A Multicenter Prospective Diagnostic Accuracy Study of the 2022 International Criteria for Optic Neuritis and an Antibody-Stratified Adjunct in Acute or Subacute Visual Loss When Optic Neuritis Is Suspected in China

This multicenter prospective observational study evaluates the 2022 International Criteria for Optic Neuritis, alone and with an antibody-stratified adjunct, in patients initially suspected of having optic neuritis. Structured prospective data collection began on January 6, 2025. Each participant contributes one clinical episode. The cohort is not restricted to participants ultimately diagnosed with optic neuritis. Diagnostic testing and treatment are determined by the treating clinicians as part of routine care.

Baseline symptoms and ophthalmic findings are recorded using a structured electronic case report form. Available visual field, optical coherence tomography, magnetic resonance imaging, and laboratory findings are collected. Baseline and follow-up optical coherence tomography are encouraged when clinically feasible but are not required by study participation. Available follow-up findings can support reference-standard adjudication. Absence of follow-up optical coherence tomography alone does not exclude a participant from the primary analysis.

Both index strategies use baseline clinical data and eligible paraclinical information obtained within 3 months after symptom onset for the current episode, based on examination or sample collection dates. Later information will not revise either index classification. The 2022 criteria assign definite optic neuritis, possible optic neuritis, or not optic neuritis using prospectively recorded clinical findings, including actual color vision assessments rather than assumed abnormalities.

The antibody-stratified adjunct described in Table 2 of Liang and colleagues (2026) is applied only to participants with aquaporin-4 immunoglobulin G positivity or clear-positive myelin oligodendrocyte glycoprotein immunoglobulin G results in the index window. Under that framework, acute or subacute visual loss with at least one objective finding consistent with optic neuropathy supports definite optic neuritis; without such an objective finding, the adjunct category is possible optic neuritis. The final index classification is the higher-certainty category assigned by the 2022 criteria or the adjunct, using the hierarchy definite optic neuritis, possible optic neuritis, then not optic neuritis. Participants without either qualifying positive antibody result retain their original 2022 criteria classification. Unavailable antibody results are not treated as negative.

Participants are followed for up to 6 months after enrollment whenever feasible. Reference-standard adjudication uses baseline information and available clinical course, repeat examinations, investigations, treatment response, and alternative diagnoses within this period. The target is whether the current episode represents optic neuritis, not merely whether an antibody-associated disease is present.