Retinal ganglion cell loss is associated with multimodal visual dysfunction following demyelinating optic neuritis

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Background Optic neuritis (ON) is a common manifestation of multiple sclerosis and related disorders (MSRD) characterized by retinal neurodegeneration, including thinning of ganglion cell-inner plexiform layer (GCIPL). Compared to absolute values, inter-eye differences (IED) account for variation in baseline structure and function before ON. Objectives To determine retinal layer IED thresholds associated with multimodal visual dysfunction after unilateral demyelinating ON. Methods In this cross-sectional study, MSRD participants with and without a history of unilateral ON, and healthy controls underwent optical coherence tomography, best-corrected visual acuity, 2.5% and 1.25% low-contrast letter acuity (LCLA), standard automated perimetry, and color vision testing. Results Sixty-six participants with MSRD (33 with unilateral ON history, 33 without ON history) and 15 healthy controls were included. For the ON cohort, a GCIPL IED threshold of 6.5% was associated with dyschromatopsia (AUC = 0.76, p = 0.011), 11% with 1.25% LCLA IED of >5 letters (AUC = 0.75, p = 0.008), 13% with 2.5% LCLA IED of >5 letters (AUC = 0.86, p < 0.001), 15% with VFMD IED of >2 dB (AUC = 0.75, p = 0.031), and 27% with logarithm of minimum angle of resolution IED of >0.3 (AUC = 1.00, p < 0.001). These associations were more robust compared to other retinal layer IED. Conclusions GCIPL IED thresholds more accurately reflect multimodal visual dysfunction after ON compared to other retinal layer IED.