Acute Optic Neuritis Network: an International Study That Invesitages Subjects With a First-ever Episode of Acute Inflammation of the Optic Nerve

Study Overview
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Brief Summary
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The goal of this observational study is to longitudinally investigating subjects with inaugural acute optic neuritis (ON). The main questions it aims to answer are: Does the time to corticosteroid treatment affect the visual outcome at 6 months in subjects with acute multiple sclerosis (MS)-, aquaporin 4-IgG positive (AQP4-IgG+) and myelin-oligodendrocyte-glycoprotein-IgG positive (MOG-IgG+) ON? How differ clinical, structural, and laboratory biomarkers in subjects with acute ON, including clinical isolated syndrome (CIS), MS-ON, AQP4-IgG+ON, MOG-IgG+ON and seronegative non-MS-ON? Participants will undergo clinical examination, including clinical history, neurovisual and neurological tests serum and cerebrospinal fluid examination optical coherence tomography (OCT) magnetic resonance imaging (MRI) assessment of depression, pain, quality of life through validated questionnaires Researchers will compare subjects with MS-ON, AQP4-IgG+ON, MOG-IgG+ON and other ON (CIS, seronegative non-MS-ON) to detect diagnostic and predictive markers for the disease course.

Detailed Description
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The Acute Optic Neuritis Network (ACON) is a global cooperation of currently 26 academic centers longitudinally investigating subjects with inaugural acute optic neuritis (ON). ON often occurs at presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin-oligodendrocyte-glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North-American study population, which did not address treatment timing, or antibody serostatus. The ACON study is primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. All patients presenting within 30 days of inaugural ON will be enrolled. For primary analysis, patients will subsequently be assigned either into the MS-ON, aquaporin-4-IgG positive ON (AQP4-IgG+ON) or MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from onset of visual loss to high-dose corticosteroids. The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. Additionally, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include: optical coherence tomography (OCT) and magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4- and MOG-IgG levels; neurofilament; glial fibrillary protein), questionnaires (headache, visual function in daily routine, depression, and quality of life) at presentation, at 6- and 12-months follow-up. Data will be collected from 22 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, Australia and Europe. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and accuracy of diagnostic stratification in acute demyelinating ON.

Official Title
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The Acute Optic Neuritis Network (ACON): a Non-interventional Prospective Multicenter Study on Diagnosis and Treatment of Acute Optic Neuritis

Conditions
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Demyelinating Diseases, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder Attack, Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Optic Neuritis

Intervention / Treatment
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* Other: non-interventional study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First-ever acute ON Onset of visual symptoms within maximum of 30 days Age ≥ 18 years Ability to give written informed consent Presence of written consent Exclusion Criteria: MRI contraindication Prior demyelinating diagnosis Diagnosis of other forms of optic neuropathy (hereditary, granulomatous, infectious, infiltrative, toxic) Pregnancy at inclusion Relevant other diseases that conflict with study participation according to protocol Inability to cooperate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: non-interventional study|observational study|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to investigate whether MS-ON, AQP4-IgG+ON and MOG-IgG+ON patients treated with early high-dose corticosteroids for visual loss have better visual outcomes and QoL than those with late treatment. | visual acuity | Six months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment. | RNFL | Six months follow-up | 
| Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment. | MRI lesion score | Six months follow-up | 
| Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment. | MRI lesion score | 12 months follow-up | 
| Visual and structural outcomes of MS-ON in patients treated with high-dose corticosteroid-therapy with oral prednisone taper vs. without taper as standard of care. | RNFL | 12 months follow-up | 
| Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. | NfL (pg/ml) | Acute stage (onset) | 
| Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. | GFAP (pg/ml) | Acute stage (onset) | 
| Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. | NfL (pg/ml) | Six months follow-up | 
| Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. | GFAP (pg/ml) | Six months follow-up | 
| Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. | NfL (pg/ml) | 12 months follow-up | 
| Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. | GFAP (pg/ml) | 12 months follow-up | 
| Characterization of MOG-IgG and AQP4-IgG levels and compartmentalisation (serum vs. CSF, using simultaneous paired samples) and associated risks for subsequent relapses in subjects with AQP4-IgG+ON and MOG-IgG+ON. | MOG-IgG ratio | Acute stage (onset) | 
| Characterization of MOG-IgG and AQP4-IgG levels and compartmentalisation (serum vs. CSF, using simultaneous paired samples) and associated risks for subsequent relapses in subjects with AQP4-IgG+ON and MOG-IgG+ON. | AQP4-IgG ratio | Acute stage (onset) | 
| Characterization of MOG-IgG and AQP4-IgG levels and compartmentalisation (serum vs. CSF, using simultaneous paired samples) and associated risks for subsequent relapses in subjects with AQP4-IgG+ON and MOG-IgG+ON. | MOG-IgG IgG ratio | Six months follow-up | 
| Characterization of MOG-IgG and AQP4-IgG levels and compartmentalisation (serum vs. CSF, using simultaneous paired samples) and associated risks for subsequent relapses in subjects with AQP4-IgG+ON and MOG-IgG+ON. | AQP4-IgG ratio | 12 months follow-up | 
| Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD. | pRNFL | Acute stage (onset) | 
| Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD. | pRNFL | Six months follow-up | 
| Prognostic value of OCT markers (e.g. increased pRNFL) for the visual outcome at 1-year follow-up. | pRNFL | 12 months follow-up | 
| Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS. | OCT markers | Acute stage (onset) | 
| Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS. | OCT markers | Six months follow-up | 
| Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS. | OCT markers | 12 months follow-up | 
| Diagnostic value of early clinical variables (i.e. visual loss and pain patterns). | pain intensity | Acute stage (onset) | 
| Diagnostic value of early clinical variables (i.e. visual loss and pain patterns). | pain intensity | Six months follow-up | 
| Diagnostic value of early clinical variables (i.e. visual loss and pain patterns). | pain intensity | 12 months follow-up | 
| Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. | NEI-VFQ-Score | Six months follow-up | 
| Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. | NEI-VFQ-Score | 12 months follow-up | 
| Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. | BDI-II Score | Six months follow-up | 
| Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. | BDI-II Score | 12 months follow-up | 
| Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. | EuroQol 5-Dimension EQ-5D-index | Six months follow-up | 
| Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. | EuroQol 5-Dimension EQ-5D-index | 12 months follow-up |