Validation of inter-eye difference thresholds in optical coherence tomography for identification of optic neuritis in multiple sclerosis

Objective: To examine and validate thresholds for inter-eye differences in peripapillary retinal nerve fibre (pRNFL) and ganglion cell + inner plexiform layer (GCIPL) thicknesses for identifying unilateral optic neuritis in MS. Methods: In this two-centre, cross-sectional study, optical coherence tomography was performed in 340 patients with clinically isolated syndrome (CIS) and MS. Cut-off values of inter-eye difference for identification of eyes with a history of unilateral ON were evaluated by receiver-operating characteristics analysis. Results: For pRNFL >= 5 mu m sensitivity was 69% and specificity 68%, while for GCIPL >= 4 mu m sensitivity was 67% and specificity 78%. The areas under the curve (AUC) were 0.72 (95% confidence interval: 0.64 - 0.79) for pRNFL and 0.78 (95%CI: 0.72 - 0.85) for GCIPL, indicating GCIPL as the superior model (p < 0.001). When analysing only CIS patients, GCIPL inter-eye difference >= 4 mu m also remained significant, while pRNFL inter-eye difference did not. Interpretations: Inter-eye differences of >= 4 mu m for GCIPL and to a lesser degree >= 5 mu m for RNFL are robust thresholds for identifying unilateral optic nerve lesions. These thresholds could be used to demonstrate previous symptomatic and possibly asymptomatic ON and might be included into a new version of the diagnostic criteria.