Optic neuritis is an important cause of acute or subacute visual loss. In clinical practice, optic neuritis must often be distinguished from other optic neuropathies, retinal diseases, anterior-segment or ocular media disorders, non-organic visual loss, and other mimics. The 2022 International Criteria for Optic Neuritis were developed to standardize the diagnosis of optic neuritis, but their performance in Chinese clinical settings, where aquaporin-4 immunoglobulin G positive and myelin oligodendrocyte glycoprotein immunoglobulin G positive optic neuritis are relatively common, remains uncertain.
This multicenter prospective observational study is enrolling patients with acute or subacute visual loss or visual dysfunction in whom optic neuritis is included in the differential diagnosis. The study is designed to evaluate the diagnostic performance of the 2022 International Criteria for Optic Neuritis alone and with an antibody-stratified adjunct. The index classifications will be compared with an expert-adjudicated reference-standard diagnosis. No experimental treatment is assigned by the study. All diagnostic tests and treatments are determined by the treating clinicians according to routine clinical care. Study data are collected using a structured protocol-defined case report form.
Individuals presenting with a new acute or subacute episode of visual loss or visual dysfunction in one or both eyes, for whom optic neuritis is considered a reasonable differential diagnosis by the treating clinical team at the initial clinical assessment and before final diagnostic adjudication.
Symptom onset of the current episode within 90 days before enrollment.
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Individuals with a new acute or subacute episode of visual loss or visual dysfunction in one or both eyes, for whom optic neuritis is included in the initial differential diagnosis at participating clinical centers. Each participant contributes only one clinical episode to the primary diagnostic accuracy cohort.
Cohort
Prospective
Not listed
Diagnostic Performance of the 2022 International Criteria for Optic Neuritis
Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, with 95 percent confidence intervals, of the 2022 International Criteria for Optic Neuritis against Stage 2 full-information expert adjudication. Definite optic neuritis is index-positive and not optic neuritis is index-negative. Possible optic neuritis and indeterminate reference diagnoses are excluded from this conditional binary analysis and reported separately.
Diagnostic Yield of Definite Optic Neuritis Classification
Among participants with optic neuritis according to Stage 2 full-information expert adjudication, the proportion classified as definite optic neuritis by the 2022 International Criteria for Optic Neuritis. Possible optic neuritis and not optic neuritis classifications remain in the denominator.
Diagnostic Performance of the Antibody-Stratified Adjunct in Participants With Aquaporin-4 Immunoglobulin G Positivity or Clear-Positive Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Results
Among participants with aquaporin-4 immunoglobulin G positivity or clear-positive myelin oligodendrocyte glycoprotein immunoglobulin G results in the 3-month index window, diagnostic performance of the 2022 criteria alone and with the adjunct will be compared against Stage 2 full-information expert adjudication. Sensitivity, specificity, predictive values, and likelihood ratios with 95 percent confidence intervals will use the conditional and low-threshold definitions specified for the full-cohort comparison. Results will be reported for this subgroup overall and separately by antibody type. Definite-classification yield and reference diagnoses of newly upgraded cases will also be reported. Indeterminate reference diagnoses are excluded from binary accuracy calculations and reported separately.
Diagnostic Performance of the Low-Threshold 2022 Criteria Definition
Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, with 95 percent confidence intervals, when definite or possible optic neuritis is index-positive and not optic neuritis is index-negative under the 2022 criteria. Stage 2 full-information expert adjudication is the reference standard. Indeterminate reference diagnoses are excluded from binary accuracy calculations and reported separately.
Diagnostic Performance of the 2022 International Criteria for Optic Neuritis With the Antibody-Stratified Adjunct
In the full cohort, performance of the 2022 criteria with the adjunct will be compared with the original criteria against Stage 2 full-information expert adjudication. In the conditional analysis, definite optic neuritis is positive and not optic neuritis is negative; possible optic neuritis is excluded. In the low-threshold analysis, definite or possible optic neuritis is positive and not optic neuritis is negative. Sensitivity, specificity, predictive values, likelihood ratios, and 95 percent confidence intervals will be reported. Definite-classification yield will also be compared in the same reference-positive participants, retaining possible classifications as not definite. Reference diagnoses of newly upgraded cases will be reported. Indeterminate reference diagnoses are excluded from binary accuracy calculations but reported separately.
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