The 2022 International Consensus Diagnostic Criteria for Optic Neuritis was developed to provide a standardized and comprehensive approach for optic neuritis diagnosis (ON), taking into account the broad spectrum of clinical presentations and underlying causes. The criteria focus on differentiating the various forms of optic neuritis, including idiopathic ON, optic neuritis associated with multiple sclerosis (MS), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other systemic or infectious causes.

### Key Aspects of the 2022 International Diagnostic Criteria for Optic Neuritis:

1. Core Clinical Features:

1. Acute/subacute onset: Optic neuritis typically presents with sudden or gradually worsening vision loss, which progresses over hours to days.
2. Monocular or binocular: Most cases of ON involve one eye, but bilateral ON can occur, particularly in MOG-ON.
3. Pain: Often, but not always, associated with pain, especially during eye movement (more common in MS-ON and idiopathic ON).
4. Vision loss: Ranges from mild to severe, often associated with reduced color vision (dyschromatopsia) and decreased visual acuity.

2. Required Diagnostic Criteria:

To diagnose optic neuritis, the following general criteria must be met:

Vision loss: Subacute vision loss in one or both eyes, often accompanied by pain on eye movement.

Relative afferent pupillary defect (RAPD): Present in unilateral or asymmetric cases of optic neuritis.

Fundoscopic examination: Optic disc swelling may be present (especially in anterior optic neuritis), but many cases present with a normal-appearing optic nerve (retrobulbar ON).

Exclusion of alternative causes: Differential diagnoses such as ischemic optic neuropathy, compressive optic neuropathy, and hereditary optic neuropathies must be excluded.

3. Supportive Diagnostic Tests:

1. Magnetic Resonance Imaging (MRI): MRI of the optic nerves, brain, and orbits should be conducted to detect:
   1. Inflammation or demyelination of the optic nerve.
   2. Brain lesions consistent with MS or NMOSD.
2. Serologic testing: For AQP4-IgG and MOG-IgG antibodies to differentiate NMOSD and MOGAD from other forms of optic neuritis.

Assesses the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness to detect optic nerve damage.

The 2022 International Consensus Diagnostic Criteria for Optic Neuritis include optical coherence tomography (OCT). The diagnostic value of intereye difference (IED) metrics is high for ON in patients with multiple sclerosis and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders, but unknown in Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis(MOG-ON).

A multicenter validation study was conducted on the published IED cutoff values (>4% or >4 μm in the macular ganglion cell and inner plexiform layer [mGCIP] or >5% or >5 μm in the peripapillary retinal nerve fiber layer [pRNFL]) in individuals with MOG-ON and age-matched and sex-matched healthy controls (HCs). Structural data were acquired with Spectralis spectral-domain OCT >6 months after ON. Volpe et al. calculated sensitivity, specificity, and receiver operating characteristics for both intereye percentage (IEPD) and absolute difference (IEAD).

A total of 66 individuals were included (MOG-ON N = 33; HCs N = 33). ON was unilateral in 20 and bilateral in 13 subjects. In the pooled analysis, the mGCIP IEPD was the most sensitive (92%), followed by the mGCIP IEAD (88%) and pRNFL (84%). The same pattern was found for the specificity (mGCIP IEPD 82%, IEAD 82%; pRNFL IEPD 82%, IEAD 79%).In subgroup analyses, the diagnostic sensitivity was higher in subjects with unilateral ON (>99% for all metrics) compared with bilateral ON (61%-78%).

In individuals with MOG-ON, the diagnostic accuracy of OCT-based IED metrics for ON was high, especially for mGCIP IEPD.

Classification of evidence: This study provides Class III evidence that the intereye difference in OCT can distinguish between those with MOG and normal controls ¹⁾

 The 2022 criteria acknowledge different subtypes of optic neuritis, with distinct diagnostic pathways for each:

 a. **Multiple Sclerosis-Associated Optic Neuritis (MS-ON)**:
    - Typically unilateral with pain on eye movement.
    - MRI may reveal white matter lesions in the brain consistent with MS.
    - More likely to occur in younger adults (20-40 years).

 b. **Aquaporin-4 Antibody-Associated Neuromyelitis Optica Spectrum Disorder (AQP4-NMOSD)**:
    - Often severe and recurrent, with bilateral optic neuritis common.
    - Serologic testing for **AQP4-IgG antibodies** is crucial.
    - MRI may show longitudinally extensive optic nerve lesions.

 c. **Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis (MOG-ON)**:
    - Typically bilateral and associated with significant optic disc swelling.
    - Vision recovery is often better than in AQP4-NMOSD.
    - Serologic testing for **MOG-IgG antibodies** is required.
    - MRI shows anterior optic nerve involvement.

 d. **Idiopathic Optic Neuritis**:
    - Diagnosis of exclusion when no specific cause (e.g., MS, NMOSD, MOGAD) is identified.
    - Typically unilateral with pain on eye movement.
    - MRI may be normal or show isolated optic nerve inflammation.

 e. **Systemic or Infectious Optic Neuritis**:
    - May be associated with systemic autoimmune conditions (e.g., sarcoidosis, lupus) or infections (e.g., syphilis, tuberculosis).
    - Requires additional diagnostic tests (e.g., blood tests, imaging, biopsy) to identify the underlying cause.

5. Patient-Reported Outcome Measures:

1. Recognizing the limitations of traditional diagnostic metrics, the criteria emphasize the importance of patient-reported outcome measures (PROMs) to capture the full scope of vision-related disability, quality of life, and the psychological impact of vision loss.

6. Long-Term Monitoring:

1. Regular follow-up with MRI, OCT, and clinical exams is advised to monitor disease progression, especially in relapsing conditions like NMOSD and MOGAD.
2. Monitoring for conversion to multiple sclerosis in patients with isolated optic neuritis is crucial, particularly in those with high-risk brain MRI findings (e.g., white matter lesions).

### Conclusion: The 2022 International Consortium for Optic Neuritis Diagnostic Criteria provides a standardized framework for diagnosing optic neuritis and its various subtypes. By incorporating serological testing, imaging, and patient-reported outcomes, the criteria aim to improve diagnostic accuracy and guide appropriate treatment for patients with different forms of optic neuritis, including those related to MS, NMOSD, MOGAD, and other systemic conditions.