Hyperactivity of the medial thalamus in patients with photophobia-associated migraine.

OBJECTIVE: To examine cerebral functional alterations associated with sensory processing in patients with migraine and constant photophobia. BACKGROUND: Migraine is a common headache disorder that presents with photophobia in many patients during attacks. Furthermore, some patients with migraine experience constant photophobia, even during headache-free intervals, leading to a compromised quality of life. METHODS: This prospective, case-control study included 40 patients with migraine (18 male and 22 female) who were recruited at an eye hospital and eye clinic. The patients were divided into two groups: migraine with photophobia group, consisting of 22 patients (10 male and 12 female) with constant photophobia, and migraine without photophobia group, consisting of 18 patients (eight male and 10 female) without constant photophobia. We used 18F-fluorodeoxyglucose and positron emission tomography to compare cerebral glucose metabolism between the two patient groups and 42 healthy participants (16 men and 26 women). RESULTS: Compared with the healthy group, both the migraine with photophobia and migraine without photophobia groups showed cerebral glucose hypermetabolism in the bilateral thalamus (p < 0.05, family-wise error-corrected). Moreover, the contrast of migraine with photophobia minus migraine without photophobia patients showed glucose hypermetabolism in the bilateral medial thalamus (p < 0.05, family-wise error-corrected). CONCLUSIONS: The medial thalamus may be associated with the development of continuous photophobia in patients with migraine.

Clinical Features and Prognostic Factors in Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis.

In order to review the clinical features of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis (MOGON), we investigated the clinical characteristics, visual function, optical coherence tomography findings, and magnetic resonance imaging of 31 patients (44 eyes). MOGON was more common in middle age without sex difference and was characterised by pain on eye movement and optic disc swelling. Magnetic resonance imaging lesions tended to be long with inflammation around the optic nerve sheath; longer lesions were associated with worse visual acuities at onset. Recurrence was significantly associated with retinal nerve fibre layer thinning, and thus, it is important to reduce recurrence as much as possible.

A Japanese Case of Leber's Hereditary Optic Neuropathy with the m.13051G>A Pathogenic Variant.

Leber's hereditary optic neuropathy (LHON) is one of the hereditary optic neuropathies and is principally caused by three frequent mitochondria deoxyribonucleic acid (DNA) pathogenic variants (m.11778 G>A, m.3460 G>A, and m.14484T>C). These pathogenic variants account for 90% of LHON cases, with rare pathogenic variants accounting for the remaining cases. We report the first Japanese case of LHON with the m.13051 G>A pathogenic variant, which is a rare primary pathogenic variant of LHON. A 24-year-old woman developed subacute visual loss in both eyes over several months. The best corrected visual acuity (BCVA) was 6/120 in her right eye (OD) and 6/7.5 in her left eye (OS). A relative afferent pupillary defect was not detected. Humphrey visual field testing revealed a central scotoma OD and a temporal paracentral scotoma OS. Fundus examination showed the presence of a pale optic disc OD and optic disc swelling with peripapillary microangiopathy OS. Orbital magnetic resonance imaging showed no abnormal findings. As the mitochondrial DNA gene testing demonstrated the m.13051 G>A pathogenic variant, the patient was diagnosed with LHON. Subsequently, her BCVA worsened to 6/600 in each eye, followed by a nearly plateau-like progression thereafter. This mutation has been primarily reported in Europe but has not yet been confirmed in the Asian region. This case also indicates the importance of examining the whole mitochondrial DNA gene for pathogenic variants in cases where one of the three major pathogenic variants has not been not detected.

Clinical Features of Crowded Orbital Syndrome on Magnetic Resonance Imaging.

We have previously reported strabismus due to mismatch of orbital volume and globe as 'crowded orbital syndrome' (COS). In this study we have used magnetic resonance imaging (MRI) to investigate its clinical features. This has revealed that a globe with a similar axis occupies a larger volume in the orbit in patients with COS than in controls without strabismus. This suggests that strabismus with high myopia may easily occur in those with relatively small orbits and axial elongation. In acquired esotropia and/or vertical strabismus, a mismatch of orbital volume and globe axis should be investigated with MRI.

Clinical Characteristics of Anti-aquaporin 4 Antibody Positive Optic Neuritis in Japan.

To investigate the clinical characteristics and the effectiveness of maintenance therapy of anti-AQP4 antibody positive optic neuritis in Japanese patients, medical records from 69 patients (103 eyes) were retrospective reviewed. The status of relapse in patients who received maintenance therapy following acute therapy was compared with that before maintenance therapy in patients who started maintenance therapy ≥6 months after acute therapy. In Japan, anti-AQP4 antibody positive optic neuritis was characterized by older onset age and poor visual outcome. The yearly rate and total number of relapses were lower when maintenance therapy was followed immediately after acute therapy.

Nationwide epidemiological survey of Leber hereditary optic neuropathy in Japan.

BACKGROUND: Leber 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. METHODS: Sequential 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. RESULTS: We 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. CONCLUSION: Approximately 120 cases of newly developed LHON were reported during 2014 in Japan, and 93.2% were males.

Visual prognosis better in eyes with less severe reduction of visual acuity one year after onset of Leber hereditary optic neuropathy caused by the 11,778 mutation.

BACKGROUND: Patients with Leber hereditary optic neuropathy (LHON) have a progressive decrease of their visual acuity which can deteriorate to <0.1. Some patients can have a partial recovery of their vision in one or both eyes. One prognostic factor associated with a recovery of vision is an early-age onset. The purpose of this study was to determine other clinical factors that are predictive of a good visual recovery. METHODS: Sixty-one Japanese LHON patients, with the 11,778 mutation and a mean age of 23.1 ± 12.1 years at the onset, were studied. All patients were initially examined at an acute stage of LHON and were followed for 3 to 10 years. At 1 year after the onset, the lowest visual acuity was <0.1 in all eyes. We studied the following parameters of patients with/without a final visual acuity of ≥ 0.2: sex; heavy consumption of cigarettes and alcohol; taking idebenone; mean age at onset; mean lowest visual acuity; and distribution of the lowest and the final visual acuity. RESULTS: Fifteen (24.6%) of the 61 patients or 25 (20.5%) of the 122 eyes had a recovery of their visual acuity to ≥ 0.2. The mean age at onset of these 15 patients with visual recovery to ≥ 0.2 was 17.5 ± 7.7 years, and that of the 46 patients without visual recovery to ≥ 0.2 was 25.0 ± 12.8 years (P = 0.02, Mann-Whitney U test). The mean lowest visual acuity of the 25 eyes with visual recovery ≥ 0.2 was 0.04, and that of the 97 eyes without visual recovery to ≥ 0.2 was 0.015 (P < 0.001, Mann-Whitney U test). Fifty percent (15/30) of the eyes whose lowest visual acuity was ≥ 0.04 during 1 year after the onset had a visual recovery to ≥ 0.2, while 11% (10/92) of the eyes whose the lowest visual acuity was ≤ 0.03 had a visual recovery to ≥ 0.2 (P < 0.001, χ 2 test). There were no significant differences in the other clinical factors. CONCLUSION: A final visual acuity of ≥ 0.2 was associated with a less severe reduction of the visual acuity at 1 year after the onset. Our findings can be used to predict the visual prognosis in LHON patients.

[Designation criteria for Leber's hereditary optic neuropathy].

Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.

Anti-NMDA receptor encephalitis associated with transient cerebral dyschromatopsia, prosopagnosia, and lack of stereopsis.

A 20-year-old woman suffered from anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and was treated with removal of an ovarian teratoma and retroperitoneal ganglioneuroma in addition to immunotherapy. She was incapable of face recognition, had difficulty with object recognition, and lacked color sensation and stereo perception during recovery. These symptoms were transient and completely resolved over 4 months. Our report documents additional aspects of visual impairment associated with anti-NMDAR encephalitis and suggests that the disease can lead to diffuse cerebral dysfunction including the cortical visual system.

Evaluation of Steroid Pulse Therapy Responsiveness in Myelin-Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis.

PURPOSE: Myelin-oligodendrocyte glycoprotein antibody-positive optic neuritis (MOGON) is usually responsive to the steroid, but, for some patients, steroid pulse therapy alone may be inadequate. This study aimed to investigate the factors predicting the response to steroid pulse therapy in MOGON. METHODS: This study included 17 patients (24 eyes) with MOGON, who received single steroid pulse therapy as initial treatment. Best corrected visual acuity (BCVA) and mean deviation (MD) values after treatment were examined concerning findings at onset. RESULTS: No correlation was found between BCVA at onset and after treatment, but a correlation was observed between MD values at onset and after treatment (correlation coefficient 0.48, p=0.01, Spearman's rank correlation coefficient). Age, gender, duration from onset to treatment, magnetic resonance imaging findings, and optical coherence tomography findings did not affect visual function after treatment. CONCLUSIONS: Severe visual field impairment at onset may indicate that additional treatment may be necessary.

A Case of Herpes Zoster Ophthalmicus With Multiple Delayed Ocular Complications.

Herpes zoster ophthalmicus (HZO) presents a variety of ocular complications, most of which occur simultaneously as skin lesions. We report a case of HZO with delayed onset of multiple ocular complications. A 72-year-old man developed HZO, blepharitis, iritis, and conjunctivitis in the left eye, which resolved after topical ocular treatment and systemic acyclovir administration. However, six weeks after the first onset of the rash, the patient came to our hospital because of recurrent blepharitis, iritis, scleritis, conjunctivitis, eye pain, ptosis, and blurred vision in the left eye. Best corrected visual acuity (BCVA) in the left eye had decreased to hand motion, and the Goldmann visual field test showed only mild residual peripheral vision on the lateral side. Intraocular pressure showed 25 mmHg in the left eye and inflammation in the anterior chamber with paralytic mydriasis. Orbital magnetic resonance imaging (MRI) showed the contrast effects with the lacrimal gland, superior ophthalmic vein, supraorbital nerve, optic nerve, and around optic nerve sheath. The patient was diagnosed with optic neuritis, optic perineuritis, ptosis, paralytic mydriasis, trigeminal neuralgia, lacrimal gland inflammation, blepharitis, iritis, scleritis, and ocular hypertension after HZO, and three courses of steroid pulse therapy were administered. Thereafter, BCVA improved to 0.3 in the left eye, with improvement in central vision, and MRI lesions and other symptoms also improved. The patient has had no complications or recurrence of HZO. HZO can cause a variety of ocular complications. Since autoimmune mechanisms might be involved, combined immunotherapy should be considered.

Glucose hypermetabolism in the thalamus of patients with hemifacial spasm.

The purpose of this study was investigate functional alteration in the brains of patients with hemifacial spasm using positron emission tomography (PET). We studied cerebral glucose metabolism using PET with (18) F-fluorodeoxyglucose in 13 patients with right lateral hemifacial spasm and 13 with left lateral hemifacial spasm. All patients underwent 2 PET scans before treatment (active state) and after treatment (suppressive state) with the botulinum neurotoxin type A. At the time of the PET scans, the severity of the spasm was rated according to the Jankovic Disability Rating Scale. We also used magnetic resonance imaging to evaluate the grade of neurovascular compression in each patient using scores of 1 to 3 (1 = mild, 3 = severe). Fifty-two normal volunteers were examined as controls. Compared with controls, patients with right and left hemifacial spasm showed bilateral cerebral glucose hypermetabolism in the thalamus in both the active and suppressive states. However, thalamic glucose metabolism after the suppressive state was significantly reduced compared with that in the active state using region of interest analysis. There was a positive correlation between the severity of the spasm in the active state and the score of neurovascular compression (rs = 0.65) that was estimated using Spearman order correlation coefficient. We observed bilateral cerebral glucose hypermetabolism in the thalamus of patients with hemifacial spasm. The thalamic glucose hypermetabolism may be attributed to multiple sources, including afferent input from the skin and muscle spindle, antidromic conduction of the facial nerve, and secondary alteration in the central nervous system.

Gray matter density increase in the primary sensorimotor cortex in long-term essential blepharospasm.

In this study, we investigated gray matter density in essential blepharospasm (EB) patients, focusing on the duration of disease and severity of symptoms. We studied 32 patients (10 males and 22 females; age, 55.0 ± 6.5years) with EB and 48 controls (15 males and 33 females; age, 54.4 ± 10.3years) by using 3D T1-weighted magnetic resonance imaging and voxel-based morphometry. We defined an activity index (AI) that reflects the severity and duration of EB symptoms in each patient. The difference between the 2 groups was examined by statistical parametric mapping software (SPM8). After controlling for age, gray matter density increased in the bilateral primary sensorimotor cortex (S1M1) and cingulate gyrus. The gray matter density in the bilateral S1M1 was found to have a significant positive correlation with the duration of disease and a more robust correlation with AI. The correlation coefficients, after correcting for age, in the S1M1 and left cingulate gyrus were as follows: with duration, right S1M1, 0.72 (P<0.00001); left S1M1, 0.72 (P<0.00001); and left cingulate gyrus, 0.33 (not significant); and with AI, right S1M1, 0.81 (P<10(-7)); left S1M1, 0.74 (P<0.00001); and left cingulate gyrus, 0.43 (P<0.05). The increase in gray matter density in the S1M1 and cingulate gyrus might be a secondary effect caused by long-term hyperactivity in these areas instead of a predisposing factor.

Photophobia in essential blepharospasm--a positron emission tomographic study.

To localize regional alterations in cerebral glucose metabolism in essential blepharospasm (EB) patients with photophobia. We have studied 22 EB patients by performing positron emission tomography and [(18)F]-fluorodeoxyglucose analysis. The patients were classified into two subgroups, namely, EB with photophobia (P group) and EB without photophobia (NP group), and compared with a healthy control group (n = 44). There were no significant differences between the two patient groups with respect to the severity of motor symptoms or the duration for which the condition persisted. The FDG-PET images were analyzed using the statistical parametric mapping software. As compared to the control group, the P group exhibited significant hypermetabolism in the thalamus (P = 0.002), while the NP group exhibited significant hypometabolism in the dorsal midbrain, especially, in the superior colliculus (P = 0.005). The P group exhibited significant hypermetabolism in the thalamus and the dorsal midbrain as compared to the NP group (P < 0.001). These findings suggest that photophobia in EB patients may be associated with abnormal hyperactivity in the thalamus. Either hyperactivity of the thalamus or hypoactivity of the superior colliculus, or both may be associated with excessive blinking in these patients.

[Microbial contamination of nipradiol with and without benzalkonium chloride].

PURPOSE: To compare microbial contamination of nipradiol both with and without benzalkonium chloride (BAC). SUBJECTS AND METHODS: Twenty primary open angle glaucoma patients treated with nipradiol with BAC were studied. The nipradiol with BAC was switched to nipradiol without BAC. Four weeks after switching, the nipradiol without BAC was once again switched to nipradiol with BAC. The bottle caps, nozzles, filters, and solutions were cultured and examined for contamination. RESULTS: In nipradiol without BAC microorganisms were isolated from caps (30%), nozzles (50%), solutions (0%), and filters (15%), whereas in nipradiol with BAC they were isolated from caps (35%), nozzles (40%), and solutions (25%). The microorganisms in the nipradiol without BAC were coagulase-negative Staphylococci (38.2%) and Propionibacterium acnes (29.4%), and in the nipradiol with BAC they were coagulase-negative Staphylococci (20.5%), Alcaligenes xylosoxidans (12.8%). CONCLUSIONS: In nipradiol without BAC, the bacteria were detected outside the filters, but not in the solution. The rate of microbial contamination of the nipradiol without BAC was similar to that of the nipradiol with BAC. Both the bacteria detected from the nipradiol with and those detected in the solution without BAC consisted only of bacterial flora of the cul-de-sac and skin.

Prolonged constant eye misalignment leads to failure to develop binocular vision in childhood ocular myasthenia gravis.

PURPOSE: Variable eye misalignment and blepharoptosis in childhood ocular myasthenia gravis can lead to permanent binocular visual loss. However, a standard ophthalmologic intervention for this condition has yet to be fully established. This study investigated the influence of variable eye misalignment and asymmetric blepharoptosis on the development of binocular vision in childhood ocular myasthenia gravis. METHODS: The authors retrospectively reviewed clinical records of consecutive patients with childhood ocular myasthenia gravis whose age of onset was younger than 36 months and who had follow-up periods of more than 1 year. Five patients were enrolled and were treated medically with pyridostigmine or corticosteroids. Eye alignment, eye movements, and blepharoptosis were observed during the follow-up period. Stereoacuity was recorded before and at the end of follow-up using Titmus stereoscopic and major amblyoscopic tests. RESULTS: None of the patients had amblyopia or anisometropia, but all had blepharoptosis that improved within 2 weeks after medication was administered. There was only one case in which stereoacutiy failed to develop, and this patient had a long period of constant exotropia lasting 48 months. In the remaining four cases, there was constant exotropia lasting less than 4 months or intermittent exotropia throughout the follow-up period. All of these patients regained or maintained binocular vision. CONCLUSION: Prolonged constant eye misalignment may be attributable to impaired binocular vision, and prompt eye alignment may be necessary in childhood ocular myasthenia gravis. Therefore, treatment based on precise assessment by a neuro-ophthalmologist or pediatric ophthalmologist that evaluates even slight eye misalignment is essential in ensuring normal development of binocular vision.

Glucose hypometabolism in the visual cortex proportional to disease severity in patients with essential blepharospasm.

Essential blepharospasm (EB) causes difficulty in eyelid opening because of involuntary movements of the orbicularis oculi muscle. Patients with EB have functional visual loss due to sustained eyelid closure. We examined cerebral glucose metabolism in 39 patients with EB (12 men and 27 women; mean age, 52.1 years) by using positron emission tomography with 18F-fluorodeoxyglucose. Forty-eight eye open healthy subjects and 48 eye close healthy subjects served as controls. We analyzed and compared the data between the patients and controls by using both statistical parametric mapping (SPM) and regions of interest (ROIs). We defined ROIs on both sides of the posterior striate cortex, anterior striate cortex, extrastriate cortex, and thalamus. In SPM analysis, glucose hypometabolism were observed in both sides of the extrastriate cortex compared to eye open controls but not to eye close controls. We also observed a significant negative correlation between the Jankovic Rating Scale (JRS) sum score and relative glucose metabolism level in the striate cortex of these patients. ROI analysis, a significant correlation was observed between the JRS sum score and glucose metabolism level in the posterior (right: r = -0.53, P = .0005; left: r = -0.65, P = .00001) and anterior (right: r = -0.33, P = .04; left: r = -0.37, P = .02) striate cortices of patients with EB. We surmise that the interruption of visual input cause glucose hypometabolism in the visual cortex of patients with EB.

Optic disc and peripapillary morphology in unilateral nonarteritic anterior ischemic optic neuropathy and age- and refraction-matched normals.

PURPOSE: To compare optic disc morphologic features and peripapillary retinal nerve fiber layer (RNFL) thickness between the unaffected eyes of patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) and their affected eyes and the eyes of age- and refraction-matched normal control subjects. DESIGN: Cross-sectional comparative study. PARTICIPANTS: Thirty-one patients with unilateral NAION and 62 age- and refraction-matched normal control subjects. METHODS: Optic disc morphologic features and peripapillary RNFL thickness were evaluated in both eyes of patients with unilateral NAION and in one randomly chosen eye of the normal control subjects. MAIN OUTCOME MEASURES: Optic disc and cup parameters were measured using the Heidelberg Retina Tomograph II (Heidelberg Engineering GmbH, Dossenheim, Germany), and RNFL thickness was measured by scanning laser polarimetry with variable corneal compensation (GDx VCC; Carl Zeiss Meditec, Dublin, CA). RESULTS: There was no significant difference in the disc area between the NAION affected eyes and the unaffected fellow eyes. The cup area, cup-to-disc area ratio, cup volume, and cup shape measure were greater, whereas the peripapillary RNFL thickness was smaller in the former than the latter (P = 0.001 to approximately 0.043). When the unaffected eyes of patients with NAION and the age- and refraction-matched normal control eyes were compared, the disc area, cup area, cup-to-disc area ratio, cup volume, mean cup depth, and cup shape measure were smaller in the former (P = 0.0006 to approximately 0.03); there was no significant difference in the RNFL thickness between the two (P>0.06). CONCLUSIONS: A comparison of the eyes with NAION and the fellow eyes indicated that the cup was slightly larger in the former than in the latter, suggesting the acquired enlargement of the cupping after NAION develops. A comparison of the unaffected fellow eyes in patients with NAION and the age- and refraction-matched normal control eyes suggested that a smaller disc area and smaller cupping were predisposing risk factors for the development of NAION.

Glucose hypermetabolism in the thalamus of patients with essential blepharospasm.

Essential blepharospasm (EB) is classified as a form of focal dystonia characterized by involuntary spasms of the musculature of the upper face. The basic neurological process causing EB is not known. The purpose of this study was to investigate cerebral glucose metabolism in patients with EB whose symptoms were suppressed by an injection of botulinum-A toxin. Earlier studies were confounded by sensory feedback activities derived from dystonic symptom itself. Cerebral glucose metabolism was examined by positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) in 25 patients (8 men and 17 women; age 52.6 +/- 10.1 years) with EB. The patients were awake but with the spasms suppressed by an injection of botulinum-A toxin. Thirty-eight normal volunteers (14 men and 24 women; age 58.2 +/- 7.3 years) were examined as controls. The difference between the two groups was examined by statistical parametric mapping (SPM99). A significant increase in the glucose metabolism was detected in the thalamus and pons in the EB patients. Hyperactivity in the thalamus may be a key pathophysiological change common to EB and other types of focal dystonia. The activity of the striatum and cerebellum are likely to be sensory dependent.