Neurofilament light chain levels differentiate ischemic from inflammatory optic neuropathies

Background: Serum neurofilament light chain (sNfL) levels may be useful for differentiating non-arteritic anterior ischemic optic neuropathy (NAION) and optic neuritis (ON). The purpose of the study is to determine the discriminatory capacity of sNfL in NAION versus aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) ON, and to evaluate if sNfL levels at attack correlate with visual outcomes. Methods: We evaluated sNfL levels (pg/mL) in patients with acute, isolated, unilateral or bilateral optic neuropathy with AQP4-IgG or MOG-IgG positive ON and NAION and serum samples of 24 unaffected controls. Results: Thirteen AQP4-IgG+NMOSD, 13 MOGAD, 15 NAION, and 24 unaffected controls were included. sNfL levels differed between all cohorts (AQP4-IgG+NMOSD: 10.1 [IQR] 8.9-24.4]), MOGAD: 16.0 [IQR 10.5-24.2]; NAION: 36.9 [IQR 20.5-69.5]; unaffected controls: 6.5 [IQR 5.5-9.6]; p < 0.001). There was a difference in sNfL levels between ON and NAION (median 11.6 [IQR 9.3-24.4] versus 36.9 [IQR 20.5-69.5], p < 0.001). Serum Nfl of 60 pg/mL (Youden's index = 0.49; AUC = 0.82) provided sensitivity of 33 % and 100 % specificity when discriminating NAION from ON. Serum NfL levels were correlated with final visual acuity after adjusting for optic neuropathy etiology (model R2 0.49; p < 0.001). Discussion: sNfL levels may aid in discriminating between NAION and acute ON associated with AQP4-IgG+NMOSD and MOGAD and may predict long-term visual outcomes. However, results should be interpreted with caution as further studies are required using standardized z-scores in place of raw sNfL levels.