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 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 optic nerve-related 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.
None
Individuals with a new acute or subacute episode of visual loss or optic nerve-related 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, predictive values, likelihood ratios, and 95 percent confidence intervals will be assessed against the expert-adjudicated reference standard. Definite optic neuritis will be index-test positive and not optic neuritis will be index-test negative. Possible optic neuritis will be treated as an indeterminate index-test category and reported separately. Indeterminate reference-standard diagnoses will be excluded. Index-test classification will use eligible baseline and paraclinical data obtained within 3 months after symptom onset; later follow-up data will not revise the index-test classification.
Diagnostic Yield of Definite Optic Neuritis Classification
Proportion of participants with expert-adjudicated optic neuritis who are classified as definite optic neuritis by the 2022 International Criteria for Optic Neuritis.
Diagnostic Performance of the Antibody-Stratified Adjunct in Adjunct-Qualifying Antibody-Positive Participants
Diagnostic performance of the prespecified antibody-stratified adjunct will be evaluated among participants with aquaporin-4 immunoglobulin G positivity or clear-positive myelin oligodendrocyte glycoprotein immunoglobulin G. Under this adjunct, qualifying antibody-positive cases with objective optic nerve evidence will be classified as definite optic neuritis and compared with the expert-adjudicated reference standard. Diagnostic performance will be assessed overall in adjunct-qualifying antibody-positive participants and separately in the aquaporin-4 immunoglobulin G-positive and clear-positive myelin oligodendrocyte glycoprotein immunoglobulin G subgroups. Participants with an indeterminate reference-standard diagnosis will be excluded from this binary diagnostic accuracy analysis.
Diagnostic Performance of the Low-Threshold 2022 Criteria Definition
Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, and 95 percent confidence intervals when definite optic neuritis or possible optic neuritis is classified as index-test positive and not optic neuritis is classified as index-test negative.
Diagnostic Performance of the 2022 International Criteria for Optic Neuritis With the Antibody-Stratified Adjunct
The antibody-stratified adjunct will be applied in combination with the 2022 International Criteria for Optic Neuritis, rather than as a standalone diagnostic test. Diagnostic performance of the combined criteria-plus-adjunct classification will be assessed against the expert-adjudicated reference standard. Participants with an indeterminate reference-standard diagnosis will be excluded from this binary diagnostic accuracy analysis.
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