Abstract
BACKGROUND AND OBJECTIVES: Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS), aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Compared with MS-ON, AQP4-ON and MOGAD-ON eyes exhibit more severe thinning of the macular composite ganglion cell + inner plexiform layer (GCIPL), as measured by optical coherence tomography (OCT). The individual measurement of the ganglion cell (GCL) and inner plexiform (IPL) layers, typically assessed together as the composite GCIPL thickness, has remained largely unexplored. In this study, we aimed to examine the relative contribution of GCL and IPL thinning to overall GCIPL thinning in MS-ON, AQP4-ON, and MOGAD-ON eyes. METHODS: For the cross-sectional analysis, MS, AQP4+NMOSD, and MOGAD participants with a history of ON >6 months prior and healthy controls (HC) underwent retinal imaging. For the longitudinal analysis, the evolution of GCL and IPL thinning was examined in people with baseline OCT within 30 days of a first episode of acute ON. RESULTS: In the cross-sectional cohort, GCL and IPL volumes were lower in AQP4-ON (n = 30 eyes) and MOGAD-ON (n = 47 eyes), as compared with MS-ON (n = 66 eyes), but did not differ between AQP4-ON and MOGAD-ON eyes. The GCL/GCIPL ratio was lower in ON eyes relative to HC and was correlated with GCIPL volume, with a similar pattern across disease groups. AQP4-ON and MOGAD-ON eyes had a lower GCL/GCIPL ratio compared with MS-ON, with no significant difference between AQP4-ON and MOGAD-ON. In the longitudinal cohort, the GCL/GCIPL ratio was already reduced in the ON eyes (n = 19 eyes) compared with the fellow non-ON eyes at the baseline scan within the first month from ON (-1.01% [-1.59% to -0.44%], p = 0.002). A greater loss of GCIPL volume after acute ON was associated with a greater decrease of the GCL/GCIPL ratio (r = 0.50, p < 0.001). DISCUSSION: More severe GCIPL thinning after ON was associated with a lower GCL/GCIPL ratio, supporting that more GCL than IPL thinning occurs after ON. The pattern was similar across neuroinflammatory conditions including MS, MOGAD, and AQP4+NMOSD. Our findings may help shed light into dynamics of inner retinal layer atrophy after ON.