An observational study in Optic Neuritis, Optic Neuropathy and Visual Loss, sponsored by First Affiliated Hospital of Guangxi Medical University. Recruiting at 9 sites in China. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by First Affiliated Hospital of Guangxi Medical University · Observational
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.
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.
For each participant, two experts independently assess the case in two stages. In Stage 1, current and historical aquaporin-4 immunoglobulin G and myelin oligodendrocyte glycoprotein immunoglobulin G results, including directly revealing diagnostic labels, are withheld. Stage 1 judgments are recorded and locked before antibody disclosure. In Stage 2, the same experts reassess the case after receiving available antibody results and relevant assay information. Both stages use otherwise identical case information and the same information cutoff, no later than 6 months after enrollment. At each stage, cases are classified as optic neuritis, non-optic neuritis, or indeterminate. A third expert resolves disagreements under the corresponding information restrictions; Stage 1 disagreements are resolved before disclosure.
At both stages, experts are masked to the index classifications. Personnel assigning or verifying index classifications are masked to the expert reference diagnoses. Masking antibody results from experts does not remove those results from either index strategy. Index classifications and reference diagnoses are recorded separately and finalized before comparative analysis. Stage 2 full-information adjudication is the primary reference standard. Stage 1 provides a supplementary reference for sensitivity analyses and assessment of diagnostic changes after antibody disclosure. Initial agreement between experts is summarized at each stage using percentage agreement and Cohen's kappa.
The primary analysis treats definite optic neuritis as index-positive and not optic neuritis as index-negative; possible optic neuritis is excluded from this conditional binary analysis and reported separately. A secondary low-threshold analysis treats definite or possible optic neuritis as positive. Indeterminate reference diagnoses are excluded from the corresponding binary accuracy calculations but retained in reported category distributions. Definite-classification yield is also compared within the same reference-positive participants, retaining possible classifications as not definite. Newly upgraded cases are described according to their reference diagnoses. First-stage indeterminacy does not exclude a participant from second-stage analyses. Detailed outcome definitions are provided in the outcome measures section.
At initial public registration, recruitment was ongoing, and database lock, formal reference-standard adjudication, final index classification, and the primary diagnostic accuracy analysis had not occurred. The antibody-masked stage is an amendment-added assessment; full-information expert adjudication remains the primary reference standard.
88 studies on the registry are indexed under Optic Neuritis; 16 are open to participants now.
This study's planned enrollment of 500 is above the median of 150 across 25 observational studies indexed under Optic Neuritis.
Browse Optic Neuritis studies →First Affiliated Hospital of Guangxi Medical University is the lead sponsor of 41 studies on the registry; 25 are open to participants now.
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The criteria were revised on the registry on Sep 25, 2026. See what changed
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
1. The participant has previously been enrolled in this study. Each participant may be enrolled only once.
A history of optic neuritis or recurrent optic neuropathy before the current episode is not an exclusion criterion.
Individuals with acute or subacute visual loss or visual dysfunction in whom optic neuritis is included in the differential diagnosis at initial clinical assessment. Participants undergo routine clinical evaluation, with study data collected using a structured case report form. The 2022 International Criteria for Optic Neuritis are evaluated alone and with the antibody-stratified adjunct. No treatment is assigned by the study.
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.
Time frame: Index-test data within 3 months after symptom onset; reference-standard diagnosis up to 6 months after enrollment
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.
Time frame: Index-test data within 3 months after symptom onset; reference-standard diagnosis up to 6 months after enrollment
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.
Time frame: Index-test data within 3 months after symptom onset; reference-standard diagnosis up to 6 months after enrollment
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.
Time frame: Index-test data within 3 months after symptom onset; reference-standard diagnosis up to 6 months after enrollment
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.
Time frame: Index-test data within 3 months after symptom onset; reference-standard diagnosis up to 6 months after enrollment
Proportion of Indeterminate Reference-Standard Diagnoses
Proportion of participants assessed by the Stage 2 full-information expert adjudication panel whose reference-standard diagnosis is indeterminate.
Time frame: Up to 6 Months After Enrollment
Distribution of 2022 International Criteria for Optic Neuritis Classifications
Proportion of participants classified as definite optic neuritis, possible optic neuritis, or not optic neuritis by the 2022 International Criteria for Optic Neuritis.
Time frame: Baseline and diagnostic-window data for the current episode, within 3 months after symptom onset
Change in Expert-Adjudicated Diagnosis After Disclosure of Aquaporin-4 Immunoglobulin G and Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Results
Among participants with at least one aquaporin-4 immunoglobulin G or myelin oligodendrocyte glycoprotein immunoglobulin G result available within the reference-standard information window and completed adjudications at both stages, the proportion whose diagnosis changes after disclosure. The direction of change between optic neuritis, non-optic neuritis, and indeterminate diagnoses will be reported, overall and by antibody status. Participants with neither antibody result available, or with an adjudication missing at either stage, are excluded from this proportion and reported separately. Diagnostic change is not assumed to represent correction of an error.
Time frame: Paired adjudications using baseline and follow-up information available up to 6 months after enrollment
Plan to share: Yes — De-identified participant-level data and a data dictionary will be made available to qualified researchers upon reasonable request after publication of the main diagnostic accuracy results, subject to ethics approval, institutional approval, and execution of a data use agreement.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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First Affiliated Hospital of Guangxi Medical University