Differentiation of acute-phase AQP4-IgG+ optic neuritis from CNS inflammatory diseases using optic nerve head blood flow analysis

Early diagnosis of optic neuritis (ON) associated with aquaporin-4 immunoglobulin-G (AQP4-IgG), myelin oligodendrocyte glycoprotein immunoglobulin-G (MOG-IgG), or multiple sclerosis (MS) is challenging due to invasive and time-consuming tests. We investigated whether ophthalmologic assessments, including laser speckle flowgraphy (LSFG) and optical coherence tomography (OCT), are useful for distinguishing among these diseases at ON onset. This retrospective study included 10 AQP4-IgG+ON patients, 20 MOG-IgG+ON patients, 9 MS-ON patients, and 27 idiopathic ON (ION) patients at initial onset, and 66 propensity-score-matched control eyes. We measured mean blur rate (MBR), representing blood flow velocity, using LSFG and assessed optic nerve head (ONH) vessel-area MBR (ONH-MV), tissue-area MBR (ONH-MT), and peripapillary choroidal MBR. Circumpapillary retinal nerve fiber layer (cpRNFL) thickness was measured with OCT. We found that MOG-IgG+ON patients had a significantly thicker cpRNFL than AQP4-IgG+ON patients and controls (P < 0.05). AQP4-IgG+ON and MOG-IgG+ON patients had significantly lower ONH-MV than controls (P ≤ 0.001). AQP4-IgG+ON patients had significantly lower ONH-MT than MOG-IgG+ON, MS-ON, ION patients, or controls, and lower choroidal MBR than controls (P < 0.05). A receiver operating characteristic analysis combining cpRNFL thickness, ONH-MV, ONH-MT, and choroidal MBR achieved an area under the curve of 0.892 in differentiating AQP4-IgG+ON from other diseases (P < 0.001). LSFG and OCT could distinguish AQP4-IgG+ON from other diseases at onset non-invasively.