical profile and visual outcome of lactational optic neuritis. This was a retrospective study where patients with optic neuritis presenting during the first year of the postpartum period to the neuro-ophthalmology clinic between January 2016 and December 2022 were included in the study. This study included seven eyes of six patients. The mean age of presentation was 24.6 years, with all patients presenting after the first 3 months of the postpartum period. All patients had unilateral involvement except one, presenting with painful vision loss. Best corrected visual acuity ranged from 6/18 to hand movements. Relative afferent pupillary defect and dyschromatopsia were present in all patients. Disc edema was seen in all but one case. Three patients were treated with steroids along with multivitamins, and the remaining three refused treatment with steroids, receiving multivitamins alone. All patients had complete recovery by the end of 12 weeks. Optic neuritis during lactation is attributed more to post-pregnancy immunological changes rather than lactation itself. The presentation and clinical features are similar to classic optic neuritis and remain an important differential diagnosis for visual dysfunction in the postpartum period.

Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography.

We recruited four aquaporin-4 seropositive optic neuritis patients (five eyes) who received glucocorticoid treatment and underwent optical coherence tomography examination. Baseline medians of the macular ganglion cell layer plus inner plexiform layer (mGCIPL) thickness and volume for the eye of interest were 79.67 µm (73.664 ± 18.497 µm) and 0.58 mm3 (0.534 ± 0.134 mm3), respectively. At 2 months, the medians of the mGCIPL thickness and volume were 60.00 µm (51.576 ± 12.611 µm) and 0.44 mm3 (0.376 ± 0.091 mm3), respectively. At 6 months, the medians of the mGCIPL thickness and volume were 59.55 µm (46.288 ± 11.876 µm) and 0.44 mm3 (0.336 ± 0.084 mm3), respectively. Sample size estimate was achieved using two methods based on the mGCIPL thickness and volume data, with five effect sizes considered. The estimate based on the mGCIPL volume showed that 206 patients were needed at the 6-month follow-up; the power was 80% and effect size was 20%. In conclusion, this study detected retinal damage in aquaporin-4 seropositive optic neuritis patients by optical coherence tomography, and estimated the sample size for two-sample parallel designed clinical trials using two methods.

Applying the 2022 optic neuritis criteria to noninflammatory optic neuropathies with optic nerve T2-hyperintensity: an observational study.

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. 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. 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. 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.