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.

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.

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.

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.

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.

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.

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.

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.

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.

[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.

A case of anterior ischemic optic neuropathy associated with uveitis.

INTRODUCTION: Here, we describe a patient who presented with anterior ischemic optic neuropathy (AION) and subsequently developed uveitis. CASE: A 69-year-old man was referred to our hospital and initially presented with best-corrected visual acuities (BCVA) of 20/40 (right eye) and 20/1000 (left eye) and relative afferent pupillary defect. Slit-lamp examination revealed no signs of ocular inflammation in either eye. Fundus examination revealed left-eye swelling and a pale superior optic disc, and Goldmann perimetry revealed left-eye inferior hemianopia. The patient was diagnosed with nonarteritic AION in the left eye. One week later, the patient returned to the hospital because of vision loss. The BCVA of the left eye was so poor that the patient could only count fingers. Slit-lamp examination revealed 1+ cells in the anterior chamber and the anterior vitreous in both eyes. Funduscopic examination revealed vasculitis and exudates in both eyes. The patient was diagnosed with bilateral panuveitis, and treatment with topical betamethasone was started. No other physical findings resulting from other autoimmune or infectious diseases were found. No additional treatments were administered, and optic disc edema in the left eye improved, and the retinal exudates disappeared in 3 months. The patient's BCVA improved after cataract surgery was performed. CONCLUSION: Panuveitis most likely manifests after the development of AION.

Deepening of the upper eyelid sulcus caused by 5 types of prostaglandin analogs.

PURPOSE: Upper eyelid sulcus deepening has recently been reported as an adverse effect of prostaglandin (PG) eye drop use. However, no data are available regarding the frequency of upper eyelid sulcus deepening caused by different types of PG eye drops. We used 5 types of PG eye drops in Japanese subjects and examined the frequency of appearance of upper eyelid sulcus deepening in these subjects. PATIENTS AND METHODS: The study included 250 patients (250 eyes) diagnosed with primary open-angle glaucoma or ocular hypertension. Five healthy patients were included as controls. One eye of each patient was treated with one of the following PG eye drops for >3 months: latanoprost, travoprost, tafluprost, bimatoprost, and isopropyl unoprostone. A single-lens reflex camera was used to photograph the open eyelids. Three ophthalmologists independently judged the appearance of the deepened upper eyelid sulcus in the photographs of the 250 patients and 5 controls by comparing the right and left eyes. A subjective self-reported symptom questionnaire was also administered. RESULTS: Upper eyelid sulcus deepening was objectively (photograph) and subjectively (questionnaire) noted in 24.0% and 12.0%, 50.0% and 24.0%, 18.0% and 10.0%, 60.0% and 40.0%, and 8.0% and 10.0% of the patients in the latanoprost, travoprost, tafluprost, bimatoprost, and unoprostone groups, respectively. It occurred more frequently (objectively and subjectively) in the bimatoprost group than in the latanoprost, the tafluprost, and the unoprostone groups (P<0.001). CONCLUSION: Upper eyelid sulcus deepening frequently occurred with bimatoprost usage, and this effect should be sufficiently elucidated before starting bimatoprost treatment.

New-onset type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic neuritis associated with type 1 interferon therapy for chronic hepatitis C.

A 60-year-old woman developed type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic neuritis during type 1 interferon therapies for chronic hepatitis C. The diabetes mellitus was elicited by interferon-α plus ribavirin therapy, while the optic neuritis was induced after interferon-ß treatment, followed by interferon-α and ribavirin therapy. It is possible that type 1 interferons lead to the onset of the two autoimmune diseases by inducing disease-specific autoantibodies. Autoimmune disease is an infrequent complication of type 1 interferon treatment; however, once it has occurred, it may result in severe impairments. Patients undergoing type 1 interferon therapy should therefore be carefully monitored for any manifestations of autoimmune diseases.

Three-month evaluation of dorzolamide hydrochloride/timolol maleate fixed-combination eye drops versus the separate use of both drugs.

PURPOSE: To investigate the ocular hypotensive effect and safety of dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops. METHODS: The study cohort comprised 34 patients with either primary open-angle glaucoma or ocular hypertension who were being concomitantly treated with dorzolamide hydrochloride 1 % eye drops and timolol maleate 0.5 % eye drops. The dorzolamide hydrochloride 1 % and timolol maleate 0.5 % eye drops were replaced with dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops without any washout period. The intraocular pressure (IOP) was evaluated both before and 1 and 3 months after the treatment change. The patients were asked to complete a questionnaire on adherence to the treatment protocol 1 month after the change in treatment. RESULTS: The IOP was 15.5 ± 2.7 mmHg at the time of treatment change, 15.2 ± 2.7 mmHg at 1 month post-change, and 15.5 ± 2.9 mmHg at 3 months post-change, which is consistent with that before the treatment change (p = 0.286). Based on the completed questionnaire, following the treatment change, 50 % of patients felt a stinging sensation following administration of the eye drops and 11.8 % experienced blurred vision. In no case were the eye drops discontinued due to adverse reactions or insufficient IOP decrease. CONCLUSION: The replacement of concomitant treatment with dorzolamide hydrochloride 1 % and timolol maleate 0.5 % eye drops with dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops improved protocol adherence and preserved the IOP.

Effects of BAK-free travoprost treatment for 3 years in patients with normal tension glaucoma.

BACKGROUND: The purpose of this study was to evaluate the effects of benzalkonium (BAK)-free travoprost monotherapy administered for 3 years on intraocular pressure and visual field performance. METHODS: The intraocular pressure of 76 patients with normal tension glaucoma was monitored every 1-3 months. A Humphrey visual field test was performed every 6 months after treatment and compared with the results before treatment. Visual field performance was also evaluated by trend and event analysis. RESULTS: Thirty cases discontinued within 3 years. Mean intraocular pressure after 3 years of travoprost treatment (14.1 ± 2.4 mmHg) was significantly lower than that before treatment (16.8 ± 2.6 mmHg, P < 0.0001). There was no change in the mean deviation and pattern standard deviation as measured by Humphrey visual field test after 3 years of treatment compared with before treatment. Visual field performance was worse in one patient (2.8%) by trend analysis and five patients (13.9%) by event analysis. Treatment was discontinued in six cases (7.9%) due to the appearance of adverse reactions. CONCLUSION: BAK-free travoprost monotherapy was effective in reducing intraocular pressure for at least 3 years; however, visual field performance worsened in 2.8%-13.9% of patients with normal tension glaucoma.

Efficacy and safety of a switch to latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops from latanoprost 0.005% monotherapy.

BACKGROUND: The purpose of this prospective study was to investigate the intraocular pressure (IOP)-lowering effect and safety of latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops, now available in Japan. MATERIALS AND METHODS: Thirty-one patients diagnosed with primary open-angle glaucoma who had an insufficient intraocular pressure (IOP) decrease with latanoprost 0.005% eyedrop monotherapy were enrolled. The latanoprost 0.005% eyedrops were discontinued, and administration of latanoprost 0.005%/timolol maleate 0.5% fixed combination eyedrops was initiated without any washout period. IOP was compared before and at months 1, 3, and 6 after the switch. The incidence of adverse reactions was investigated at every follow-up visit. RESULTS: Mean IOP was 17.3 ± 2.7 mmHg before the switch, 15.5 ± 2.6 mmHg one month after the switch, 14.9 ± 2.4 mmHg 3 months after the switch, and 15.1 ± 2.2 mmHg 6 months after the switch, indicating that IOP decreased significantly after the change. The IOP reduction rate was 9.9% ± 11.5% after one month, 13.1% ± 10.9% after 3 months, and 11.2% ± 11.8% after 6 months. Two patients (6.5%) discontinued therapy due to adverse reactions (one case each of itchiness and bradycardia). CONCLUSION: When latanoprost 0.005% eyedrop monotherapy was replaced by latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops, IOP decreased significantly without increasing the frequency of administration, and safety was satisfactory.

Assessment of ocular hypotensive effect and safety 12 months after changing from an unfixed combination to a latanoprost 0.005% + timolol maleate 0.5% fixed combination.

BACKGROUND: Latanoprost 0.005% + timolol maleate 0.5% combined eyedrops were recently made available in Japan. We prospectively investigated the intraocular pressure (IOP)-lowering effect, visual preservation effect, and adverse reactions of a one-year administration of this fixed combination. METHODS: The subjects included 162 eyes from 162 patients diagnosed with either primary open-angle glaucoma or ocular hypertension and using an unfixed combination of latanoprost 0.005% and timolol maleate 0.5%. The unfixed combination was discontinued and replaced with the latanoprost 0.005% + timolol maleate 0.5% fixed combination with no washout period. IOP was measured before (baseline) and 3, 6, 9, and 12 months after the change. The mean deviation value of Humphrey field analysis was compared. Adverse reactions were examined at every follow-up. RESULTS: No significant differences were found between mean IOP values obtained at baseline (mean ± standard deviation, 15.2 ± 3.3 mmHg) 3 months (15.1 ± 3.2 mmHg), 6 months (15.3 ± 3.1 mmHg), 9 months (15.3 ± 3.1 mmHg), and 12 months (15.1 ± 3.2 mmHg) after the change from the unfixed to the fixed combination of eyedrops (P = 0.212). In addition, no significant differences were observed between mean deviation values obtained at baseline (-9.11 ± 6.94 dB) and 12 months (-10.08 ± 7.24 dB) after the change (P = 0.114). Thirty-one patients discontinued the fixed combination within 12 months of replacement, due to an insufficient IOP decrease (20 patients, 12.3%) and adverse reactions (11 patients, 6.8%). CONCLUSION: Following replacement of two eyedrop medications (latanoprost 0.005% and timolol maleate 0.5%) by one fixed combination (latanoprost 0.005% + timolol maleate 0.5%), IOP and visual field were preserved. However, 20% of the patients discontinued the new treatment because of an insufficient IOP decrease and complaints of adverse reactions.