Background and objective: Chronic relapsing inflammatory optic neuritis (CRION) is one of the more common phenotypes related to myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). The absence of specific biomarkers makes distinguishing between CRION and relapsing inflammatory ON (RION) difficult. A recent work has suggested a widespread affectation of the central nervous system in CRION patients. In order to search for a potential CRION marker we have measured brain atrophy in a cohort of patients, stratified by phenotypes: CRION, RION, multiple sclerosis with a history of optic neuritis (MS-ON), and MOG-Abs status.Methods: A cross-sectional study was conducted in 31 patients (seven CRION, 11 RION, and 13 MS-ON). All patients were tested for MOG and aquaporin-4 antibodies (AQ4-Abs). Clinical data were collected. Brain atrophy was calculated by measuring the brain parenchyma fraction (BPF) with Neuroquant® software.Results: Four of seven CRION patients and one of 11 RION patients were positive for MOG-Abs (p = 0.046) and no MS-ON patients tested positive to MOG-Abs. All patients were negative to AQ4-Abs. The BPF was lower in patients with CRION than patients with RION (70.6 vs. 75.3%, p = 0.019) and similar to that in MS-ON patients.Conclusions: Brain atrophy in idiopathic inflammatory relapsing ON is present in patients with the CRION phenotype. Data from this study reflect that the optic nerve is a main target involved in these patients but not the only one. Our results should be further investigated in comprehensive and prospective studies.