A clinical entity of IgG4-related ophthalmic disease (IgG4-ROD) was identified in 2004 as the first report of IgG4-related Mikulicz disease. In cases with IgG4-ROD, enlargements of the extraocular muscles and the trigeminal nerves were also often noted. The most important condition identified in differential diagnosis of this disease is orbital MALT lymphoma: it is noteworthy that IgG4-ROD and MALT lymphoma can coexist occasionally. The most important issue in the management of IgG4-ROD is care and attention for optic neuropathy. The findings of previous studies and our experience suggest that almost 10% of IgG4-ROD cases could show optic neuropathy. In the worst case in our institute, the patient's visual acuity decreased to no light perception. Attention should be paid to the onset of optic neuropathy in patients that do not receive steroid therapy, especially when the serum IgG4 level is high. An early stage of IgG4-related optic neuropathy could be misdiagnosed as glaucoma. Although visual function in these patients responded to steroid therapies, their recoveries were limited; therefore, early detection and treatment is desired.

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This article relates to a lecture that was delivered on November 6 and 7, 2015 at the 53^rd annual meeting of the Japanese Neuro-ophthalmology Society. Our study revealed the following clinical characteristics of anti-aquaporin-4 antibody-positive optic neuritis: poor visual prognosis, frequent recurrence, and high autoantibody positivity rates. Although about 60% of the patients treated using steroid pulse therapy had a poor visual outcome, the remaining 40% of patients had a better visual outcome. These results indicate that clinicians should treat anti-aquaporin-4 antibody-positive optic neuritis; not only to improve visual function in the acute phase, but also to prevent recurrence in the chronic phase. However, one problem that must be overcome is that it is difficult to assess the effects of various treatments for anti-aquaporin-4 antibody-positive optic neuritis, because the disease has a low incidence and widely varied visual prognoses.

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Optical treatment using membrane press-on prisms is employed in many patients with diplopia. However, remnant diplopia in peripheral gaze directions is an important issue after ordinal optical treatment. We set 3 goals: achieving binocular vision, eliminating diplopia in all gaze directions, and obtaining peripheral visual fields. In accordance with our procedure, which we named the S-S method, prism spectacles, followed by partial peripheral occlusions and a spot patch using Bangerter occlusion foils, were adopted in our hospital. The number of prism prescription angles was found to reduce when partial occlusions were used. Moreover, single vision using only partial occlusions without prism spectacles was achieved in 16% (34 out of 213) patients with diplopia. We introduced the S-S method and its principles for eliminating diplopia in peripheral gaze directions by using partial occlusions and reported the results of our method.

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An increase in incidence of cases of elderly patients with myasthenia gravis (MG) has been reported. Thus, we analyzed age-specific incidence of MG at Osaka Medical College over the past 7.5 years. Titers of acetylcholine receptor (AChR) antibodies were also measured. Additionally, 5 cases of patients with ocular myasthenia who developed their symptoms after 65 years of age were treated with low-dose corticosteroids (10 mg prednisolone, daily). We diagnosed 23 cases with MG during that interval. Of those cases, 10 cases (43%) were patients ＞65 years of age. Acetylcholine receptor antibody was positive in 61.5% of cases with patients ＜65 years of age, whereas AChR was positive in 80% of cases with patients \>65 years of age. Low-dose corticosteroid therapy was effective in elderly patients with ocular MG; their diplopia disappeared approximately 2 months later. All cases led to pharmacologic remission (mean, 7.5 months). Therefore, we conclude that incidence of elderly patients diagnosed with MG is not rare. We also suggest that patient response to low-dose corticosteroid therapy was relatively positive and it should be considered when determining initial dosage of corticosteroids for elderly patients with ocular myasthenia.

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Herein, we report a case of a 17-year-old boy with Noonan syndrome diagnosed with Miller Fisher syndrome. He presented with photophobia associated with the preceding symptom of gastroenteritis. Subsequently, the patient exhibited symptoms of dysesthesia. Afterward, he underwent a check-up at our hospital's Department of Pediatrics where he presented with ataxia and areflexia. Mydriasis was recognized along with disappearance of light reflexes and omnidirectional external ophthalmoplegia. The patient was diagnosed with Miller Fisher syndrome; serum anti-GQ1b IgG was positive. The patient did not receive therapy and his symptoms resolved spontaneously. It was discovered that he closed his eyes due to photophobia and mental retardation. Patients with Noonan syndrome have eye complications; however, it is difficult to perform a medical examination because of mental retardation.

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Five cases of myasthenia gravis associated with thymoma were reported clinicopathologically, radiologically, and serologically. Patients were > 63 years of age (mean; 69 years) and 4 patients were diagnosed with ocular myasthenia while 1 patient was diagnosed with generalized myasthenia. All patients had anti-acetylcholine receptor antibodies, some autoantibodies against titin or interferon α, and no anti-muscle-specific tyrosine kinase (MuSK) antibodies. Computed tomography scans showed soft shadows inside anterior mediastinum in 4 of 5 patients and tuberculous shadow in 1 patient. Positron emission tomography showed abnormal accumulation in all 3 patients it was performed on. Using the World Health Organization (WHO) classification, 2 patients were classified as type AB and 1 patient was classified as type B3; there was also 1 diagnosis of thymic cyst.

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Optical coherence tomography (OCT) angiography is a new, noninvasive technique for estimating retinochoroidal circulation that does not require injection of any exogenous dye or contrast agent. Herein, we report a case of anterior ischemic optic neuropathy (AION) diagnosed using OCT angiography. A 52-year-old woman visited our hospital complaining of upper temporal visual field loss in her left eye. She had normal visual acuity in both eyes. The optic nerve head in her left eye revealed hyperemia and swelling, and dye leakage was observed inferiorly on fluorescein angiography. On OCT angiography, radial peripapillary capillaries were not visualized and a diagnosis of AION was made. No treatment was provided as her visual acuity had not decreased. Ten days later, reconstruction of vascular networks of superficial discs was recognized on OCT angiography. Optical coherence tomography angiography can be useful for diagnosis and follow-up of patients with AION.

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The retina is isolated and protected from the systemic circulation by the blood retinal barrier. This barrier is supported by retinal blood vessels and the perivascular neurons and glia, forming a neurovascular unit (NVU). Recent studies have suggested that a breakdown of the NVU is associated with various retinal diseases, and the NVU has attracted much research interest. In addition, a new treatment concept of neurovascular protection, aiming to protect the integrity of the NVU, has emerged and is expected to be developed for elucidating the pathogenesis of various retinal diseases and developing new treatment modalities for them.

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Fisher syndrome (FS) is a regional variant of Guillain-Barré syndrome (GBS) and is characterized by three clinical symptoms, i.e., ophthalmoplegia, ataxia, and areflexia, which are known as the FS triad. In 1956, Miller Fisher was the first to report a detailed clinical description of the characteristics of this syndrome. The pathological mechanisms and nosology of the syndrome have been discussed for several decades, but the arguments lacked a disease-specific biomarker. Further research on anti-glycolipid antibodies related to GBS that began in the late 1980s led to the discovery of a disease-specific biomarker, an immunoglobulin G (IgG) antibody against ganglioside GQ1b, in FS. An anti-GQ1b antibody-related animal model of FS has not yet been established; however, the pathological significance of the anti-GQ1b antibody has been strongly suggested based on the following findings: high incidence and disease-specificity of the antibody; increase in the antibody titers before neurological onset; unique distribution of the GQ1b-antigen consistent with the clinical characteristics of FS in human peripheral nervous tissues; and the presence of GQ1b-mimicking oligosaccharide structures in causative organisms of preceding infection. Serum IgG antibodies against ganglioside GQ1b have also been detected in other conditions with clinical characteristics similar to FS, such as GBS with ophthalmoplegia, acute ophthalmoplegia, ataxia following an infection, and atypical cases with central nervous system manifestations. Therefore, these antibodies are considered to be important diagnostic biomarkers for FS and other related conditions.

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We report a 43-year-old man who developed pure acquired downbeat nystagmus with increasing velocity slow phase. This downbeat nystagmus continuously appeared at vertical eye positions of ±20°, while showing nystagmus intensity-vertical eye position relationship contra to Alexander's law. The patient had ischemic lesions at the left caudal paravermis-hemisphere following acute bacterial mengitis that included the paraflocculus. Simulation analysis showed that slow phase position curves of the nystagmus were approximated by both exponential and quadratic curves with a high correlation coefficient. However, differential curves were close to a linear slope rather than an exponential one. There was a linear correlation between vertical eye position and maximum velocity (p<0.01) of slow phase. The neutral point obtained from the regression line was down 32.6°which was extremely shifted from the primary position. GABAergic agonists were applied orally to evaluate their effects on the nystagmus. We found that clonazepam combined with gabapentin significantly reduced maximum slow phase velocity and the neutral point obtained from the regression line was shifted to down 18.6°. Furthermore, increasing velocity slow phase of downbeat nystagmus changed to linear upward drift in waveform during fixation at the primary to down positions. The present study indicates that our acquired downbeat nystagmus with increasing velocity slow phase resulted from the deficit of inhibitory input from the paraflocculus to the vestibular nuclei and would coexist with vestibular upward drift.

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