Optic Neuritis

Neurological Disorder MONDO:0005885 Pathograph 14 Autoimmune Disorder Demyelinating Disease Eye disorder

Optic neuritis is an inflammatory optic neuropathy in which immune-mediated injury of the optic nerve causes acute or subacute visual dysfunction. Modern classification treats optic neuritis as a heterogeneous syndrome: it can be isolated, multiple sclerosis-associated, MOG-IgG-associated, AQP4-IgG neuromyelitis optica spectrum disorder-associated, or linked to other systemic, infectious, or inflammatory disorders. Accurate etiologic attribution at the first attack is clinically important because acute treatment, relapse prevention, and prognosis differ across subgroups.

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1
Mappings
3
Definitions
4
Pathophys.
13
Phenotypes
14
Pathograph
4
Treatments
6
Subtypes
3
Differentials
6
Trials
26
References
1
Deep Research
🔗

Mappings

MONDO
MONDO:0005885 optic neuritis
skos:exactMatch MONDO
Primary MONDO disease term for the broad optic neuritis entry.
📘

Definitions

3
Autoimmune optic neuritis spectrum
Autoimmune optic neuritis is a heterogeneous inflammatory optic-nerve syndrome spanning multiple sclerosis, NMOSD, MOGAD, isolated optic neuritis, and other etiologies. First-attack attribution should combine clinical red flags with orbital MRI, antibody assays, OCT, visual evoked potentials, and selected fluid biomarkers.
CASE_DEFINITION
Multimodal first-attack attribution
Core clinical characteristics
  • optic neuritis
  • visual loss
Show evidence (1 reference)
PMID:41688447 SUPPORT Human Clinical
"Early and accurate attribution at the first attack is clinically decisive"
The 2026 review frames autoimmune optic neuritis as a heterogeneous spectrum whose first-attack attribution affects treatment choice.
International optic neuritis diagnostic-classification framework
The 2022 international framework begins with clinical features sufficient for possible optic neuritis, then uses paraclinical tests including brain, orbital, and retinal imaging, antibody testing, and protein biomarkers to support definite optic neuritis and classify disease subgroups.
DIAGNOSTIC_CRITERIA
Show evidence (1 reference)
PMID:36179757 SUPPORT Human Clinical
"developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups"
Petzold et al. provide the consensus classification framework used to distinguish optic neuritis subgroups.
Orphanet isolated optic neuritis definition
Isolated optic neuritis consists of single or recurrent optic neuritis episodes not associated with another neurologic or systemic disease.
OTHER
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"isolated episodes (either single or recurrent) of optic neuritis"
Orphanet defines the isolated subtype by single or recurrent attacks in the absence of another neurologic or systemic disorder.
◆

Subtypes

6
Isolated optic neuritis MONDO:0044688
Optic neuritis occurring as isolated single or recurrent attacks without another neurologic or systemic disease explaining the presentation.
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"not associated with other neurological or systemic disease"
Orphanet explicitly defines isolated optic neuritis by absence of an associated neurologic or systemic disease.
Single isolated optic neuritis MONDO:0971049
A monophasic isolated optic neuritis attack without recurrent optic neuritis during follow-up.
Show evidence (1 reference)
ORPHA:659626 SUPPORT Other
"Single isolated optic neuritis"
Orphanet records single isolated optic neuritis as a clinical subtype of isolated optic neuritis.
Relapsing isolated optic neuritis MONDO:0971050
Recurrent isolated optic neuritis attacks without another identified neurologic or systemic disease driver.
Show evidence (2 references)
ORPHA:659634 SUPPORT Other
"Relapsing isolated optic neuritis"
Orphanet records relapsing isolated optic neuritis as a clinical subtype of isolated optic neuritis.
PMID:30612145 SUPPORT Human Clinical
"monitoring for recurrence is needed even in patients with a single episode"
Adult follow-up data support recurrence as a clinically important course pattern after a first optic neuritis episode.
Multiple sclerosis-associated optic neuritis
Optic neuritis attributable to multiple sclerosis, often a first demyelinating event requiring MS-specific prognostic assessment and disease-modifying treatment decisions.
Show evidence (1 reference)
PMID:36179757 SUPPORT Human Clinical
"timely treatment of individuals with multiple sclerosis"
The international classification paper identifies multiple sclerosis as a key etiologic subgroup requiring early attribution.
MOG-IgG-associated optic neuritis
Optic neuritis occurring within MOG antibody-associated disease, commonly presenting as acute optic neuritis and often requiring MOGAD-specific relapse-risk assessment.
Show evidence (2 references)
PMID:36706773 SUPPORT Human Clinical
"MOGAD is typically associated with acute disseminated encephalomyelitis, optic neuritis, or transverse myelitis"
The international MOGAD criteria establish optic neuritis as a typical MOGAD phenotype.
PMID:38783085 SUPPORT Human Clinical
"MOGAD most frequently presents with optic neuritis"
The MOG-ON review supports optic neuritis as the most frequent MOGAD presentation and describes bilateral involvement, disc swelling, and longitudinally extensive optic nerve hyperintensity as distinguishing features.
AQP4-IgG/NMOSD-associated optic neuritis
Optic neuritis caused by AQP4-IgG-positive neuromyelitis optica spectrum disorder. Attacks can be severe, may involve long optic-nerve segments or the chiasm, and should prompt NMOSD-specific relapse prevention.
Show evidence (1 reference)
PMID:26092914 SUPPORT Human Clinical
"clinical syndromes or MRI findings related to optic nerve"
The NMOSD criteria identify optic-nerve involvement as a core clinical characteristic in AQP4-IgG-positive disease.
⚙

Pathophysiology

4
Immune-mediated optic nerve inflammation
Optic neuritis is driven by inflammatory injury within the optic nerve, producing acute or subacute visual dysfunction. The broad syndrome includes isolated inflammatory optic neuropathy as well as disease-specific immune mechanisms in MS, MOGAD, NMOSD, and systemic inflammatory disease.
inflammatory response link ↑ INCREASED neuroinflammatory response link ↑ INCREASED
cranial nerve II link
Downstream
Optic Nerve Conduction Delay Inflammation and demyelination delay optic pathway conduction, which can be measured with visual evoked potentials.
Visual Dysfunction Optic nerve inflammation causes visual acuity loss, dyschromatopsia, visual field defects, and reduced contrast sensitivity.
Show evidence (2 references)
ORPHA:499096 SUPPORT Other
"A rare inflammatory optic neuropathy"
The Orphanet structured record anchors the isolated form as inflammatory optic neuropathy.
PMID:41688447 SUPPORT Human Clinical
"Autoimmune optic neuritis (ON) is a heterogeneous spectrum"
The 2026 review supports heterogeneous immune-mediated etiologies for optic neuritis.
Inflammatory demyelinating optic neuropathy
Many optic neuritis attacks are demyelinating optic neuropathies. Loss or dysfunction of optic nerve myelin slows visual pathway conduction and is reflected by prolonged visual evoked potential latency; retinal and optic nerve structural injury can be followed by OCT.
oligodendrocyte link
myelination link ↓ DECREASED
myelin sheath link
cranial nerve II link
Downstream
Visual Evoked Potential Latency Prolongation Demyelinating injury slows optic nerve conduction and prolongs P100 or full-field VEP latency.
Show evidence (2 references)
clinicaltrials:NCT01524250 SUPPORT Human Clinical
"acute demyelinating optic neuritis"
The randomized oral-versus-intravenous corticosteroid trial record specifically enrolled acute demyelinating optic neuritis.
PMID:28229892 SUPPORT Human Clinical
"measured as recovery of affected optic nerve conduction latency"
RENEW used optic nerve conduction latency recovery as a remyelination endpoint, linking optic neuritis to demyelinating conduction delay.
MOG-IgG-mediated demyelinating optic neuritis
In MOGAD-associated optic neuritis, antibodies to conformational MOG epitopes identify a demyelinating disease that is distinct from MS and AQP4-IgG NMOSD. MOG-IgG effector mechanisms include complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and T-cell supported CNS inflammation.
complement activation link ↑ INCREASED T cell mediated immunity link ↑ INCREASED
Downstream
Inflammatory Demyelinating Optic Neuropathy MOG-IgG effector mechanisms converge on oligodendrocyte/myelin injury in optic neuritis attacks.
Show evidence (2 references)
PMID:36706773 SUPPORT Human Clinical
"Serum antibodies directed against myelin oligodendrocyte glycoprotein"
International criteria establish serum MOG-IgG as the defining biomarker for MOGAD, a common optic neuritis etiology.
PMID:40088708 SUPPORT Human Clinical
"MOG-IgG-mediated demyelination occurs via complement-dependent cytotoxicity"
The review describes antibody effector mechanisms relevant to MOGAD optic neuritis.
AQP4-IgG astrocytopathic optic neuritis
In AQP4-IgG-positive NMOSD, optic neuritis reflects astrocyte-targeted autoimmunity with complement-mediated injury and secondary demyelination. This mechanism differs from primary MS-type demyelination and from MOGAD.
astrocyte link
AQP4 link
complement activation, classical pathway link ↑ INCREASED
Downstream
Secondary Demyelination and Neuronal Injury Complement-mediated astrocyte injury propagates demyelinating and axonal damage in optic pathways.
Show evidence (1 reference)
PMID:26092914 SUPPORT Human Clinical
"associated with serum aquaporin-4 immunoglobulin G antibodies"
The NMOSD consensus criteria establish AQP4-IgG as the defining serologic marker for the AQP4-positive optic neuritis subgroup.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Referential integrity issues (6):
  • Target 'Optic Nerve Conduction Delay' (from 'Immune-mediated optic nerve inflammation') not found in named elements
  • Target 'Visual Dysfunction' (from 'Immune-mediated optic nerve inflammation') not found in named elements
  • Target 'Visual Evoked Potential Latency Prolongation' (from 'Inflammatory demyelinating optic neuropathy') not found in named elements
  • Target 'Inflammatory Demyelinating Optic Neuropathy' (from 'MOG-IgG-mediated demyelinating optic neuritis') not found in named elements
  • Target 'Secondary Demyelination and Neuronal Injury' (from 'AQP4-IgG astrocytopathic optic neuritis') not found in named elements
  • ... and 1 more
Pathograph: causal mechanism network for Optic Neuritis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

13
Eye 6
Optic Neuritis VERY_FREQUENT Optic neuritis (HP:0100653)
Show evidence (1 reference)
PMID:36179757 SUPPORT Human Clinical
"diagnostic criteria for optic neuritis"
Optic neuritis is the defining phenotype and the target of the diagnostic classification framework.
Bilateral Optic Neuritis FREQUENT Optic neuritis (HP:0100653)
Show evidence (1 reference)
PMID:38783085 SUPPORT Human Clinical
"Bilateral involvement, disc swelling clinically and radiologically"
The 2024 MOG-ON review identifies bilateral involvement and disc swelling as characteristic features that help distinguish MOG-associated optic neuritis from other etiologies.
Visual Loss COMMON Visual loss (HP:0000572)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"subacute unilateral loss of vision"
Orphanet lists subacute unilateral visual loss as a typical presentation of isolated optic neuritis.
Visual Field Defect VERY_FREQUENT Visual field defect (HP:0001123)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"Visual field defect"
Orphanet annotates visual field defect as very frequent in isolated optic neuritis.
Central Scotoma FREQUENT Central scotoma (HP:0000603)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"Central scotoma"
Orphanet annotates central scotoma as frequent in isolated optic neuritis.
Photopsia OCCASIONAL Photopsia (HP:0030786)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"light flashes on eye movement"
Orphanet annotates photopsia as occasional in isolated optic neuritis.
Constitutional 1
Ocular Pain VERY_FREQUENT Ocular pain (HP:0200026)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"periocular pain"
Orphanet annotates ocular pain as very frequent in isolated optic neuritis.
Other 6
Eye Movement-Induced Pain VERY_FREQUENT Eye movement-induced pain (HP:0030857)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"pain on eye movement"
Orphanet annotates eye movement-induced pain as very frequent in isolated optic neuritis.
Dyschromatopsia VERY_FREQUENT Dyschromatopsia (HP:0007641)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"abnormal color vision"
Orphanet annotates dyschromatopsia as very frequent in isolated optic neuritis.
Reduced Contrast Sensitivity VERY_FREQUENT Reduced contrast sensitivity (HP:0032036)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"reduced contrast sensitivity"
Orphanet annotates reduced contrast sensitivity as very frequent in isolated optic neuritis.
Marcus Gunn Pupil FREQUENT Marcus Gunn pupil (HP:0200057)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"relative afferent pupillary defect"
Orphanet lists relative afferent pupillary defect and annotates Marcus Gunn pupil as frequent.
Optic Disc Swelling FREQUENT Abnormal optic disc morphology (HP:0012795)
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"optic disc appears swollen"
Orphanet lists swollen optic disc as a frequent isolated optic neuritis feature; HP:0012795 is used as the closest HPO parent because papilledema specifically denotes optic disc swelling from raised intracranial pressure.
Abnormal Visual Evoked Potentials Abnormality of visual evoked potentials (HP:0000649)
Show evidence (1 reference)
PMID:29507942 SUPPORT Human Clinical
"P100 component of the visual evoked potential"
The randomized corticosteroid trial used VEP P100 latency recovery as a primary optic nerve function outcome.
💊

Treatments

4
Acute high-dose corticosteroids
Action: systemic corticosteroid therapy Ontology label: Systemic Corticosteroid Therapy NCIT:C122080
Agent: corticosteroid ↗
High-dose corticosteroids, usually intravenous methylprednisolone or a bioequivalent high-dose oral regimen, accelerate recovery in acute optic neuritis. Low-dose oral prednisone alone, as used in the original ONTT, is not equivalent and increased new optic neuritis episodes.
Mechanism Target:
INHIBITS Immune-mediated optic nerve inflammation — High-dose corticosteroids suppress acute inflammatory optic nerve injury and speed visual recovery.
Show evidence (3 references)
PMID:1734247 SUPPORT Human Clinical
"Visual function recovered faster in the group receiving intravenous methylprednisolone"
ONTT supports high-dose intravenous methylprednisolone for faster visual recovery in acute optic neuritis.
PMID:29507942 SUPPORT Human Clinical
"bioequivalent doses of oral corticosteroids may be used as an alternative to IV corticosteroids"
This randomized trial supports bioequivalent high-dose oral corticosteroids as an alternative route to high-dose IV therapy.
PMID:1734247 REFUTE Human Clinical
"Oral prednisone alone, as prescribed in this study, is an ineffective treatment"
The ONTT finding distinguishes high-dose steroid treatment from low-dose oral prednisone monotherapy.
Plasma exchange escalation for severe or steroid-refractory optic neuritis
Action: plasmapheresis Ontology label: Plasmapheresis NCIT:C15304
Therapeutic plasma exchange is considered for severe or steroid-refractory optic neuritis, especially in NMOSD/AQP4-associated attacks. Evidence is strongest in observational NMO/NMOSD relapse cohorts, while aggregate data specific to acute NMO/NMOSD optic neuritis remain limited.
Mechanism Target:
INHIBITS AQP4-IgG/NMOSD-associated optic neuritis — Plasma exchange removes circulating pathogenic antibodies and complement mediators during severe antibody-associated attacks.
Show evidence (4 references)
PMID:25921047 SUPPORT Human Clinical
"PLEX+IVMP are more likely to improve EDSS after NMO relapses"
This NMO/NMOSD relapse cohort supports adding plasma exchange to high-dose steroids, including relapses involving the optic nerves.
PMID:36822570 SUPPORT Human Clinical
"Most ON attacks improved with PLEX"
The 395-attack international cohort supports PLEX as a clinically useful escalation therapy for severe optic neuritis and identifies delayed PLEX as a poor-outcome predictor.
PMID:15452303 SUPPORT Human Clinical
"PE may be beneficial as an escalating treatment"
This severe optic neuritis case series supports plasma exchange as an escalation option when high-dose steroids are insufficient.
+ 1 more reference
Maintenance intravenous immunoglobulin for relapsing MOGAD-associated optic neuritis
Action: intravenous immunoglobulin therapy Ontology label: immunoglobulin infusion therapy MAXO:0001480
Maintenance IVIG is used as a relapse-prevention option in relapsing MOGAD, including patients whose MOGAD phenotype includes optic neuritis. Evidence is retrospective and subtype-specific rather than a general treatment for all optic neuritis.
Mechanism Target:
INHIBITS MOG-IgG-mediated demyelinating optic neuritis — IVIG is used to reduce relapsing MOG-IgG-associated inflammatory demyelinating attacks.
Show evidence (1 reference)
PMID:35377395 SUPPORT Human Clinical
"maintenance IVIG was associated with a reduction in disease relapse"
This international adult MOGAD cohort supports maintenance IVIG as a relapse-prevention strategy relevant to relapsing MOG-associated optic neuritis.
Eculizumab relapse prevention for AQP4-IgG/NMOSD-associated optic neuritis
Action: Pharmacotherapy NCIT:C15986
Agent: eculizumab ↗
Complement C5 blockade with eculizumab reduces relapse risk in AQP4-IgG-positive NMOSD; this is relevant to optic neuritis when optic nerve attacks occur as part of AQP4-IgG/NMOSD-associated disease.
Mechanism Target:
INHIBITS AQP4-IgG astrocytopathic optic neuritis — C5 blockade reduces terminal complement-mediated astrocyte injury in AQP4-IgG-positive NMOSD.
Show evidence (1 reference)
PMID:31050279 SUPPORT Human Clinical
"Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group"
The PREVENT trial supports eculizumab for relapse prevention in AQP4-IgG-positive NMOSD, including prevention of recurrent optic neuritis attacks in that subtype context.
🔬

Biochemical Markers

3
MOG-IgG seropositivity (PRESENT)
Context: Serum MOG-IgG identifies MOGAD-associated optic neuritis and should be interpreted with assay quality, titer, and phenotype in mind.
Show evidence (1 reference)
PMID:36706773 SUPPORT Human Clinical
"presence of MOG-IgG is a core criterion"
International MOGAD criteria define MOG-IgG as a core diagnostic criterion for MOGAD-associated optic neuritis.
AQP4-IgG seropositivity (PRESENT)
Context: Serum AQP4-IgG identifies NMOSD-associated optic neuritis and strongly changes relapse-prevention and acute-attack management.
Show evidence (1 reference)
PMID:26092914 SUPPORT Human Clinical
"NMOSD with or without AQP4-IgG"
The NMOSD consensus framework stratifies disease by AQP4-IgG serostatus.
Serum neurofilament light chain and serum GFAP (INCREASED)
Context: Serum neurofilament light chain and serum glial fibrillary acidic protein are emerging injury biomarkers that may help refine risk estimates, particularly in seronegative or diagnostically gray-zone optic neuritis.
Show evidence (1 reference)
PMID:41688447 SUPPORT Human Clinical
"may refine risk estimates, especially in seronegative cases"
The 2026 review identifies sNfL and sGFAP as emerging adjunct biomarkers for risk estimation in autoimmune optic neuritis.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Optic Neuritis:

Nonarteritic anterior ischemic optic neuropathy
Overlapping Features Ischemic optic neuropathy is a common optic neuritis mimic in referred patients and should be considered when age, vascular risk factors, disc appearance, pain pattern, and imaging are atypical for inflammatory optic neuritis.
Distinguishing Features
  • Often painless sudden vision loss rather than subacute painful inflammatory visual loss.
  • Optic disc findings and vascular risk profile may favor ischemic neuropathy.
Show evidence (1 reference)
PMID:29222573 SUPPORT Human Clinical
"other optic neuropathies, particularly nonarteritic anterior ischemic optic neuropathy"
The overdiagnosis study identifies nonarteritic anterior ischemic optic neuropathy as a frequent alternative diagnosis.
Headache, ocular pain, and functional visual loss mimics
Overlapping Features Headache syndromes, eye pain without optic nerve inflammation, and functional visual loss can be misclassified as optic neuritis when isolated history items are overweighted.
Distinguishing Features
  • Normal objective afferent visual pathway findings argue against optic neuritis.
  • A single symptom such as eye pain should not substitute for optic nerve evidence.
Show evidence (1 reference)
PMID:29222573 SUPPORT Human Clinical
"headache and eye pain, functional visual loss"
These were among the most common alternative diagnoses in patients referred with suspected acute optic neuritis.
Infectious and systemic inflammatory optic neuropathies
Overlapping Features Infectious optic neuropathies and systemic inflammatory diseases such as sarcoidosis, SLE, Behcet disease, and vasculitis can produce optic neuritis or optic neuropathy and require targeted evaluation when clinical context or imaging is atypical for MS, MOGAD, NMOSD, or isolated optic neuritis.
Distinguishing Features
  • Systemic symptoms, uveitis, granulomatous disease, vascular inflammation, or infectious exposure can redirect evaluation.
  • Etiology-specific treatment may be required beyond acute corticosteroids.
Show evidence (1 reference)
PMID:41688447 SUPPORT Human Clinical
"and other etiologies"
The 2026 review frames autoimmune optic neuritis as a spectrum that includes other etiologies beyond MS, NMOSD, and MOGAD.
🔬

Clinical Trials

6
NCT00000146 PHASE_III UNKNOWN
Historic Optic Neuritis Treatment Trial evaluating corticosteroid treatment, natural history, and MS risk after optic neuritis.
Show evidence (2 references)
clinicaltrials:NCT00000146 SUPPORT Human Clinical
"To assess the beneficial and adverse effects of corticosteroid treatment for optic neuritis."
The ClinicalTrials.gov record documents the ONTT corticosteroid treatment and natural-history objectives.
PMID:1734247 SUPPORT Human Clinical
"randomly assigned 457 patients with acute optic neuritis"
The NEJM publication reports the pivotal ONTT corticosteroid trial.
NCT01524250 PHASE_III COMPLETED
Randomized single-blind trial comparing bioequivalent high-dose oral versus intravenous corticosteroids for acute demyelinating optic neuritis.
Show evidence (2 references)
clinicaltrials:NCT01524250 SUPPORT Human Clinical
"randomized to receive equivalent doses of either intravenous (IV) or oral corticosteroid treatment"
The trial record documents the randomized oral-versus-IV corticosteroid comparison.
PMID:29507942 SUPPORT Human Clinical
"no significant difference between groups"
The published trial found no significant recovery difference between bioequivalent oral and IV high-dose corticosteroids.
NCT01721161 PHASE_II COMPLETED
RENEW randomized placebo-controlled phase 2 trial of BIIB033/opicinumab after first unilateral acute optic neuritis, evaluating remyelination by visual evoked potential latency recovery.
Show evidence (2 references)
clinicaltrials:NCT01721161 SUPPORT Human Clinical
"evaluate the efficacy of BIIB033 in subjects with their first episode of unilateral acute optic neuritis"
The trial record documents the RENEW acute optic neuritis study.
PMID:28229892 PARTIAL Human Clinical
"Remyelination did not differ significantly between the opicinumab and placebo groups"
RENEW was mechanistically important but did not meet the primary intention-to-treat remyelination endpoint.
NCT02657915 PHASE_II COMPLETED
RENEWED follow-up study assessing long-term electrophysiologic and clinical outcomes in participants from the RENEW opicinumab acute optic neuritis trial.
Show evidence (2 references)
clinicaltrials:NCT02657915 SUPPORT Human Clinical
"assess full-field visual evoked potential (FF-VEP) latency"
The trial record documents the long-term VEP follow-up endpoint.
PMID:39662163 PARTIAL Human Clinical
"VEP latency and clinical data in RENEWED should be interpreted with caution"
The follow-up study provides longer-term data but emphasizes limitations from study design and sample size.
NCT03586557 NOT_APPLICABLE UNKNOWN
Randomized study of high-dose intravenous corticosteroids with or without plasma exchange for severe acute AQP4-IgG-positive optic neuritis.
Show evidence (1 reference)
clinicaltrials:NCT03586557 SUPPORT Human Clinical
"acute aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positive optic neuritis"
The trial record documents a randomized study focused on plasma exchange in severe acute AQP4-IgG-positive optic neuritis.
NCT04762017 PHASE_II COMPLETED
ACUITY phase 2 randomized double-blind placebo-controlled study of OCS-05 added to standard-of-care corticosteroids for acute optic neuritis.
Show evidence (1 reference)
clinicaltrials:NCT04762017 SUPPORT Human Clinical
"safety and tolerability of OCS-05 compared to placebo"
The ClinicalTrials.gov record documents the acute optic neuritis OCS-05 phase 2 safety/tolerability trial.
{ }

Source YAML

click to show 
name: Optic Neuritis
creation_date: "2026-05-16T16:31:33Z"
updated_date: "2026-05-16T16:44:27Z"
category: Neurological Disorder
parents:
- Autoimmune Disorder
- Demyelinating Disease
- Eye disorder
disease_term:
  preferred_term: optic neuritis
  term:
    id: MONDO:0005885
    label: optic neuritis
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0005885
      label: optic neuritis
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: >-
      Primary MONDO disease term for the broad optic neuritis entry.
description: >-
  Optic neuritis is an inflammatory optic neuropathy in which immune-mediated
  injury of the optic nerve causes acute or subacute visual dysfunction. Modern
  classification treats optic neuritis as a heterogeneous syndrome: it can be
  isolated, multiple sclerosis-associated, MOG-IgG-associated, AQP4-IgG
  neuromyelitis optica spectrum disorder-associated, or linked to other systemic,
  infectious, or inflammatory disorders. Accurate etiologic attribution at the
  first attack is clinically important because acute treatment, relapse
  prevention, and prognosis differ across subgroups.
external_assertions:
- name: Orphanet isolated optic neuritis disease record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:499096
  url: https://www.orpha.net/en/disease/detail/499096
  description: >-
    Orphanet ORPHA:499096 is a structured record for isolated optic neuritis, a
    narrower disorder within the broader optic neuritis syndrome curated here.
    The record provides an isolated-disease definition, ICD-10/ICD-11
    cross-references, MONDO:0044688 exact mapping, and HPO phenotype
    annotations used for isolated optic neuritis features.
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0044688 | Exact"
    explanation: >-
      Orphanet maps the isolated optic neuritis record to MONDO:0044688, which
      is represented as an isolated subtype rather than the broad disease term.
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "A rare inflammatory optic neuropathy"
    explanation: >-
      Orphanet defines isolated optic neuritis as an inflammatory optic
      neuropathy.
- name: Orphanet single isolated optic neuritis subtype record
  source: Orphanet
  assertion_type: structured_subtype_record
  external_id: ORPHA:659626
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=659626
  description: >-
    Orphanet records single isolated optic neuritis as a clinical subtype of
    isolated optic neuritis and maps it exactly to MONDO:0971049.
  evidence:
  - reference: ORPHA:659626
    reference_title: Single isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0971049 | Exact"
    explanation: >-
      The Orphanet subtype record provides an exact MONDO mapping for single
      isolated optic neuritis.
- name: Orphanet relapsing isolated optic neuritis subtype record
  source: Orphanet
  assertion_type: structured_subtype_record
  external_id: ORPHA:659634
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=659634
  description: >-
    Orphanet records relapsing isolated optic neuritis as a clinical subtype of
    isolated optic neuritis and maps it exactly to MONDO:0971050.
  evidence:
  - reference: ORPHA:659634
    reference_title: Relapsing isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0971050 | Exact"
    explanation: >-
      The Orphanet subtype record provides an exact MONDO mapping for relapsing
      isolated optic neuritis.
definitions:
- name: Autoimmune optic neuritis spectrum
  definition_type: CASE_DEFINITION
  description: >-
    Autoimmune optic neuritis is a heterogeneous inflammatory optic-nerve
    syndrome spanning multiple sclerosis, NMOSD, MOGAD, isolated optic neuritis,
    and other etiologies. First-attack attribution should combine clinical red
    flags with orbital MRI, antibody assays, OCT, visual evoked potentials, and
    selected fluid biomarkers.
  criteria_sets:
  - name: Multimodal first-attack attribution
    core_clinical_characteristics:
    - preferred_term: optic neuritis
      term:
        id: HP:0100653
        label: Optic neuritis
    - preferred_term: visual loss
      term:
        id: HP:0000572
        label: Visual loss
  evidence:
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Early and accurate attribution at the first attack is clinically decisive
    explanation: >-
      The 2026 review frames autoimmune optic neuritis as a heterogeneous
      spectrum whose first-attack attribution affects treatment choice.
- name: International optic neuritis diagnostic-classification framework
  definition_type: DIAGNOSTIC_CRITERIA
  description: >-
    The 2022 international framework begins with clinical features sufficient
    for possible optic neuritis, then uses paraclinical tests including brain,
    orbital, and retinal imaging, antibody testing, and protein biomarkers to
    support definite optic neuritis and classify disease subgroups.
  evidence:
  - reference: PMID:36179757
    reference_title: Diagnosis and classification of optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      developed diagnostic criteria for optic neuritis and a classification of
      optic neuritis subgroups
    explanation: >-
      Petzold et al. provide the consensus classification framework used to
      distinguish optic neuritis subgroups.
- name: Orphanet isolated optic neuritis definition
  definition_type: OTHER
  description: >-
    Isolated optic neuritis consists of single or recurrent optic neuritis
    episodes not associated with another neurologic or systemic disease.
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      isolated episodes (either single or recurrent) of optic neuritis
    explanation: >-
      Orphanet defines the isolated subtype by single or recurrent attacks in
      the absence of another neurologic or systemic disorder.
has_subtypes:
- name: Isolated optic neuritis
  description: >-
    Optic neuritis occurring as isolated single or recurrent attacks without
    another neurologic or systemic disease explaining the presentation.
  subtype_term:
    preferred_term: isolated optic neuritis
    term:
      id: MONDO:0044688
      label: isolated optic neuritis
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      not associated with other neurological or systemic disease
    explanation: >-
      Orphanet explicitly defines isolated optic neuritis by absence of an
      associated neurologic or systemic disease.
- name: Single isolated optic neuritis
  description: >-
    A monophasic isolated optic neuritis attack without recurrent optic neuritis
    during follow-up.
  subtype_term:
    preferred_term: single isolated optic neuritis
    term:
      id: MONDO:0971049
      label: single isolated optic neuritis
  evidence:
  - reference: ORPHA:659626
    reference_title: Single isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Single isolated optic neuritis"
    explanation: >-
      Orphanet records single isolated optic neuritis as a clinical subtype of
      isolated optic neuritis.
- name: Relapsing isolated optic neuritis
  description: >-
    Recurrent isolated optic neuritis attacks without another identified
    neurologic or systemic disease driver.
  subtype_term:
    preferred_term: relapsing isolated optic neuritis
    term:
      id: MONDO:0971050
      label: relapsing isolated optic neuritis
  evidence:
  - reference: ORPHA:659634
    reference_title: Relapsing isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Relapsing isolated optic neuritis"
    explanation: >-
      Orphanet records relapsing isolated optic neuritis as a clinical subtype
      of isolated optic neuritis.
  - reference: PMID:30612145
    reference_title: Incidence and timing of recurrence of optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      monitoring for recurrence is needed even in patients with a single
      episode
    explanation: >-
      Adult follow-up data support recurrence as a clinically important course
      pattern after a first optic neuritis episode.
- name: Multiple sclerosis-associated optic neuritis
  description: >-
    Optic neuritis attributable to multiple sclerosis, often a first
    demyelinating event requiring MS-specific prognostic assessment and
    disease-modifying treatment decisions.
  evidence:
  - reference: PMID:36179757
    reference_title: Diagnosis and classification of optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      timely treatment of individuals with multiple sclerosis
    explanation: >-
      The international classification paper identifies multiple sclerosis as a
      key etiologic subgroup requiring early attribution.
- name: MOG-IgG-associated optic neuritis
  description: >-
    Optic neuritis occurring within MOG antibody-associated disease, commonly
    presenting as acute optic neuritis and often requiring MOGAD-specific
    relapse-risk assessment.
  evidence:
  - reference: PMID:36706773
    reference_title: "Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      MOGAD is typically associated with acute disseminated encephalomyelitis,
      optic neuritis, or transverse myelitis
    explanation: >-
      The international MOGAD criteria establish optic neuritis as a typical
      MOGAD phenotype.
  - reference: PMID:38783085
    reference_title: MOG antibody-associated optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MOGAD most frequently presents with optic neuritis"
    explanation: >-
      The MOG-ON review supports optic neuritis as the most frequent MOGAD
      presentation and describes bilateral involvement, disc swelling, and
      longitudinally extensive optic nerve hyperintensity as distinguishing
      features.
- name: AQP4-IgG/NMOSD-associated optic neuritis
  description: >-
    Optic neuritis caused by AQP4-IgG-positive neuromyelitis optica spectrum
    disorder. Attacks can be severe, may involve long optic-nerve segments or
    the chiasm, and should prompt NMOSD-specific relapse prevention.
  evidence:
  - reference: PMID:26092914
    reference_title: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      clinical syndromes or MRI findings related to optic nerve
    explanation: >-
      The NMOSD criteria identify optic-nerve involvement as a core clinical
      characteristic in AQP4-IgG-positive disease.
epidemiology:
- name: Colombian national incidence, 2015-2019
  description: >-
    Population-based estimate from the Colombian national health registry using
    ICD-10 optic neuritis coding.
  minimum_value: 1.56
  unit: cases per 100000 inhabitants per year
  notes: >-
    The cohort identified 2,463 new cases from 2015 to 2019; 66% of patients
    were female.
  evidence:
  - reference: PMID:38133944
    reference_title: "Colombian Ocular Inflammatory Diseases Epidemiology Study (COIDES): Optic Neuritis Incidence Between 2015-2020."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      overall 5-year incidence rate was 1.56 cases per 100,000 inhabitants per
      year
    explanation: >-
      COIDES provides a recent national population-based incidence estimate for
      optic neuritis.
- name: Afro-descendant Martinique cohort incidence, 2018-2022
  description: >-
    Retrospective cohort estimate from Martinique using the 2022 Lancet optic
    neuritis criteria after neuro-ophthalmologic evaluation.
  minimum_value: 1.61
  unit: cases per 100000 person-years
  notes: >-
    Final diagnoses included MS-associated, MOG-associated, NMOSD-associated,
    single isolated, relapsing isolated, and unclassified optic neuritis.
  evidence:
  - reference: PMID:39963868
    reference_title: "Incidence of optic neuritis among Afro-descendant, a cohort study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The overall incidence was 1.61"
    explanation: >-
      The Martinique cohort provides a population estimate in an
      Afro-descendant population and applies the 2022 criteria.
pathophysiology:
- name: Immune-mediated optic nerve inflammation
  description: >-
    Optic neuritis is driven by inflammatory injury within the optic nerve,
    producing acute or subacute visual dysfunction. The broad syndrome includes
    isolated inflammatory optic neuropathy as well as disease-specific immune
    mechanisms in MS, MOGAD, NMOSD, and systemic inflammatory disease.
  locations:
  - preferred_term: cranial nerve II
    term:
      id: UBERON:0000941
      label: cranial nerve II
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  - preferred_term: neuroinflammatory response
    term:
      id: GO:0150076
      label: neuroinflammatory response
    modifier: INCREASED
  downstream:
  - target: Optic Nerve Conduction Delay
    description: >-
      Inflammation and demyelination delay optic pathway conduction, which can
      be measured with visual evoked potentials.
  - target: Visual Dysfunction
    description: >-
      Optic nerve inflammation causes visual acuity loss, dyschromatopsia,
      visual field defects, and reduced contrast sensitivity.
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "A rare inflammatory optic neuropathy"
    explanation: >-
      The Orphanet structured record anchors the isolated form as inflammatory
      optic neuropathy.
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Autoimmune optic neuritis (ON) is a heterogeneous spectrum
    explanation: >-
      The 2026 review supports heterogeneous immune-mediated etiologies for
      optic neuritis.
- name: Inflammatory demyelinating optic neuropathy
  description: >-
    Many optic neuritis attacks are demyelinating optic neuropathies. Loss or
    dysfunction of optic nerve myelin slows visual pathway conduction and is
    reflected by prolonged visual evoked potential latency; retinal and optic
    nerve structural injury can be followed by OCT.
  locations:
  - preferred_term: cranial nerve II
    term:
      id: UBERON:0000941
      label: cranial nerve II
  cell_types:
  - preferred_term: oligodendrocyte
    term:
      id: CL:0000128
      label: oligodendrocyte
  biological_processes:
  - preferred_term: myelination
    term:
      id: GO:0042552
      label: myelination
    modifier: DECREASED
  cellular_components:
  - preferred_term: myelin sheath
    term:
      id: GO:0043209
      label: myelin sheath
    modifier: DECREASED
  downstream:
  - target: Visual Evoked Potential Latency Prolongation
    description: >-
      Demyelinating injury slows optic nerve conduction and prolongs P100 or
      full-field VEP latency.
  evidence:
  - reference: clinicaltrials:NCT01524250
    reference_title: "Recovery of Demyelinating Optic Neuritis After Treatment With Equivalent High Doses of Oral vs. Intravenous Corticosteroids: a Randomized Single Blinded Clinical Trial"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "acute demyelinating optic neuritis"
    explanation: >-
      The randomized oral-versus-intravenous corticosteroid trial record
      specifically enrolled acute demyelinating optic neuritis.
  - reference: PMID:28229892
    reference_title: "Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      measured as recovery of affected optic nerve conduction latency
    explanation: >-
      RENEW used optic nerve conduction latency recovery as a remyelination
      endpoint, linking optic neuritis to demyelinating conduction delay.
- name: MOG-IgG-mediated demyelinating optic neuritis
  description: >-
    In MOGAD-associated optic neuritis, antibodies to conformational MOG
    epitopes identify a demyelinating disease that is distinct from MS and
    AQP4-IgG NMOSD. MOG-IgG effector mechanisms include complement-dependent
    cytotoxicity, antibody-dependent cellular cytotoxicity, and T-cell supported
    CNS inflammation.
  biological_processes:
  - preferred_term: complement activation
    term:
      id: GO:0006956
      label: complement activation
    modifier: INCREASED
  - preferred_term: T cell mediated immunity
    term:
      id: GO:0002456
      label: T cell mediated immunity
    modifier: INCREASED
  downstream:
  - target: Inflammatory Demyelinating Optic Neuropathy
    description: >-
      MOG-IgG effector mechanisms converge on oligodendrocyte/myelin injury in
      optic neuritis attacks.
  evidence:
  - reference: PMID:36706773
    reference_title: "Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Serum antibodies directed against myelin oligodendrocyte glycoprotein
    explanation: >-
      International criteria establish serum MOG-IgG as the defining biomarker
      for MOGAD, a common optic neuritis etiology.
  - reference: PMID:40088708
    reference_title: "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Insights into pathogenesis and biomarkers of prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      MOG-IgG-mediated demyelination occurs via complement-dependent
      cytotoxicity
    explanation: >-
      The review describes antibody effector mechanisms relevant to MOGAD optic
      neuritis.
- name: AQP4-IgG astrocytopathic optic neuritis
  description: >-
    In AQP4-IgG-positive NMOSD, optic neuritis reflects astrocyte-targeted
    autoimmunity with complement-mediated injury and secondary demyelination.
    This mechanism differs from primary MS-type demyelination and from MOGAD.
  genes:
  - preferred_term: AQP4
    term:
      id: hgnc:637
      label: AQP4
  cell_types:
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  biological_processes:
  - preferred_term: complement activation, classical pathway
    term:
      id: GO:0006958
      label: complement activation, classical pathway
    modifier: INCREASED
  downstream:
  - target: Secondary Demyelination and Neuronal Injury
    description: >-
      Complement-mediated astrocyte injury propagates demyelinating and axonal
      damage in optic pathways.
  evidence:
  - reference: PMID:26092914
    reference_title: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      associated with serum aquaporin-4 immunoglobulin G antibodies
    explanation: >-
      The NMOSD consensus criteria establish AQP4-IgG as the defining
      serologic marker for the AQP4-positive optic neuritis subgroup.
phenotypes:
- name: Optic Neuritis
  description: >-
    Inflammation of the optic nerve with acute or subacute visual symptoms.
  category: Ophthalmologic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: optic neuritis
    term:
      id: HP:0100653
      label: Optic neuritis
  evidence:
  - reference: PMID:36179757
    reference_title: Diagnosis and classification of optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "diagnostic criteria for optic neuritis"
    explanation: >-
      Optic neuritis is the defining phenotype and the target of the
      diagnostic classification framework.
- name: Bilateral Optic Neuritis
  description: >-
    Bilateral optic nerve involvement is a distinguishing clinical pattern in
    MOG-IgG-associated optic neuritis and may also occur in some NMOSD and
    pediatric presentations. HPO lacks a specific bilateral optic neuritis term,
    so the base optic neuritis phenotype is used with a bilateral preferred
    term.
  category: Ophthalmologic
  subtype: MOG-IgG-associated optic neuritis
  frequency: FREQUENT
  phenotype_term:
    preferred_term: bilateral optic neuritis
    term:
      id: HP:0100653
      label: Optic neuritis
  evidence:
  - reference: PMID:38783085
    reference_title: MOG antibody-associated optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bilateral involvement, disc swelling clinically and radiologically
    explanation: >-
      The 2024 MOG-ON review identifies bilateral involvement and disc swelling
      as characteristic features that help distinguish MOG-associated optic
      neuritis from other etiologies.
- name: Visual Loss
  description: >-
    Acute or subacute visual loss is a key presenting manifestation, ranging
    from blurred vision to severe loss of acuity depending on etiology and
    attack severity.
  category: Ophthalmologic
  frequency: COMMON
  phenotype_term:
    preferred_term: visual loss
    term:
      id: HP:0000572
      label: Visual loss
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "subacute unilateral loss of vision"
    explanation: >-
      Orphanet lists subacute unilateral visual loss as a typical presentation
      of isolated optic neuritis.
- name: Eye Movement-Induced Pain
  description: >-
    Periocular pain, often worsened by eye movement, is a common symptom and may
    precede visual symptoms.
  category: Ophthalmologic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Eye movement-induced pain
    term:
      id: HP:0030857
      label: Eye movement-induced pain
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "pain on eye movement"
    explanation: >-
      Orphanet annotates eye movement-induced pain as very frequent in isolated
      optic neuritis.
- name: Ocular Pain
  description: >-
    Ocular or periocular pain is a frequent presenting symptom.
  category: Ophthalmologic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Ocular pain
    term:
      id: HP:0200026
      label: Ocular pain
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "periocular pain"
    explanation: >-
      Orphanet annotates ocular pain as very frequent in isolated optic
      neuritis.
- name: Dyschromatopsia
  description: >-
    Abnormal color vision is common and can be disproportionate to visual acuity
    loss.
  category: Ophthalmologic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Dyschromatopsia
    term:
      id: HP:0007641
      label: Dyschromatopsia
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "abnormal color vision"
    explanation: >-
      Orphanet annotates dyschromatopsia as very frequent in isolated optic
      neuritis.
- name: Visual Field Defect
  description: >-
    Visual field loss is a common objective manifestation of optic nerve
    dysfunction.
  category: Ophthalmologic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Visual field defect
    term:
      id: HP:0001123
      label: Visual field defect
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Visual field defect"
    explanation: >-
      Orphanet annotates visual field defect as very frequent in isolated optic
      neuritis.
- name: Central Scotoma
  description: >-
    Central visual field loss may occur because optic neuritis often affects
    fibers serving central vision.
  category: Ophthalmologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Central scotoma
    term:
      id: HP:0000603
      label: Central scotoma
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Central scotoma"
    explanation: >-
      Orphanet annotates central scotoma as frequent in isolated optic
      neuritis.
- name: Reduced Contrast Sensitivity
  description: >-
    Reduced contrast sensitivity can persist even when high-contrast visual
    acuity improves.
  category: Ophthalmologic
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Reduced contrast sensitivity
    term:
      id: HP:0032036
      label: Reduced contrast sensitivity
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "reduced contrast sensitivity"
    explanation: >-
      Orphanet annotates reduced contrast sensitivity as very frequent in
      isolated optic neuritis.
- name: Marcus Gunn Pupil
  description: >-
    A relative afferent pupillary defect can occur with unilateral or asymmetric
    optic nerve dysfunction.
  category: Ophthalmologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Marcus Gunn pupil
    term:
      id: HP:0200057
      label: Marcus Gunn pupil
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "relative afferent pupillary defect"
    explanation: >-
      Orphanet lists relative afferent pupillary defect and annotates Marcus
      Gunn pupil as frequent.
- name: Optic Disc Swelling
  description: >-
    Optic disc edema or papillitis may be present, particularly in some
    pediatric, MOG-associated, and isolated optic neuritis presentations.
  category: Ophthalmologic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Optic disc edema
    term:
      id: HP:0012795
      label: Abnormal optic disc morphology
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "optic disc appears swollen"
    explanation: >-
      Orphanet lists swollen optic disc as a frequent isolated optic neuritis
      feature; HP:0012795 is used as the closest HPO parent because papilledema
      specifically denotes optic disc swelling from raised intracranial
      pressure.
- name: Photopsia
  description: >-
    Light flashes with eye movement can occur in a minority of patients.
  category: Ophthalmologic
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Photopsia
    term:
      id: HP:0030786
      label: Photopsia
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "light flashes on eye movement"
    explanation: >-
      Orphanet annotates photopsia as occasional in isolated optic neuritis.
- name: Abnormal Visual Evoked Potentials
  description: >-
    Visual evoked potential latency can be prolonged by demyelinating optic
    nerve injury and can be used as an objective functional measure.
  category: Electrophysiologic
  phenotype_term:
    preferred_term: Abnormality of visual evoked potentials
    term:
      id: HP:0000649
      label: Abnormality of visual evoked potentials
  evidence:
  - reference: PMID:29507942
    reference_title: "Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "P100 component of the visual evoked potential"
    explanation: >-
      The randomized corticosteroid trial used VEP P100 latency recovery as a
      primary optic nerve function outcome.
biochemical:
- name: MOG-IgG seropositivity
  presence: PRESENT
  context: >-
    Serum MOG-IgG identifies MOGAD-associated optic neuritis and should be
    interpreted with assay quality, titer, and phenotype in mind.
  evidence:
  - reference: PMID:36706773
    reference_title: "Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "presence of MOG-IgG is a core criterion"
    explanation: >-
      International MOGAD criteria define MOG-IgG as a core diagnostic
      criterion for MOGAD-associated optic neuritis.
- name: AQP4-IgG seropositivity
  presence: PRESENT
  context: >-
    Serum AQP4-IgG identifies NMOSD-associated optic neuritis and strongly
    changes relapse-prevention and acute-attack management.
  evidence:
  - reference: PMID:26092914
    reference_title: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "NMOSD with or without AQP4-IgG"
    explanation: >-
      The NMOSD consensus framework stratifies disease by AQP4-IgG serostatus.
- name: Serum neurofilament light chain and serum GFAP
  presence: INCREASED
  context: >-
    Serum neurofilament light chain and serum glial fibrillary acidic protein
    are emerging injury biomarkers that may help refine risk estimates,
    particularly in seronegative or diagnostically gray-zone optic neuritis.
  evidence:
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      may refine risk estimates, especially in seronegative cases
    explanation: >-
      The 2026 review identifies sNfL and sGFAP as emerging adjunct biomarkers
      for risk estimation in autoimmune optic neuritis.
diagnosis:
- name: Multimodal optic neuritis classification workup
  description: >-
    Diagnostic evaluation should establish optic neuritis and then attribute the
    attack to the correct subgroup using clinical pattern, brain/orbital/retinal
    imaging, antibody testing, VEP, and selected protein biomarkers.
  results: >-
    Supports classification into isolated, MS-associated, MOGAD-associated,
    NMOSD-associated, systemic inflammatory, infectious, or unclassified optic
    neuritis.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: MAXO:0000003
      label: diagnostic procedure
  evidence:
  - reference: PMID:36179757
    reference_title: Diagnosis and classification of optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      brain, orbital, and retinal imaging, together with antibody and other
      protein biomarker data
    explanation: >-
      The international framework supports a multimodal diagnostic process for
      definite optic neuritis and subgroup classification.
- name: Orbital and brain MRI
  description: >-
    MRI documents optic nerve enhancement or T2 signal abnormality, screens for
    MS-type brain lesions, and helps identify NMOSD or MOGAD red flags such as
    long optic-nerve involvement, chiasmal extension, or associated myelitis.
  results: >-
    MRI supports diagnosis and etiologic classification when interpreted with
    clinical pattern and serology.
  diagnosis_term:
    preferred_term: magnetic resonance imaging procedure
    term:
      id: MAXO:0000424
      label: magnetic resonance imaging procedure
  evidence:
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      standardized diagnostic pathways integrating orbital magnetic resonance
      imaging
    explanation: >-
      The 2026 review identifies orbital MRI as a key component of standardized
      diagnostic pathways.
- name: Optical coherence tomography
  description: >-
    OCT measures retinal nerve fiber layer and ganglion cell complex injury,
    helping quantify structural damage and follow recovery or atrophy after an
    attack.
  results: >-
    OCT provides retinal structural markers that complement MRI, VEP, and
    serologic testing.
  diagnosis_term:
    preferred_term: optical coherence tomography
    term:
      id: MAXO:0000969
      label: optical coherence tomography
  evidence:
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "antibody assays, OCT, and visual evoked potentials"
    explanation: >-
      The 2026 review lists OCT among tools needed for standardized autoimmune
      optic neuritis diagnosis.
  - reference: PMID:36810323
    reference_title: Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Results support the validation of the IED metrics
    explanation: >-
      This multicenter AQP4+ NMOSD study validates OCT intereye-difference
      metrics for optic neuritis in an antibody-defined subgroup.
  - reference: PMID:39231384
    reference_title: Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      diagnostic accuracy of OCT-based IED metrics for ON was high
    explanation: >-
      This multicenter MOG-ON study validates OCT intereye-difference metrics,
      especially macular ganglion cell and inner plexiform layer percentage
      difference.
- name: Visual evoked potential procedure
  description: >-
    Visual evoked potentials assess optic pathway conduction delay and can
    provide functional evidence of demyelinating optic nerve injury.
  results: >-
    Prolonged VEP latency supports optic nerve conduction slowing and can be
    tracked during recovery.
  diagnosis_term:
    preferred_term: visual evoked potential procedure
    term:
      id: MAXO:0035097
      label: visual evoked potential procedure
  evidence:
  - reference: PMID:29507942
    reference_title: "Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "recovery of the latency of the P100 component"
    explanation: >-
      VEP latency recovery was used as a functional optic nerve outcome in a
      randomized optic neuritis treatment trial.
- name: AQP4-IgG and MOG-IgG antibody testing
  description: >-
    Serum antibody testing is central for distinguishing MOGAD-associated and
    AQP4-IgG NMOSD-associated optic neuritis from MS-associated, isolated, and
    other inflammatory optic neuritis.
  results: >-
    Positive MOG-IgG or AQP4-IgG redirects the diagnosis to an antibody-defined
    demyelinating disease subgroup.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: MAXO:0000003
      label: diagnostic procedure
  evidence:
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "high-quality antibody assays"
    explanation: >-
      The 2026 review emphasizes high-quality antibody assays in standardized
      diagnostic pathways.
differential_diagnoses:
- name: Nonarteritic anterior ischemic optic neuropathy
  description: >-
    Ischemic optic neuropathy is a common optic neuritis mimic in referred
    patients and should be considered when age, vascular risk factors, disc
    appearance, pain pattern, and imaging are atypical for inflammatory optic
    neuritis.
  distinguishing_features:
  - Often painless sudden vision loss rather than subacute painful inflammatory visual loss.
  - Optic disc findings and vascular risk profile may favor ischemic neuropathy.
  evidence:
  - reference: PMID:29222573
    reference_title: Incidence and Causes of Overdiagnosis of Optic Neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      other optic neuropathies, particularly nonarteritic anterior ischemic
      optic neuropathy
    explanation: >-
      The overdiagnosis study identifies nonarteritic anterior ischemic optic
      neuropathy as a frequent alternative diagnosis.
- name: Headache, ocular pain, and functional visual loss mimics
  description: >-
    Headache syndromes, eye pain without optic nerve inflammation, and
    functional visual loss can be misclassified as optic neuritis when isolated
    history items are overweighted.
  distinguishing_features:
  - Normal objective afferent visual pathway findings argue against optic neuritis.
  - A single symptom such as eye pain should not substitute for optic nerve evidence.
  evidence:
  - reference: PMID:29222573
    reference_title: Incidence and Causes of Overdiagnosis of Optic Neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      headache and eye pain, functional visual loss
    explanation: >-
      These were among the most common alternative diagnoses in patients
      referred with suspected acute optic neuritis.
- name: Infectious and systemic inflammatory optic neuropathies
  description: >-
    Infectious optic neuropathies and systemic inflammatory diseases such as
    sarcoidosis, SLE, Behcet disease, and vasculitis can produce optic neuritis
    or optic neuropathy and require targeted evaluation when clinical context or
    imaging is atypical for MS, MOGAD, NMOSD, or isolated optic neuritis.
  distinguishing_features:
  - Systemic symptoms, uveitis, granulomatous disease, vascular inflammation, or infectious exposure can redirect evaluation.
  - Etiology-specific treatment may be required beyond acute corticosteroids.
  evidence:
  - reference: PMID:41688447
    reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "and other etiologies"
    explanation: >-
      The 2026 review frames autoimmune optic neuritis as a spectrum that
      includes other etiologies beyond MS, NMOSD, and MOGAD.
progression:
- phase: Acute attack
  subtype: Isolated optic neuritis
  notes: >-
    Visual loss typically evolves subacutely over days to two weeks and is often
    accompanied by periocular pain, eye movement pain, dyschromatopsia, and
    reduced contrast sensitivity.
  duration_days: "1-14"
  evidence:
  - reference: ORPHA:499096
    reference_title: Isolated optic neuritis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      progressing over several days to two weeks
    explanation: >-
      Orphanet provides the typical isolated optic neuritis time course.
- phase: Recurrence risk after first optic neuritis episode
  notes: >-
    Recurrence risk continues over long-term follow-up, especially in patients
    with early relapse or AQP4-IgG positivity.
  evidence:
  - reference: PMID:30612145
    reference_title: Incidence and timing of recurrence of optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      recurrence in either eye was 26% at 1 year
    explanation: >-
      The adult follow-up cohort quantified recurrence after first optic
      neuritis and supports long-term monitoring.
- phase: Multiple sclerosis risk stratification after undifferentiated optic neuritis
  notes: >-
    At first presentation with undifferentiated optic neuritis, demographic
    variables plus an MS genetic risk score can improve prediction of later
    multiple sclerosis diagnosis.
  evidence:
  - reference: PMID:38418465
    reference_title: Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold
    explanation: >-
      This UK Biobank, Geisinger, and FinnGen analysis supports genetic-risk
      stratification as an emerging prognostic tool after first optic neuritis.
- phase: Pediatric presentation
  notes: >-
    Children, especially those younger than 10 years, more often have bilateral
    optic neuritis; pediatric workup must consider ADEM, MOGAD, NMOSD, MS,
    infection, and post-infectious or post-vaccination contexts.
  evidence:
  - reference: PMID:27572862
    reference_title: Pediatric optic neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      younger children (<10 years of age) are more likely to present with
      bilateral ON
    explanation: >-
      The pediatric review supports age-dependent differences in bilateral
      presentation.
  - reference: PMID:28941527
    reference_title: Pediatric Optic Neuritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      higher rate of bilaterality, poor visual acuity on presentation, and
      papillitis
    explanation: >-
      This pediatric review summarizes major clinical differences from adult
      optic neuritis.
treatments:
- name: Acute high-dose corticosteroids
  description: >-
    High-dose corticosteroids, usually intravenous methylprednisolone or a
    bioequivalent high-dose oral regimen, accelerate recovery in acute optic
    neuritis. Low-dose oral prednisone alone, as used in the original ONTT, is
    not equivalent and increased new optic neuritis episodes.
  treatment_term:
    preferred_term: systemic corticosteroid therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  target_mechanisms:
  - target: Immune-mediated optic nerve inflammation
    treatment_effect: INHIBITS
    description: >-
      High-dose corticosteroids suppress acute inflammatory optic nerve injury
      and speed visual recovery.
  evidence:
  - reference: PMID:1734247
    reference_title: "A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Visual function recovered faster in the group receiving intravenous
      methylprednisolone
    explanation: >-
      ONTT supports high-dose intravenous methylprednisolone for faster visual
      recovery in acute optic neuritis.
  - reference: PMID:29507942
    reference_title: "Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      bioequivalent doses of oral corticosteroids may be used as an alternative
      to IV corticosteroids
    explanation: >-
      This randomized trial supports bioequivalent high-dose oral
      corticosteroids as an alternative route to high-dose IV therapy.
  - reference: PMID:1734247
    reference_title: "A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oral prednisone alone, as prescribed in this study, is an ineffective
      treatment
    explanation: >-
      The ONTT finding distinguishes high-dose steroid treatment from low-dose
      oral prednisone monotherapy.
- name: Plasma exchange escalation for severe or steroid-refractory optic neuritis
  description: >-
    Therapeutic plasma exchange is considered for severe or steroid-refractory
    optic neuritis, especially in NMOSD/AQP4-associated attacks. Evidence is
    strongest in observational NMO/NMOSD relapse cohorts, while aggregate data
    specific to acute NMO/NMOSD optic neuritis remain limited.
  treatment_term:
    preferred_term: plasmapheresis
    term:
      id: NCIT:C15304
      label: Plasmapheresis
  target_mechanisms:
  - target: AQP4-IgG/NMOSD-associated optic neuritis
    treatment_effect: INHIBITS
    description: >-
      Plasma exchange removes circulating pathogenic antibodies and complement
      mediators during severe antibody-associated attacks.
  evidence:
  - reference: PMID:25921047
    reference_title: "Treatment of acute relapses in neuromyelitis optica: Steroids alone versus steroids plus plasma exchange."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      PLEX+IVMP are more likely to improve EDSS after NMO relapses
    explanation: >-
      This NMO/NMOSD relapse cohort supports adding plasma exchange to
      high-dose steroids, including relapses involving the optic nerves.
  - reference: PMID:36822570
    reference_title: "Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most ON attacks improved with PLEX"
    explanation: >-
      The 395-attack international cohort supports PLEX as a clinically useful
      escalation therapy for severe optic neuritis and identifies delayed PLEX
      as a poor-outcome predictor.
  - reference: PMID:15452303
    reference_title: "Plasma exchange for severe optic neuritis: treatment of 10 patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      PE may be beneficial as an escalating treatment
    explanation: >-
      This severe optic neuritis case series supports plasma exchange as an
      escalation option when high-dose steroids are insufficient.
  - reference: PMID:37387119
    reference_title: "Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      inadequate data to determine whether PLEX effectively treats acute ON
    explanation: >-
      The systematic review supports clinical plausibility but cautions that
      definitive evidence for acute NMO/NMOSD optic neuritis remains limited.
- name: Maintenance intravenous immunoglobulin for relapsing MOGAD-associated optic neuritis
  description: >-
    Maintenance IVIG is used as a relapse-prevention option in relapsing MOGAD,
    including patients whose MOGAD phenotype includes optic neuritis. Evidence is
    retrospective and subtype-specific rather than a general treatment for all
    optic neuritis.
  treatment_term:
    preferred_term: intravenous immunoglobulin therapy
    term:
      id: MAXO:0001480
      label: immunoglobulin infusion therapy
  target_mechanisms:
  - target: MOG-IgG-mediated demyelinating optic neuritis
    treatment_effect: INHIBITS
    description: >-
      IVIG is used to reduce relapsing MOG-IgG-associated inflammatory
      demyelinating attacks.
  evidence:
  - reference: PMID:35377395
    reference_title: Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      maintenance IVIG was associated with a reduction in disease relapse
    explanation: >-
      This international adult MOGAD cohort supports maintenance IVIG as a
      relapse-prevention strategy relevant to relapsing MOG-associated optic
      neuritis.
- name: Eculizumab relapse prevention for AQP4-IgG/NMOSD-associated optic neuritis
  description: >-
    Complement C5 blockade with eculizumab reduces relapse risk in
    AQP4-IgG-positive NMOSD; this is relevant to optic neuritis when optic nerve
    attacks occur as part of AQP4-IgG/NMOSD-associated disease.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: eculizumab
      term:
        id: NCIT:C48386
        label: Eculizumab
  target_mechanisms:
  - target: AQP4-IgG astrocytopathic optic neuritis
    treatment_effect: INHIBITS
    description: >-
      C5 blockade reduces terminal complement-mediated astrocyte injury in
      AQP4-IgG-positive NMOSD.
  evidence:
  - reference: PMID:31050279
    reference_title: Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab
      group and 20 of 47 (43%) in the placebo group
    explanation: >-
      The PREVENT trial supports eculizumab for relapse prevention in
      AQP4-IgG-positive NMOSD, including prevention of recurrent optic neuritis
      attacks in that subtype context.
clinical_trials:
- name: NCT00000146
  phase: PHASE_III
  status: UNKNOWN
  description: >-
    Historic Optic Neuritis Treatment Trial evaluating corticosteroid treatment,
    natural history, and MS risk after optic neuritis.
  evidence:
  - reference: clinicaltrials:NCT00000146
    reference_title: Optic Neuritis Treatment Trial (ONTT)
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      To assess the beneficial and adverse effects of corticosteroid treatment
      for optic neuritis.
    explanation: >-
      The ClinicalTrials.gov record documents the ONTT corticosteroid treatment
      and natural-history objectives.
  - reference: PMID:1734247
    reference_title: "A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      randomly assigned 457 patients with acute optic neuritis
    explanation: >-
      The NEJM publication reports the pivotal ONTT corticosteroid trial.
- name: NCT01524250
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomized single-blind trial comparing bioequivalent high-dose oral versus
    intravenous corticosteroids for acute demyelinating optic neuritis.
  evidence:
  - reference: clinicaltrials:NCT01524250
    reference_title: "Recovery of Demyelinating Optic Neuritis After Treatment With Equivalent High Doses of Oral vs. Intravenous Corticosteroids: a Randomized Single Blinded Clinical Trial"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      randomized to receive equivalent doses of either intravenous (IV) or oral
      corticosteroid treatment
    explanation: >-
      The trial record documents the randomized oral-versus-IV corticosteroid
      comparison.
  - reference: PMID:29507942
    reference_title: "Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      no significant difference between groups
    explanation: >-
      The published trial found no significant recovery difference between
      bioequivalent oral and IV high-dose corticosteroids.
- name: NCT01721161
  phase: PHASE_II
  status: COMPLETED
  description: >-
    RENEW randomized placebo-controlled phase 2 trial of BIIB033/opicinumab
    after first unilateral acute optic neuritis, evaluating remyelination by
    visual evoked potential latency recovery.
  evidence:
  - reference: clinicaltrials:NCT01721161
    reference_title: "A Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With First Episode of Acute Optic Neuritis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      evaluate the efficacy of BIIB033 in subjects with their first episode of
      unilateral acute optic neuritis
    explanation: >-
      The trial record documents the RENEW acute optic neuritis study.
  - reference: PMID:28229892
    reference_title: "Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Remyelination did not differ significantly between the opicinumab and
      placebo groups
    explanation: >-
      RENEW was mechanistically important but did not meet the primary
      intention-to-treat remyelination endpoint.
- name: NCT02657915
  phase: PHASE_II
  status: COMPLETED
  description: >-
    RENEWED follow-up study assessing long-term electrophysiologic and clinical
    outcomes in participants from the RENEW opicinumab acute optic neuritis
    trial.
  evidence:
  - reference: clinicaltrials:NCT02657915
    reference_title: "A Multicenter, Follow-Up Study to Assess Long-Term Electrophysiologic and Clinical Outcomes in Subjects Previously Enrolled in Study 215ON201"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      assess full-field visual evoked potential (FF-VEP) latency
    explanation: >-
      The trial record documents the long-term VEP follow-up endpoint.
  - reference: PMID:39662163
    reference_title: "RENEWED: A follow-up study of the opicinumab phase 2 RENEW study in participants with acute optic neuritis."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      VEP latency and clinical data in RENEWED should be interpreted with
      caution
    explanation: >-
      The follow-up study provides longer-term data but emphasizes limitations
      from study design and sample size.
- name: NCT03586557
  phase: NOT_APPLICABLE
  status: UNKNOWN
  description: >-
    Randomized study of high-dose intravenous corticosteroids with or without
    plasma exchange for severe acute AQP4-IgG-positive optic neuritis.
  evidence:
  - reference: clinicaltrials:NCT03586557
    reference_title: Effectiveness of Plasma Exchange in Treating With Severe Acute AQP4-Ab Positive Optic Neuritis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      acute aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positive optic
      neuritis
    explanation: >-
      The trial record documents a randomized study focused on plasma exchange
      in severe acute AQP4-IgG-positive optic neuritis.
- name: NCT04762017
  phase: PHASE_II
  status: COMPLETED
  description: >-
    ACUITY phase 2 randomized double-blind placebo-controlled study of OCS-05
    added to standard-of-care corticosteroids for acute optic neuritis.
  evidence:
  - reference: clinicaltrials:NCT04762017
    reference_title: "A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of OCS-05 in Patients With Acute Optic Neuritis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      safety and tolerability of OCS-05 compared to placebo
    explanation: >-
      The ClinicalTrials.gov record documents the acute optic neuritis OCS-05
      phase 2 safety/tolerability trial.
datasets: []
references:
- reference: ORPHA:499096
  title: Isolated optic neuritis
  findings:
  - statement: Orphanet defines isolated optic neuritis and provides phenotype annotations.
    supporting_text: A rare inflammatory optic neuropathy
    evidence:
    - reference: ORPHA:499096
      reference_title: Isolated optic neuritis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "A rare inflammatory optic neuropathy"
      explanation: >-
        Supports the isolated optic neuritis subtype and its phenotype
        annotations.
- reference: ORPHA:659626
  title: Single isolated optic neuritis
  findings:
  - statement: Orphanet maps single isolated optic neuritis to MONDO:0971049.
    supporting_text: "MONDO:0971049 | Exact"
    evidence:
    - reference: ORPHA:659626
      reference_title: Single isolated optic neuritis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "MONDO:0971049 | Exact"
      explanation: >-
        Supports the single isolated optic neuritis subtype term.
- reference: ORPHA:659634
  title: Relapsing isolated optic neuritis
  findings:
  - statement: Orphanet maps relapsing isolated optic neuritis to MONDO:0971050.
    supporting_text: "MONDO:0971050 | Exact"
    evidence:
    - reference: ORPHA:659634
      reference_title: Relapsing isolated optic neuritis
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "MONDO:0971050 | Exact"
      explanation: >-
        Supports the relapsing isolated optic neuritis subtype term.
- reference: PMID:41688447
  title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
  findings:
  - statement: Autoimmune optic neuritis is heterogeneous and needs standardized first-attack attribution.
    supporting_text: >-
      Early and accurate attribution at the first attack is clinically decisive
    evidence:
    - reference: PMID:41688447
      reference_title: An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Early and accurate attribution at the first attack is clinically
        decisive
      explanation: >-
        Supports the diagnostic framing and the need for multimodal workup.
- reference: PMID:36179757
  title: Diagnosis and classification of optic neuritis.
  findings:
  - statement: International consensus criteria classify optic neuritis subgroups using clinical and paraclinical data.
    supporting_text: >-
      diagnostic criteria for optic neuritis and a classification of optic
      neuritis subgroups
    evidence:
    - reference: PMID:36179757
      reference_title: Diagnosis and classification of optic neuritis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        diagnostic criteria for optic neuritis and a classification of optic
        neuritis subgroups
      explanation: >-
        Supports use of the Petzold et al. framework for subgroup curation.
- reference: PMID:29222573
  title: Incidence and Causes of Overdiagnosis of Optic Neuritis.
  findings:
  - statement: Overdiagnosis is common in referral cohorts, especially due to mimics.
    supporting_text: >-
      nearly 60% ... of patients referred for optic neuritis have an alternative
      diagnosis
    evidence:
    - reference: PMID:29222573
      reference_title: Incidence and Causes of Overdiagnosis of Optic Neuritis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        patients referred for optic neuritis have an alternative diagnosis
      explanation: >-
        Supports the differential-diagnosis section and diagnostic caution.
- reference: PMID:1734247
  title: "A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group."
  findings:
  - statement: High-dose IV methylprednisolone accelerates visual recovery, while low-dose oral prednisone alone is not effective.
    supporting_text: Visual function recovered faster
    evidence:
    - reference: PMID:1734247
      reference_title: "A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Visual function recovered faster"
      explanation: >-
        Supports acute high-dose corticosteroid therapy.
- reference: PMID:29507942
  title: "Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial."
  findings:
  - statement: Bioequivalent high-dose oral corticosteroids can be an alternative to IV corticosteroids.
    supporting_text: >-
      bioequivalent doses of oral corticosteroids may be used as an alternative
    evidence:
    - reference: PMID:29507942
      reference_title: "Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        bioequivalent doses of oral corticosteroids may be used as an
        alternative
      explanation: >-
        Supports high-dose oral corticosteroid equivalence to IV dosing.
- reference: PMID:37387119
  title: "Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review."
  findings:
  - statement: Evidence for plasma exchange in acute NMO/NMOSD optic neuritis remains limited.
    supporting_text: inadequate data to determine whether PLEX effectively treats acute ON
    evidence:
    - reference: PMID:37387119
      reference_title: "Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review."
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        inadequate data to determine whether PLEX effectively treats acute ON
      explanation: >-
        Captures the treatment-evidence limitation for plasma exchange.
- reference: PMID:39963868
  title: "Incidence of optic neuritis among Afro-descendant, a cohort study."
  findings:
  - statement: A 2018-2022 Martinique cohort estimated optic neuritis incidence and etiologic distribution.
    supporting_text: The overall incidence was 1.61
    evidence:
    - reference: PMID:39963868
      reference_title: "Incidence of optic neuritis among Afro-descendant, a cohort study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The overall incidence was 1.61"
      explanation: >-
        Supports epidemiology and subtype distribution.
- reference: PMID:38783085
  title: MOG antibody-associated optic neuritis.
  findings:
  - statement: MOGAD most frequently presents with optic neuritis and has characteristic clinical and radiologic features.
    supporting_text: MOGAD most frequently presents with optic neuritis
    evidence:
    - reference: PMID:38783085
      reference_title: MOG antibody-associated optic neuritis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "MOGAD most frequently presents with optic neuritis"
      explanation: >-
        Supports MOG-IgG-associated optic neuritis as a major antibody-defined
        subtype.
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: PMID:35377395
  title: Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.
  findings:
  - statement: Maintenance IVIG was associated with reduced relapse activity in adult MOGAD.
    supporting_text: >-
      maintenance IVIG was associated with a reduction in disease relapse
    evidence:
    - reference: PMID:35377395
      reference_title: Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        maintenance IVIG was associated with a reduction in disease relapse
      explanation: >-
        Supports maintenance IVIG as relapse prevention for relapsing
        MOG-IgG-associated disease, including MOG-associated optic neuritis.
- reference: PMID:36810323
  title: Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders
  findings:
  - statement: OCT intereye-difference metrics are validated diagnostic parameters in AQP4-positive NMOSD optic neuritis.
    supporting_text: Results support the validation of the IED metrics
    evidence:
    - reference: PMID:36810323
      reference_title: Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Results support the validation of the IED metrics
      explanation: >-
        Supports OCT intereye-difference metrics as diagnostic support in
        AQP4-positive NMOSD-associated optic neuritis.
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: PMID:39231384
  title: Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.
  findings:
  - statement: OCT intereye-difference metrics have high diagnostic accuracy for MOG-IgG-associated optic neuritis.
    supporting_text: diagnostic accuracy of OCT-based IED metrics for ON was high
    evidence:
    - reference: PMID:39231384
      reference_title: Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        diagnostic accuracy of OCT-based IED metrics for ON was high
      explanation: >-
        Supports OCT intereye-difference metrics as diagnostic support in
        MOG-IgG-associated optic neuritis.
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: PMID:38418465
  title: Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis.
  findings:
  - statement: MS genetic risk score plus demographics improves MS prediction after undifferentiated optic neuritis.
    supporting_text: one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold
    evidence:
    - reference: PMID:38418465
      reference_title: Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold
      explanation: >-
        Supports genetic-risk-score stratification as an emerging prognostic
        approach after first optic neuritis.
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: PMID:36822570
  title: "Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks."
  findings:
  - statement: A large international cohort found most severe optic neuritis attacks improved with PLEX.
    supporting_text: Most ON attacks improved with PLEX
    evidence:
    - reference: PMID:36822570
      reference_title: "Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Most ON attacks improved with PLEX"
      explanation: >-
        Supports plasma exchange as escalation therapy in severe optic neuritis
        while preserving timing and severity as prognostic factors.
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: PMID:31050279
  title: Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.
  findings:
  - statement: Eculizumab substantially reduced relapse risk in AQP4-IgG-positive NMOSD.
    supporting_text: >-
      Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab
      group and 20 of 47 (43%) in the placebo group
    evidence:
    - reference: PMID:31050279
      reference_title: Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab
        group and 20 of 47 (43%) in the placebo group
      explanation: >-
        Supports complement C5 blockade as relapse prevention for
        AQP4-IgG-positive NMOSD, including the NMOSD-associated optic neuritis
        subtype context.
- reference: DOI:10.1016/j.ajo.2023.02.013
  title: "Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks"
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.1038/s41433-024-03108-y
  title: MOG antibody-associated optic neuritis
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.1038/s41467-024-44917-9
  title: Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.1136/jnnp-2022-330608
  title: Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.1177/13524585231224683
  title: Prevalence of neuromyelitis optica spectrum disorder in the United States
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.1212/nxi.0000000000200214
  title: Acute Optic Neuropathy in Older Adults
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.1212/nxi.0000000000200291
  title: Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.3390/ijms242115986
  title: "Beyond Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies: Alternative Causes of Optic Neuritis"
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
- reference: DOI:10.7759/cureus.56094
  title: "A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis"
  findings: []
  found_in:
  - Optic_Neuritis-deep-research-falcon.md
📚

References & Deep Research

References

26
ORPHA:499096
Isolated optic neuritis
1 finding
Orphanet defines isolated optic neuritis and provides phenotype annotations.
"A rare inflammatory optic neuropathy"
Show evidence (1 reference)
ORPHA:499096 SUPPORT Other
"A rare inflammatory optic neuropathy"
Supports the isolated optic neuritis subtype and its phenotype annotations.
ORPHA:659626
Single isolated optic neuritis
1 finding
Orphanet maps single isolated optic neuritis to MONDO:0971049.
"MONDO:0971049 | Exact"
Show evidence (1 reference)
ORPHA:659626 SUPPORT Other
"MONDO:0971049 | Exact"
Supports the single isolated optic neuritis subtype term.
ORPHA:659634
Relapsing isolated optic neuritis
1 finding
Orphanet maps relapsing isolated optic neuritis to MONDO:0971050.
"MONDO:0971050 | Exact"
Show evidence (1 reference)
ORPHA:659634 SUPPORT Other
"MONDO:0971050 | Exact"
Supports the relapsing isolated optic neuritis subtype term.
PMID:41688447
An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis.
1 finding
Autoimmune optic neuritis is heterogeneous and needs standardized first-attack attribution.
"Early and accurate attribution at the first attack is clinically decisive"
Show evidence (1 reference)
PMID:41688447 SUPPORT Human Clinical
"Early and accurate attribution at the first attack is clinically decisive"
Supports the diagnostic framing and the need for multimodal workup.
PMID:36179757
Diagnosis and classification of optic neuritis.
1 finding
International consensus criteria classify optic neuritis subgroups using clinical and paraclinical data.
"diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups"
Show evidence (1 reference)
PMID:36179757 SUPPORT Human Clinical
"diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups"
Supports use of the Petzold et al. framework for subgroup curation.
PMID:29222573
Incidence and Causes of Overdiagnosis of Optic Neuritis.
1 finding
Overdiagnosis is common in referral cohorts, especially due to mimics.
"nearly 60% ... of patients referred for optic neuritis have an alternative diagnosis"
Show evidence (1 reference)
PMID:29222573 SUPPORT Human Clinical
"patients referred for optic neuritis have an alternative diagnosis"
Supports the differential-diagnosis section and diagnostic caution.
PMID:1734247
A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group.
1 finding
High-dose IV methylprednisolone accelerates visual recovery, while low-dose oral prednisone alone is not effective.
"Visual function recovered faster"
Show evidence (1 reference)
PMID:1734247 SUPPORT Human Clinical
"Visual function recovered faster"
Supports acute high-dose corticosteroid therapy.
PMID:29507942
Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial.
1 finding
Bioequivalent high-dose oral corticosteroids can be an alternative to IV corticosteroids.
"bioequivalent doses of oral corticosteroids may be used as an alternative"
Show evidence (1 reference)
PMID:29507942 SUPPORT Human Clinical
"bioequivalent doses of oral corticosteroids may be used as an alternative"
Supports high-dose oral corticosteroid equivalence to IV dosing.
PMID:37387119
Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review.
1 finding
Evidence for plasma exchange in acute NMO/NMOSD optic neuritis remains limited.
"inadequate data to determine whether PLEX effectively treats acute ON"
Show evidence (1 reference)
PMID:37387119 PARTIAL Human Clinical
"inadequate data to determine whether PLEX effectively treats acute ON"
Captures the treatment-evidence limitation for plasma exchange.
PMID:39963868
Incidence of optic neuritis among Afro-descendant, a cohort study.
1 finding
A 2018-2022 Martinique cohort estimated optic neuritis incidence and etiologic distribution.
"The overall incidence was 1.61"
Show evidence (1 reference)
PMID:39963868 SUPPORT Human Clinical
"The overall incidence was 1.61"
Supports epidemiology and subtype distribution.
PMID:38783085
MOG antibody-associated optic neuritis.
1 finding
MOGAD most frequently presents with optic neuritis and has characteristic clinical and radiologic features.
"MOGAD most frequently presents with optic neuritis"
Show evidence (1 reference)
PMID:38783085 SUPPORT Human Clinical
"MOGAD most frequently presents with optic neuritis"
Supports MOG-IgG-associated optic neuritis as a major antibody-defined subtype.
PMID:35377395
Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.
1 finding
Maintenance IVIG was associated with reduced relapse activity in adult MOGAD.
"maintenance IVIG was associated with a reduction in disease relapse"
Show evidence (1 reference)
PMID:35377395 SUPPORT Human Clinical
"maintenance IVIG was associated with a reduction in disease relapse"
Supports maintenance IVIG as relapse prevention for relapsing MOG-IgG-associated disease, including MOG-associated optic neuritis.
PMID:36810323
Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders
1 finding
OCT intereye-difference metrics are validated diagnostic parameters in AQP4-positive NMOSD optic neuritis.
"Results support the validation of the IED metrics"
Show evidence (1 reference)
PMID:36810323 SUPPORT Human Clinical
"Results support the validation of the IED metrics"
Supports OCT intereye-difference metrics as diagnostic support in AQP4-positive NMOSD-associated optic neuritis.
PMID:39231384
Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.
1 finding
OCT intereye-difference metrics have high diagnostic accuracy for MOG-IgG-associated optic neuritis.
"diagnostic accuracy of OCT-based IED metrics for ON was high"
Show evidence (1 reference)
PMID:39231384 SUPPORT Human Clinical
"diagnostic accuracy of OCT-based IED metrics for ON was high"
Supports OCT intereye-difference metrics as diagnostic support in MOG-IgG-associated optic neuritis.
PMID:38418465
Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis.
1 finding
MS genetic risk score plus demographics improves MS prediction after undifferentiated optic neuritis.
"one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold"
Show evidence (1 reference)
PMID:38418465 SUPPORT Human Clinical
"one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold"
Supports genetic-risk-score stratification as an emerging prognostic approach after first optic neuritis.
PMID:36822570
Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks.
1 finding
A large international cohort found most severe optic neuritis attacks improved with PLEX.
"Most ON attacks improved with PLEX"
Show evidence (1 reference)
PMID:36822570 SUPPORT Human Clinical
"Most ON attacks improved with PLEX"
Supports plasma exchange as escalation therapy in severe optic neuritis while preserving timing and severity as prognostic factors.
PMID:31050279
Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.
1 finding
Eculizumab substantially reduced relapse risk in AQP4-IgG-positive NMOSD.
"Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group"
Show evidence (1 reference)
PMID:31050279 SUPPORT Human Clinical
"Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group"
Supports complement C5 blockade as relapse prevention for AQP4-IgG-positive NMOSD, including the NMOSD-associated optic neuritis subtype context.
DOI:10.1016/j.ajo.2023.02.013
Visual Outcomes Following Plasma Exchange for Optic Neuritis: An International Multicenter Retrospective Analysis of 395 Optic Neuritis Attacks
No top-level findings curated for this source.
DOI:10.1038/s41433-024-03108-y
MOG antibody-associated optic neuritis
No top-level findings curated for this source.
DOI:10.1038/s41467-024-44917-9
Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis
No top-level findings curated for this source.
DOI:10.1136/jnnp-2022-330608
Diagnostic value of intereye difference metrics for optic neuritis in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders
No top-level findings curated for this source.
DOI:10.1177/13524585231224683
Prevalence of neuromyelitis optica spectrum disorder in the United States
No top-level findings curated for this source.
DOI:10.1212/nxi.0000000000200214
Acute Optic Neuropathy in Older Adults
No top-level findings curated for this source.
DOI:10.1212/nxi.0000000000200291
Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis
No top-level findings curated for this source.
DOI:10.3390/ijms242115986
Beyond Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies: Alternative Causes of Optic Neuritis
No top-level findings curated for this source.
DOI:10.7759/cureus.56094
A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 36 citations 2026-05-16T09:51:01.485894

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Optic Neuritis
  • MONDO ID: (if available)
  • Category: Neurological Disorder

Research Objectives

Please provide a comprehensive research report on Optic Neuritis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Optic Neuritis (ON): Disease Characteristics Research Report (Neurological Disorder)

Executive summary (current understanding)

Optic neuritis (ON) is an inflammatory optic neuropathy characterized clinically by acute/subacute visual loss with features such as impaired color/contrast vision and (in many cases) pain on eye movements; it is a common first manifestation of immune-mediated CNS demyelination and can also occur with antibody-mediated diseases (AQP4-IgG NMOSD; MOG-IgG–associated disease), infections, and systemic inflammatory disorders. A major 2022 international Delphi consensus (ICON) proposed standardized diagnostic criteria and a hierarchical classification to reduce misdiagnosis and to support subtype-specific management. (petzold2022diagnosisandclassification pages 1-3, petzold2022diagnosisandclassification pages 5-8)

Report scope and evidence sources

This report prioritizes 2022–2024 consensus, cohort, and multicenter studies retrieved in the current evidence set. Where key ontology identifiers (e.g., ICD-10, MeSH) were requested but not retrievable from the present corpus, the gap is explicitly flagged.

1. Disease information

1.1 What is the disease?

The ICON 2022 consensus addresses ON as a clinical syndrome requiring defined clinical features plus supportive paraclinical evidence (MRI/OCT/biomarkers) to establish definite ON; the work was motivated by frequent misdiagnosis and the expanding set of immune-mediated ON subtypes. (petzold2022diagnosisandclassification pages 1-3, petzold2022diagnosisandclassification pages 5-8)

Direct abstract quote (ICON 2022): “We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups.” (petzold2022diagnosisandclassification pages 1-3)

1.2 Key identifiers

  • OpenTargets/EFO: optic neuritis EFO_0007405 (OpenTargets Search: optic neuritis)
  • MONDO: autoimmune optic neuritis MONDO_0031013 (OpenTargets Search: optic neuritis)
  • ICD-10 / ICD-11 / MeSH / OMIM / Orphanet: not retrieved in current evidence corpus (gap).

A consolidated identifiers/synonyms table is provided below.

Preferred name MONDO / EFO / other supported ID ICD-10 / MeSH Key related entities / subtype context Common synonyms / alternative names Source URL(s) and publication date(s)
Optic neuritis EFO: EFO_0007405 (OpenTargets); MONDO not retrieved in current evidence not retrieved in current evidence Umbrella entity including MS-associated ON, MOG antibody-associated ON, and AQP4-IgG/NMOSD-associated ON (OpenTargets Search: optic neuritis, petzold2022diagnosisandclassification pages 1-3, petzold2022diagnosisandclassification pages 5-8) optic nerve inflammation; inflammatory optic neuropathy; demyelinating optic neuritis (spillers2024acomparativereview pages 1-2, petzold2022diagnosisandclassification pages 1-3) OpenTargets disease association context: no standalone public URL retrieved in current evidence, context-based ID mapping from OpenTargets (OpenTargets Search: optic neuritis); Petzold et al., Lancet Neurol 2022-09, https://doi.org/10.1016/S1474-4422(22)00200-9 (petzold2022diagnosisandclassification pages 1-3, petzold2022diagnosisandclassification pages 5-8)
Autoimmune optic neuritis MONDO: MONDO_0031013 not retrieved in current evidence Level-1/level-2 classification concept covering relapsing autoimmune ON subgroups such as AQP4-ON, MOG-ON, MS-ON, CRMP5-ON, RION/CRION (OpenTargets Search: optic neuritis, petzold2022diagnosisandclassification pages 5-8) autoimmune ON; relapsing autoimmune optic neuritis (petzold2022diagnosisandclassification pages 5-8) OpenTargets context for MONDO mapping: no standalone public URL retrieved in current evidence (OpenTargets Search: optic neuritis); Petzold et al., Lancet Neurol 2022-09, https://doi.org/10.1016/S1474-4422(22)00200-9 (petzold2022diagnosisandclassification pages 1-3, petzold2022diagnosisandclassification pages 5-8)
Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis No MONDO/EFO identifier retrieved in current evidence for this exact subtype not retrieved in current evidence MOG-ON; subtype of MOGAD; often bilateral, disc swelling, longitudinally extensive optic nerve lesion/perineuritis, steroid responsive but relapse-prone (jeyakumar2024mogantibodyassociatedoptic pages 1-2) MOG-ON; MOG antibody-associated optic neuritis; MOG-IgG-associated optic neuritis (jeyakumar2024mogantibodyassociatedoptic pages 1-2) Jeyakumar et al., Eye 2024-05, https://doi.org/10.1038/s41433-024-03108-y (jeyakumar2024mogantibodyassociatedoptic pages 1-2); Volpe et al., Neurol Neuroimmunol Neuroinflamm 2024-11, https://doi.org/10.1212/NXI.0000000000200291 (volpe2024diagnosticvalueof pages 1-2)
Aquaporin-4 antibody-associated optic neuritis / NMOSD-associated optic neuritis Related disease in OpenTargets: EFO: EFO_0004256 for neuromyelitis optica; exact ON subtype identifier not retrieved in current evidence not retrieved in current evidence AQP4-ON; NMOSD-ON; severe visual loss, poorer recovery, often relapsing autoimmune ON (greco2023beyondmyelinoligodendrocyte pages 1-2, oertel2023diagnosticvalueof pages 1-2, briggs2024prevalenceofneuromyelitis pages 1-3) AQP4-ON; AQP4-IgG optic neuritis; NMOSD-associated optic neuritis; neuromyelitis optica spectrum disorder optic neuritis (greco2023beyondmyelinoligodendrocyte pages 1-2, oertel2023diagnosticvalueof pages 1-2) Briggs & Shaia, Mult Scler 2024-01, https://doi.org/10.1177/13524585231224683 (briggs2024prevalenceofneuromyelitis pages 1-3); Oertel et al., J Neurol Neurosurg Psychiatry 2023-02, https://doi.org/10.1136/jnnp-2022-330608 (oertel2023diagnosticvalueof pages 1-2)
Multiple sclerosis-associated optic neuritis Related disease in OpenTargets: EFO: EFO_0003929 for relapsing-remitting multiple sclerosis; exact ON subtype identifier not retrieved in current evidence not retrieved in current evidence MS-ON; typical optic neuritis phenotype; often unilateral, painful, relatively favorable visual recovery (spillers2024acomparativereview pages 4-5, spillers2024acomparativereview pages 1-2, loginovic2024applyingagenetic pages 1-2) MS-ON; typical optic neuritis; multiple sclerosis-related optic neuritis (spillers2024acomparativereview pages 4-5, spillers2024acomparativereview pages 1-2) Loginovic et al., Nat Commun 2024-02, https://doi.org/10.1038/s41467-024-44917-9 (loginovic2024applyingagenetic pages 1-2, loginovic2024applyingagenetic pages 2-4); Petzold et al., Lancet Neurol 2022-09, https://doi.org/10.1016/S1474-4422(22)00200-9 (petzold2022diagnosisandclassification pages 1-3, petzold2022diagnosisandclassification pages 5-8)

Table: This table summarizes disease identifiers and commonly used names for optic neuritis and its major biomarker-defined or disease-associated subtypes, limited to identifiers explicitly supported by the retrieved evidence. It is useful for harmonizing terminology in a disease knowledge base while flagging identifier gaps not resolved in the current evidence set.

1.3 Synonyms and alternative names

Examples supported in the current corpus include “inflammatory optic neuropathy” and “demyelinating optic neuritis” in the context of typical (MS-associated) ON and biomarker-defined ON subtypes. (spillers2024acomparativereview pages 1-2, petzold2022diagnosisandclassification pages 1-3)

1.4 Evidence provenance (individual vs aggregated)

  • ICON diagnostic criteria and classification are aggregated expert consensus using a Delphi process across multiple specialties and regions. (petzold2022diagnosisandclassification pages 3-5, petzold2022diagnosisandclassification pages 5-8)
  • Plasma exchange outcomes and OCT diagnostic metrics are aggregated multicenter cohort evidence. (chen2023visualoutcomesfollowing pages 1-3, oertel2023diagnosticvalueof pages 1-2, volpe2024diagnosticvalueof pages 1-2)

2. Etiology

ON is etiologically heterogeneous. ICON emphasizes that “more than 60 conditions can be the subsequent diagnosis after an initial episode of optic neuritis or cause optic neuritis at any time during the disease” and proposes a top-level dichotomy to guide management: autoimmune (often relapsing) versus infectious/systemic (often monophasic). (petzold2022diagnosisandclassification pages 5-8)

2.1 Major immune-mediated causes

  • Multiple sclerosis–associated ON (MS-ON): A prototypical “typical” ON phenotype in many neurology/neuro-ophthalmology teaching datasets. A 2024 review summarizes that ON is the first demyelinating event in ~20% of MS and that ~50% of MS patients develop ON at some point. (spillers2024acomparativereview pages 4-5)
  • AQP4-IgG neuromyelitis optica spectrum disorder–associated ON (AQP4-ON / NMOSD-ON): NMOSD is a CNS demyelinating autoimmune disease that predominantly affects optic nerves and spinal cord, with near 80% having detectable anti–AQP4-IgG in one recent US EHR study’s background statement. (briggs2024prevalenceofneuromyelitis pages 1-3)
  • MOG-IgG–associated disease optic neuritis (MOG-ON): A 2024 MOG-ON review states MOGAD is distinct from MS and AQP4-NMOSD and that MOG-ON has characteristic clinical/MRI features (bilateral involvement, disc swelling, longitudinally extensive optic nerve hyperintensity and perineuritis); serum MOG-IgG detection by live cell-based assays in compatible phenotypes is described as highly specific. (jeyakumar2024mogantibodyassociatedoptic pages 1-2)

2.2 Infectious/systemic and other causes

ICON’s level-1 classification explicitly includes infectious ON, post-infectious ON, post-vaccination ON, and systemic conditions as typically monophasic groups, contrasted with autoimmune relapsing categories. (petzold2022diagnosisandclassification pages 5-8)

2.3 Genetic susceptibility and risk stratification (MS after ON)

A 2024 Nature Communications study reports that at first presentation with undifferentiated ON, combining an MS genetic risk score (MS-GRS) with demographic factors improved prediction of subsequent MS; one SD increase in MS-GRS increased the hazard of MS by ~1.3-fold and predicted-risk quartiles showed incident MS rates from 4% to 41%. (loginovic2024applyingagenetic pages 1-2, loginovic2024applyingagenetic pages 2-4)

Direct abstract quote (Loginovic 2024): “Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS).” (loginovic2024applyingagenetic pages 1-2)

2.4 Risk and protective factors

Risk-factor statements in general reviews (e.g., obesity, smoking, latitude) are mentioned but are not consistently quantified with primary-study effect sizes within the current evidence corpus; the only well-quantified, ON-specific risk stratification evidence in the present corpus is the MS-GRS model for post-ON MS diagnosis risk. (spillers2024acomparativereview pages 1-2, loginovic2024applyingagenetic pages 1-2)

3. Phenotypes (clinical presentation)

3.1 Core symptom complex

ICON clinical criteria define ON presentations as: - A (classic): “Monocular, sub-acute loss of vision associated with orbital pain worsening on eye movements, reduced contrast and colour vision, and relative afferent pupillary deficit (RAPD).” (petzold2022diagnosisandclassification pages 5-8) - B: painless variant with remaining A features (petzold2022diagnosisandclassification pages 5-8) - C: binocular vision loss with A/B features (petzold2022diagnosisandclassification pages 5-8)

A 2024 review summarizing ONTT reports pain with eye movement in ~90% and emphasizes generally favorable long-term visual outcomes in typical ON. (spillers2024acomparativereview pages 4-5)

3.2 Typical vs atypical phenotype patterns (examples with statistics)

From a 2023 review of serostatus-informed ON differentials: - NMOSD/AQP4-ON: severe visual loss and poorer recovery; bilateral involvement ~20%; chiasmal lesions up to ~two thirds in some series. (greco2023beyondmyelinoligodendrocyte pages 1-2) - MOG-ON: optic disc edema ~80%; bilateral involvement ~50%; often steroid-responsive. (greco2023beyondmyelinoligodendrocyte pages 1-2)

From a multicenter OCT study differentiating older-adult unilateral MOGAD-ON from NAION: - Eye pain strongly associated with MOGAD-ON (OR ~32.9); visual outcomes show worse nadir but better recovery in MOGAD-ON than NAION. (tisavipat2024acuteopticneuropathy pages 1-2)

3.3 Suggested HPO phenotype terms (non-exhaustive; for knowledge-base seeding)

(These are ontology suggestions; HPO IDs are not retrieved in current evidence and should be verified against HPO.) - Subacute vision loss; decreased visual acuity - Eye pain / pain with eye movement - Dyschromatopsia (acquired color vision deficit) - Reduced contrast sensitivity - Relative afferent pupillary defect - Optic disc edema / optic disc swelling - Visual field defect - Bilateral optic neuritis (in MOG-ON and some NMOSD-ON)

3.4 Quality of life impact

The US NMOSD prevalence study notes that lasting neurological deficits that impact quality of life are common in NMOSD, which frequently includes optic neuritis attacks. (briggs2024prevalenceofneuromyelitis pages 1-3)

4. Genetic / molecular information

4.1 Causal genes vs biomarker-defined disease

Classic ON is not typically monogenic; instead, modern practice emphasizes biomarker-defined autoimmune ON subtypes and associated autoimmune mechanisms.

4.2 Key biomarkers in ICON classification (Level 2)

ICON Level-2 autoimmune ON subtypes include: - AQP4-ON, MOG-ON, CRMP5-ON, MS-ON, and clinical entities such as SION/RION/CRION. (petzold2022diagnosisandclassification pages 5-8)

4.3 Target/therapy linkage (knowledge-base enrichment)

OpenTargets association evidence in this corpus links optic neuritis and related demyelinating diseases to therapy targets used in practice (e.g., NR3C1 reflecting glucocorticoid pathway for acute therapy; and NMOSD targets including C5, IL6R, CD19 reflecting approved relapse-prevention therapies). (OpenTargets Search: optic neuritis)

5. Environmental information

ICON’s level-1 framework explicitly includes post-infectious and post-vaccination ON categories (typically monophasic), supporting infection/immune-trigger environmental contributions in subsets. (petzold2022diagnosisandclassification pages 5-8)

A specific infectious trigger example in the current corpus (observational) includes optic neuritis temporally associated with mild COVID-19 more often in MOG-ON than AQP4-ON, with detailed timing statistics. (jeyakumar2024mogantibodyassociatedoptic pages 1-2)

6. Mechanism / pathophysiology

6.1 Mechanistic framing (ICON 2022)

ICON highlights that advances in autoantibody diagnostics, imaging, and OCT have changed ON phenotyping, and that timely identification of relapsing autoimmune subtypes is clinically critical because delayed or wrong treatment can be catastrophic for vision. (petzold2022diagnosisandclassification pages 5-8)

6.2 Antibody-mediated vs oligodendrocyte-mediated paradigms

  • AQP4-IgG NMOSD: conceptualized as antibody-mediated astrocytopathy in many expert sources; in the present evidence set, NMOSD is characterized by anti–AQP4-IgG seropositivity in the majority of cases and severe acute deficits. (briggs2024prevalenceofneuromyelitis pages 1-3, spillers2024acomparativereview pages 4-5)
  • MOGAD/MOG-ON: described as an oligodendrogliopathy, with characteristic radiology and frequent steroid-responsiveness but relapse risk with rapid tapering. (jeyakumar2024mogantibodyassociatedoptic pages 1-2)

6.3 Suggested GO biological process terms (conceptual; verify against GO)

  • Immune-mediated demyelination
  • Complement activation (especially NMOSD)
  • Leukocyte migration / neuroinflammation
  • Axon degeneration / neuronal death

6.4 Suggested Cell Ontology (CL) terms (conceptual; verify)

  • Oligodendrocyte
  • Astrocyte
  • Microglia
  • Retinal ganglion cell

7. Anatomical structures affected

7.1 Organ/system level

  • Primary: optic nerve (cranial nerve II) (spillers2024acomparativereview pages 1-2)
  • CNS/visual pathway involvement varies by etiology (MS, NMOSD, MOGAD). (spillers2024acomparativereview pages 4-5, jeyakumar2024mogantibodyassociatedoptic pages 1-2)

7.2 Suggested UBERON structures (conceptual; verify)

  • Optic nerve
  • Retina (particularly retinal nerve fiber layer and ganglion cell layer measured by OCT)
  • Optic chiasm (notably in NMOSD-associated patterns) (greco2023beyondmyelinoligodendrocyte pages 1-2)

7.3 Lateralization/localization patterns

  • Typical ON often unilateral; MOG-ON frequently bilateral at onset; NMOSD can be bilateral in a minority and can involve chiasm. (greco2023beyondmyelinoligodendrocyte pages 1-2, jeyakumar2024mogantibodyassociatedoptic pages 1-2)

8. Temporal development

ICON operationalizes time windows for interpretation of clinical/paraclinical evidence and provides definitions for acute/subacute/chronic presentations; paraclinical criteria differ in acute versus ≥3-month phases. (petzold2022diagnosisandclassification pages 5-8)

MOGAD shows a biphasic age distribution with peaks in childhood (5–10 years) and young/middle adulthood (20–45 years). (jeyakumar2024mogantibodyassociatedoptic pages 1-2)

9. Inheritance and population

9.1 Epidemiology of ON and related diseases

  • General ON incidence (UK/USA): A 2024 genetic risk-stratification study cites population-based incidence of 3.7–5.1 per 100,000 person-years in the UK and USA. (loginovic2024applyingagenetic pages 1-2)
  • MOGAD epidemiology: incidence ~1.6–4.8 per million/year, prevalence 1.3–2.5 per 100,000. (jeyakumar2024mogantibodyassociatedoptic pages 1-2)
  • NMOSD (US 2022 prevalence): 6.88/100,000, with higher prevalence in Black individuals (12.99/100,000) and Asian individuals (9.41/100,000), and female predominance. (briggs2024prevalenceofneuromyelitis pages 1-3)

9.2 Sex and demographic patterns

  • NMOSD female prevalence 9.48/100,000 vs male 3.52/100,000; female:male ~3.5:1 in US EHR data. (briggs2024prevalenceofneuromyelitis pages 1-3)
  • ON cohorts and classic ON teaching often emphasize young adult predominance and female predominance. (spillers2024acomparativereview pages 1-2, loginovic2024applyingagenetic pages 1-2)

10. Diagnostics

10.1 ICON 2022 diagnostic criteria (key concepts)

ICON defines definite ON based on clinical pattern plus paraclinical support. (petzold2022diagnosisandclassification pages 5-8)

Paraclinical tests and thresholds (ICON Panel 1): - OCT: optic disc swelling acutely or inter-eye difference mGCIPL >4% or >4 μm or pRNFL >5% or >5 μm within ≥3 months after onset (petzold2022diagnosisandclassification pages 5-8) - MRI: optic nerve/sheath contrast enhancement acutely or intrinsic optic nerve signal increase within ≥3 months (petzold2022diagnosisandclassification pages 5-8) - Biomarkers: AQP4-IgG, MOG-IgG, CRMP5-IgG seropositivity, or CSF oligoclonal bands (intrathecal IgG) (petzold2022diagnosisandclassification pages 5-8)

10.2 Recent (2023–2024) validation and practical implementation of OCT criteria

  • In AQP4+ NMOSD, inter-eye OCT difference metrics showed excellent discrimination between unilateral NMOSD-ON and controls (AUC up to 0.96 with sensitivity/specificity ~75–98% depending on metric). (oertel2023diagnosticvalueof pages 1-2)
  • In MOG-ON, the mGCIP inter-eye percentage difference was highly sensitive (92%), with notably lower sensitivity in bilateral ON compared with unilateral ON. (volpe2024diagnosticvalueof pages 1-2)

10.3 Differential diagnosis (selected, evidence-backed examples)

  • Older adults: differentiating MOGAD-ON from NAION using eye pain, optic disc anatomy, and OCT swelling patterns; caution regarding low-titer false-positive MOG-IgG in NAION (8% among those tested at Mayo in one cohort). (tisavipat2024acuteopticneuropathy pages 1-2)

11. Outcome / prognosis

11.1 Visual recovery in typical ON and MS risk

  • Typical ON generally has favorable long-term vision; a 2024 review summarizing ONTT reports ~72% maintained 20/20 vision in both eyes at 15 years and pain with eye movement ~90% in typical ON. (spillers2024acomparativereview pages 4-5)
  • MS conversion risk after undifferentiated ON can be stratified using MS-GRS models (4% to 41% MS incidence across risk quartiles). (loginovic2024applyingagenetic pages 1-2)

11.2 Outcomes with plasma exchange (PLEX) for severe ON (2023 multicenter data)

A large 2023 international multicenter retrospective cohort (395 attacks) reported median final VA ~20/25 after PLEX but with substantial residual severe vision loss in a subset (20.5% ≤20/200). Outcomes varied by etiology: MOGAD-ON had the best outcomes (median 20/20; 1% ≤20/200), while AQP4+ NMOSD had higher proportions with poor final VA (≈31% ≤20/200). Time-to-PLEX was associated with outcomes (median 2.4 vs 3.3 weeks in good vs poor outcome groups; p<0.001). (chen2023visualoutcomesfollowing pages 5-6, chen2023visualoutcomesfollowing pages 18-25)

The PLEX paper’s tables/figures supporting these outcome stratifications were retrieved as document images (Figures 2–4; Tables 1–3). (chen2023visualoutcomesfollowing media 1c706b2b)

12. Treatment

12.1 Acute attack treatment (general)

ICON’s framing and recent reviews emphasize that acute treatment should be time-sensitive, especially for atypical/autoimmune cases at risk of irreversible injury. (petzold2022diagnosisandclassification pages 5-8, spillers2024acomparativereview pages 1-2)

Common acute strategies discussed in current reviews include: - High-dose IV glucocorticoids (e.g., IV methylprednisolone) - Escalation to plasma exchange (PLEX) for severe and/or steroid-refractory attacks - IVIG in selected situations (evidence base remains incomplete) (spillers2024acomparativereview pages 6-7)

12.2 Evidence for PLEX in severe ON

The 2023 multicenter retrospective analysis supports meaningful recovery in many severe cases treated with PLEX and suggests improved outcomes compared with matched severe ONTT subsets (e.g., final VA worse than 20/40: 12% PLEX vs 33% ONTT IVMP without PLEX; p=0.04). (chen2023visualoutcomesfollowing pages 1-3, chen2023visualoutcomesfollowing pages 6-8)

12.3 Treatment considerations by subtype

  • MOG-ON: described as largely corticosteroid-responsive, but relapse risk is common with early/rapid tapering, motivating research on steroid-sparing relapse prevention. (jeyakumar2024mogantibodyassociatedoptic pages 1-2)
  • AQP4+ NMOSD: relapse prevention is central; the present evidence set includes real-world effectiveness/safety data for complement inhibition with eculizumab (attack-free 88% during therapy; systemic infection risks and vaccine-timing issues). (spillers2024acomparativereview pages 8-9)

12.4 Suggested MAXO terms (conceptual; verify)

  • High-dose intravenous glucocorticoid therapy
  • Therapeutic plasma exchange
  • Intravenous immunoglobulin therapy
  • Long-term immunosuppression / immunomodulation (subtype-specific)

13. Prevention

No primary prevention is established for idiopathic/typical ON. Secondary/tertiary prevention is subtype-driven: - Prevent relapse and disability in NMOSD/MOGAD via appropriate long-term therapy and monitoring. (petzold2022diagnosisandclassification pages 5-8, jeyakumar2024mogantibodyassociatedoptic pages 1-2)

14. Other species / natural disease

Not resolved in the current evidence corpus.

15. Model organisms

Not resolved with citeable model-organism primary literature in the current evidence corpus. (Preclinical ON/EAE papers were retrieved during search but were not converted into citeable evidence snippets in this run; therefore they are not included as claims here.)

Recent developments (2022–2024) and real-world implementation highlights

The following table compiles the most actionable, recent quantitative evidence for clinical implementation (ICON 2022 criteria; OCT thresholds validation in AQP4+ NMOSD and MOG-ON; PLEX outcomes; NMOSD prevalence; MS genetic risk stratification).

Topic Key finding/statistic Population/study design Publication (authors, journal) Year/month DOI/URL Evidence type
Diagnostic criteria (ICON/International Consensus) Clinical criteria: A = monocular, subacute vision loss with orbital pain on eye movement, reduced contrast/color vision, RAPD; B = painless with all other features of A; C = binocular loss with features of A or B. Paraclinical thresholds: OCT mGCIPL inter-eye difference >4% or >4 μm or pRNFL >5% or >5 μm within ≥3 months after onset; MRI symptomatic optic nerve/sheath contrast enhancement acutely or intrinsic T2 signal increase within ≥3 months; biomarkers: AQP4, MOG, CRMP5 seropositivity or CSF oligoclonal bands. Definite ON: A + 1 paraclinical test; B + 2 tests of different modality; C + MRI + 1 other paraclinical test (petzold2022diagnosisandclassification pages 5-8) International Delphi consensus diagnostic/classification framework for optic neuritis Petzold et al., Lancet Neurology 2022/Sep 10.1016/S1474-4422(22)00200-9; https://doi.org/10.1016/S1474-4422(22)00200-9 Guideline/consensus (human expert Delphi)
OCT thresholds validated in AQP4+ NMOSD-ON Proposed thresholds tested: pRNFL IEAD 5 μm, IEPD 5%; GCIPL IEAD 4 μm, IEPD 4%. NMOSD-ON vs healthy controls: pRNFL IEAD AUC 0.95, specificity 82%, sensitivity 86%; GCIPL IEAD AUC 0.93, specificity 98%, sensitivity 75%; pRNFL IEPD AUC 0.96, specificity 87%, sensitivity 89%; GCIPL IEPD AUC 0.94, specificity 96%, sensitivity 82%. NMOSD-ON vs NMOSD-NON: pRNFL IEAD AUC 0.92, specificity 77%, sensitivity 86%; GCIPL IEAD AUC 0.87, specificity 85%, sensitivity 75%; pRNFL IEPD AUC 0.94, specificity 82%, sensitivity 89%; GCIPL IEPD AUC 0.88, specificity 82%, sensitivity 82% (oertel2023diagnosticvalueof pages 1-2) Multicenter study of 28 AQP4+ NMOSD unilateral ON, 45 AQP4+ NMOSD without ON history, 62 healthy controls Oertel et al., JNNP 2023/Feb 10.1136/jnnp-2022-330608; https://doi.org/10.1136/jnnp-2022-330608 Human multicenter diagnostic cohort
OCT thresholds validated in MOG-ON Using ICON-related published cutoffs (>4% or >4 μm mGCIP; >5% or >5 μm pRNFL), pooled MOG-ON analysis showed mGCIP IEPD sensitivity 92%, mGCIP IEAD 88%, pRNFL 84%; specificity: mGCIP IEPD 82%, mGCIP IEAD 82%, pRNFL IEPD 82%, pRNFL IEAD 79%. In unilateral ON, diagnostic sensitivity was >99% for all metrics; in bilateral ON, sensitivity fell to 61%–78% (volpe2024diagnosticvalueof pages 1-2) Multicenter validation study of 66 participants (33 MOG-ON, 33 controls) Volpe et al., Neurology Neuroimmunology & Neuroinflammation 2024/Nov 10.1212/NXI.0000000000200291; https://doi.org/10.1212/NXI.0000000000200291 Human multicenter diagnostic cohort
PLEX outcomes in severe ON 395 ON attacks in 317 patients; median time from vision loss onset to PLEX 2.6 weeks (IQR 1.4–4.0); median VA at PLEX count fingers (IQR 20/200–hand motion); median final VA 20/25 (IQR 20/20–20/60); 81 attacks (20.5%) ended with final VA 20/200 or worse. Poorer outcomes associated with older age (p=0.002), worse VA at PLEX (p<0.001), and longer delay to PLEX (p<0.001). In matched comparison, final VA worse than 20/40 occurred in 12% (6/50) of PLEX-treated attacks vs 33% (6/18) in ONTT IVMP without PLEX (p=0.04) (chen2023visualoutcomesfollowing pages 1-3) International multicenter retrospective analysis; etiologies included MS (108), MOGAD (92), AQP4+ NMOSD (75), seronegative NMOSD (34), idiopathic (83) Chen et al., American Journal of Ophthalmology 2023/Aug 10.1016/j.ajo.2023.02.013; https://doi.org/10.1016/j.ajo.2023.02.013 Human multicenter retrospective cohort
MOGAD / MOG-ON epidemiology and phenotype MOGAD incidence ~1.6–4.8 per million/year; prevalence 1.3–2.5 per 100,000; biphasic onset peaks at 5–10 years and 20–45 years. Optic neuritis is the commonest adult presentation (~30–60%). Distinctive features include frequent bilateral onset, optic disc swelling, headache, longitudinally extensive optic nerve hyperintensity, and optic perineuritis on MRI; serum live cell-based assay MOG-IgG is highly specific (jeyakumar2024mogantibodyassociatedoptic pages 1-2) Narrative review synthesizing cohort/registry data on MOG antibody-associated optic neuritis Jeyakumar et al., Eye 2024/May 10.1038/s41433-024-03108-y; https://doi.org/10.1038/s41433-024-03108-y Human review of cohort/registry evidence
NMOSD prevalence in the US 2022 prevalence 6.88/100,000 from 1,772 patients among 25,743,039 EHR patients. By race: Black 12.99/100,000, Asian 9.41/100,000, White 5.58/100,000. Among females, prevalence 9.48/100,000; Black and Asian females had 2.65× and 1.94× higher prevalence than White females. Male prevalence 3.52/100,000; female:male ratio about 3.5:1. Estimated US burden: 15,413 females and 6,233 males (~22,000 total) (briggs2024prevalenceofneuromyelitis pages 1-3) Cross-sectional prevalence study using nationwide aggregated EHR data from 55 healthcare organizations Briggs & Shaia, Multiple Sclerosis Journal 2024/Jan 10.1177/13524585231224683; https://doi.org/10.1177/13524585231224683 Human population-based EHR epidemiology
MS risk stratification after ON using genetics In undifferentiated ON, one SD increase in MS genetic risk score (MS-GRS) increased hazard of MS 1.3-fold; multivariable HR 1.29 (95% CI 1.07–1.55, P=0.0067). Predicted-risk quartiles developed incident MS at rates from 4% (95% CI 0.5–7%, lowest quartile) to 41% (95% CI 33–49%, highest quartile). Background rates in study: ON incidence cited as 3.7–5.1 per 100,000 person-years in UK/USA; by 5 years, about 20% of undifferentiated ON diagnosed with MS; by 15 years, up to 50% of ON (excluding bilateral presentation) diagnosed with MS. In UK Biobank, among 545 undifferentiated ON cases, 124 (22.8%) developed MS during median 18.4 years follow-up (loginovic2024applyingagenetic pages 1-2, loginovic2024applyingagenetic pages 2-4) UK Biobank primary analysis with replication in Geisinger and FinnGen; genetic risk modeling in ON Loginovic et al., Nature Communications 2024/Feb 10.1038/s41467-024-44917-9; https://doi.org/10.1038/s41467-024-44917-9 Human genomic cohort / prognostic modeling

Table: This table compiles high-yield quantitative findings from 2022-2024 on optic neuritis diagnostic criteria, imaging thresholds, outcomes, epidemiology, and MS risk prediction. It is useful as a compact evidence summary for knowledge-base curation and citation-backed reporting.

Limitations and evidence gaps (important for knowledge-base curation)

  • ICD-10/ICD-11, MeSH, OMIM, and Orphanet identifiers were not retrievable from the current corpus and should be added from dedicated ontology sources in a subsequent retrieval step.
  • HPO/GO/UBERON/CL/MAXO term mappings are provided as suggestions and require ontology-validated IDs.
  • Animal model evidence was retrieved in searches but not captured as citeable evidence snippets in the current run; therefore, the model-organism section is left as “not resolved” rather than inferred.

References

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  14. (chen2023visualoutcomesfollowing pages 1-3): John J. Chen, Eoin P. Flanagan, Sean J. Pittock, Nicole Caroline Stern, Nanthaya Tisavipat, M. Tariq Bhatti, Kevin D. Chodnicki, Deena A. Tajfirouz, Sepideh Jamali, Amy Kunchok, Eric R. Eggenberger, Marie A. Di Nome, Elias S. Sotirchos, Eleni S. Vasileiou, Amanda D. Henderson, Anthony C. Arnold, Laura Bonelli, Heather E. Moss, Sylvia Elizabeth Villarreal Navarro, Tanyatuth Padungkiatsagul, Hadas Stiebel-Kalish, Itay Lotan, Adi Wilf-Yarkoni, Helen Danesh-Meyer, Stefan Ivanov, Saif Huda, Mirasol Forcadela, David Hodge, Pascale Poullin, Julie Rode, Caroline Papeix, Samir Saheb, Marine Boudot de la Motte, Catherine Vignal, Yael Hacohen, Julie Pique, Elisabeth Maillart, Romain Deschamps, Bertrand Audoin, and Romain Marignier. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 optic neuritis attacks. American Journal of Ophthalmology, 252:213-224, Aug 2023. URL: https://doi.org/10.1016/j.ajo.2023.02.013, doi:10.1016/j.ajo.2023.02.013. This article has 78 citations and is from a domain leading peer-reviewed journal.

  15. (tisavipat2024acuteopticneuropathy pages 1-2): Nanthaya Tisavipat, Hadas Stiebel-Kalish, Dahlia Palevski, Omer Y. Bialer, Heather E. Moss, Pareena Chaitanuwong, Tanyatuth Padungkiatsagul, Amanda D. Henderson, Elias S. Sotirchos, Shonar Singh, Abdul-Rahman Salman, Deena A. Tajfirouz, Kevin D. Chodnicki, Sean J. Pittock, Eoin P. Flanagan, and John J. Chen. Acute optic neuropathy in older adults. Neurology Neuroimmunology & Neuroinflammation, May 2024. URL: https://doi.org/10.1212/nxi.0000000000200214, doi:10.1212/nxi.0000000000200214. This article has 17 citations.

  16. (chen2023visualoutcomesfollowing pages 5-6): John J. Chen, Eoin P. Flanagan, Sean J. Pittock, Nicole Caroline Stern, Nanthaya Tisavipat, M. Tariq Bhatti, Kevin D. Chodnicki, Deena A. Tajfirouz, Sepideh Jamali, Amy Kunchok, Eric R. Eggenberger, Marie A. Di Nome, Elias S. Sotirchos, Eleni S. Vasileiou, Amanda D. Henderson, Anthony C. Arnold, Laura Bonelli, Heather E. Moss, Sylvia Elizabeth Villarreal Navarro, Tanyatuth Padungkiatsagul, Hadas Stiebel-Kalish, Itay Lotan, Adi Wilf-Yarkoni, Helen Danesh-Meyer, Stefan Ivanov, Saif Huda, Mirasol Forcadela, David Hodge, Pascale Poullin, Julie Rode, Caroline Papeix, Samir Saheb, Marine Boudot de la Motte, Catherine Vignal, Yael Hacohen, Julie Pique, Elisabeth Maillart, Romain Deschamps, Bertrand Audoin, and Romain Marignier. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 optic neuritis attacks. American Journal of Ophthalmology, 252:213-224, Aug 2023. URL: https://doi.org/10.1016/j.ajo.2023.02.013, doi:10.1016/j.ajo.2023.02.013. This article has 78 citations and is from a domain leading peer-reviewed journal.

  17. (chen2023visualoutcomesfollowing pages 18-25): John J. Chen, Eoin P. Flanagan, Sean J. Pittock, Nicole Caroline Stern, Nanthaya Tisavipat, M. Tariq Bhatti, Kevin D. Chodnicki, Deena A. Tajfirouz, Sepideh Jamali, Amy Kunchok, Eric R. Eggenberger, Marie A. Di Nome, Elias S. Sotirchos, Eleni S. Vasileiou, Amanda D. Henderson, Anthony C. Arnold, Laura Bonelli, Heather E. Moss, Sylvia Elizabeth Villarreal Navarro, Tanyatuth Padungkiatsagul, Hadas Stiebel-Kalish, Itay Lotan, Adi Wilf-Yarkoni, Helen Danesh-Meyer, Stefan Ivanov, Saif Huda, Mirasol Forcadela, David Hodge, Pascale Poullin, Julie Rode, Caroline Papeix, Samir Saheb, Marine Boudot de la Motte, Catherine Vignal, Yael Hacohen, Julie Pique, Elisabeth Maillart, Romain Deschamps, Bertrand Audoin, and Romain Marignier. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 optic neuritis attacks. American Journal of Ophthalmology, 252:213-224, Aug 2023. URL: https://doi.org/10.1016/j.ajo.2023.02.013, doi:10.1016/j.ajo.2023.02.013. This article has 78 citations and is from a domain leading peer-reviewed journal.

  18. (chen2023visualoutcomesfollowing media 1c706b2b): John J. Chen, Eoin P. Flanagan, Sean J. Pittock, Nicole Caroline Stern, Nanthaya Tisavipat, M. Tariq Bhatti, Kevin D. Chodnicki, Deena A. Tajfirouz, Sepideh Jamali, Amy Kunchok, Eric R. Eggenberger, Marie A. Di Nome, Elias S. Sotirchos, Eleni S. Vasileiou, Amanda D. Henderson, Anthony C. Arnold, Laura Bonelli, Heather E. Moss, Sylvia Elizabeth Villarreal Navarro, Tanyatuth Padungkiatsagul, Hadas Stiebel-Kalish, Itay Lotan, Adi Wilf-Yarkoni, Helen Danesh-Meyer, Stefan Ivanov, Saif Huda, Mirasol Forcadela, David Hodge, Pascale Poullin, Julie Rode, Caroline Papeix, Samir Saheb, Marine Boudot de la Motte, Catherine Vignal, Yael Hacohen, Julie Pique, Elisabeth Maillart, Romain Deschamps, Bertrand Audoin, and Romain Marignier. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 optic neuritis attacks. American Journal of Ophthalmology, 252:213-224, Aug 2023. URL: https://doi.org/10.1016/j.ajo.2023.02.013, doi:10.1016/j.ajo.2023.02.013. This article has 78 citations and is from a domain leading peer-reviewed journal.

  19. (spillers2024acomparativereview pages 6-7): Noah J Spillers, Patrick M Luther, Norris C Talbot, Evan J Kidder, Connor A Doyle, Salim C Lutfallah, Alyssa G Derouen, Sridhar Tirumala, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D Kaye, and Giustino Varrassi. A comparative review of typical and atypical optic neuritis: advancements in treatments, diagnostics, and prognosis. Cureus, Mar 2024. URL: https://doi.org/10.7759/cureus.56094, doi:10.7759/cureus.56094. This article has 11 citations.

  20. (chen2023visualoutcomesfollowing pages 6-8): John J. Chen, Eoin P. Flanagan, Sean J. Pittock, Nicole Caroline Stern, Nanthaya Tisavipat, M. Tariq Bhatti, Kevin D. Chodnicki, Deena A. Tajfirouz, Sepideh Jamali, Amy Kunchok, Eric R. Eggenberger, Marie A. Di Nome, Elias S. Sotirchos, Eleni S. Vasileiou, Amanda D. Henderson, Anthony C. Arnold, Laura Bonelli, Heather E. Moss, Sylvia Elizabeth Villarreal Navarro, Tanyatuth Padungkiatsagul, Hadas Stiebel-Kalish, Itay Lotan, Adi Wilf-Yarkoni, Helen Danesh-Meyer, Stefan Ivanov, Saif Huda, Mirasol Forcadela, David Hodge, Pascale Poullin, Julie Rode, Caroline Papeix, Samir Saheb, Marine Boudot de la Motte, Catherine Vignal, Yael Hacohen, Julie Pique, Elisabeth Maillart, Romain Deschamps, Bertrand Audoin, and Romain Marignier. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 optic neuritis attacks. American Journal of Ophthalmology, 252:213-224, Aug 2023. URL: https://doi.org/10.1016/j.ajo.2023.02.013, doi:10.1016/j.ajo.2023.02.013. This article has 78 citations and is from a domain leading peer-reviewed journal.

  21. (spillers2024acomparativereview pages 8-9): Noah J Spillers, Patrick M Luther, Norris C Talbot, Evan J Kidder, Connor A Doyle, Salim C Lutfallah, Alyssa G Derouen, Sridhar Tirumala, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D Kaye, and Giustino Varrassi. A comparative review of typical and atypical optic neuritis: advancements in treatments, diagnostics, and prognosis. Cureus, Mar 2024. URL: https://doi.org/10.7759/cureus.56094, doi:10.7759/cureus.56094. This article has 11 citations.

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