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Purpose: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. Design: Multicenter cross-sectional, observational cohort study. Participants: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. Methods: Serum samples from patients with optic neuritis were tested for antieaquaporin-4 antibodies (AQP4-Abs) and antiemyelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. Main Outcome Measures: Antibody positivity, clinical and radiologic characteristics, and visual outcome. Results: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Abepositive group), median VA improved to 0.4 logMAR in the AQP4-Abepositive group, 0 logMAR in the MOG-Abepositive group, and 0.1 logMAR in the double-negative group. The AQP4-Abepositive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Abepositive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Abepositive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. Conclusions: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Antieaquaporin-4 antibodyepositive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.

In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.

BackgroundLeber hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy that leads to central loss of vision, predominantly in young males. Most LHON cases have one of three primary point mutations in mitochondrial DNA (mtDNA). The annual incidence and prevalence of LHON in Japan are not known. Thus, we estimated the annual incidence of molecularly confirmed LHON in Japan during 2014.MethodsSequential questionnaires were sent to 1397 facilities, which included all of the university hospitals in Japan, and they were certified by either the Japanese Ophthalmological Society or the Japanese Neuro-Ophthalmological Society. We calculated the incidence number (Ir) as the number of patients who developed LHON in 2014 and its 95% confidence interval.ResultsWe received 861 responses to the first questionnaire, where 49 facilities reported 72 cases (67 were male and 5 were female) of newly developed LHON during 2014. Ir was calculated as 117, and the 95% confidence interval ranged from 81 to 153. For the second questionnaire, responses were received from 30 facilities, where the median age at onset was 38 years for males and 30 years for females, and 86.5% of cases possessed the mtDNA ND4/G11778A mutation.ConclusionApproximately 120 cases of newly developed LHON were reported during 2014 in Japan, and 93.2% were males.

Malignant lymphoma by far was found to have the most dramatic increases within the recent reported series. Pleomorphic adenomas in Japan were found to be much more common compared with that reported for American and European studies.