Follow-up of retinal thickness and optic MRI after optic neuritis in anti-MOG antibody-associated disease and anti-AQP4 antibody-positive NMOSD.

BACKGROUND: Retinal atrophy in the chronic phase of optic neuritis (ON) in anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. METHODS: Patients with these diseases were repeatedly evaluated using optical coherence tomography (OCT) for the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) in the ON-involved eyes during relapse-free period after the first ON episode before relapse. Optic MRI with short tau inversion recovery (STIR) sequences was further evaluated retrospectively. RESULTS: Twelve patients with MOGAD (20 eyes with ON-involvement) and 14 with AQP4-Ab-positive NMOSD (16 eyes with ON-involvement) were enrolled. The progression of retinal atrophy ≥12 months after onset was observed in AQP4-Ab-positive NMOSD, but was not apparent in MOGAD. A decrease in retinal thickness by the same amount results in more severe visual impairment in AQP4-Ab-positive NMOSD. On optic MRI, the residual STIR hyperintensity in the optic nerves remained in the chronic phase in almost all eyes with ON in both diseases. Optic nerve atrophy occurred in all evaluated ON-involved eyes in AQP4-Ab-positive NMOSD, while it was observed in half of ON-involved eyes in MOGAD. CONCLUSIONS: Progression of retinal atrophy in the chronic phase has been observed in patients with AQP4-Ab-positive NMOSD, while it remains uncertain in patients with MOGAD. The visual impairments upon similar levels of retinal atrophy would be worse in AQP4-Ab-positive NMOSD, possibly attributable in part to a higher incidence of optic nerve atrophy in this disease.

Five-year visual outcomes after optic neuritis in anti-MOG antibody-associated disease.

INTRODUCTION: Optic neuritis (ON) is a major phenotype of clinical attack related to demyelinating neurological diseases of the central nervous system, including multiple sclerosis (MS), anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). As the concept of MOGAD is relatively new, the long-term visual outcomes after ON in MOGAD remains unclear. METHODS: To elucidate the long-term visual prognosis after ON in MOGAD, patients with MOGAD whose visual acuity were regularly followed for more than 5 years from the onset of ON were enrolled. Best-corrected visual acuity (BCVA) at nadir in the acute phase and at 1 and 5 years from onset was evaluated. The data from patients with MOGAD were compared with those from patients with MS or anti-AQP4-positive NMOSD. RESULTS: Twenty-three patients (31 ON-involved eyes) with MOGAD, 20 patients (24 ON-involved eyes) with MS, and 22 patients (24 ON-involved eyes) with anti-AQP4-positive NMOSD were evaluated. All BCVA at nadir, 1 year, and 5 years from the onset of ON were much worse in anti-AQP4-positive NMOSD than in MS (p = 0.0024) and MOGAD (p = 0.0014) patients. In MOGAD and anti-AQP4-positive NMOSD, the serum disease-specific antibody titer was not associated with the subsequent visual prognosis. Visual acuity had almost fully recovered spontaneously or shortly after initiating acute treatment in 22 of the 23 patients with MOGAD-ON. The administration of high-dose intravenous steroid therapy further facilitated early recovery of visual acuity. Meanwhile, a small fraction of patients with extensive optic nerve lesions involving the chiasma irreversibly experienced severe visual impairment despite appropriate acute treatment. CONCLUSION: Although a small fraction of patients with MOGAD who presented with extensive optic nerve lesions experienced irreversible severe visual impairment, the long-term visual outcomes after 5 years from ON in patients with MOGAD were generally as good as that in patients with MS and much better than that in patients with anti-AQP4-positive NMOSD.

Optic neuritis after ocular trauma in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.

OBJECTIVE: The aim of this study was to report the possible association between minor trauma to the eyes and the subsequent occurrence of optic neuritis in patients with serum anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: Herein, we present three patients who developed acute optic neuritis with visual disturbances after accidental minor trauma to their eyes, without any fundus abnormality or orbital floor fractures present. RESULTS: Two of the three patients had a preceding history of neurological disturbances compatible with NMOSD (e.g., myelitis, area postrema syndrome) before the occurrence of trauma. One patient was rapidly treated with steroid pulse therapy and plasmapheresis, and he fully recovered visual acuity. The other two, who were left untreated in the acute phase, had sequelae of severe visual disturbances in the affected eyes. CONCLUSIONS: These cases suggest possible association between minor trauma to the eyes and the subsequent occurrence of optic neuritis in patients with serum anti-AQP4 antibodies. Avoiding ocular trauma and early administration of steroid pulse therapy in response to optic neuritis after trauma are desired in such cases.

Rapid Administration of High-Dose Intravenous Methylprednisolone Improves Visual Outcomes After Optic Neuritis in Patients With AQP4-IgG-Positive NMOSD.

Objective: The purpose of this study was to elucidate the rapid impact of high-dose intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) on the eventual visual prognosis in patients with serum anti-aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) who had an attack of optic neuritis (ON). Methods: Data from 32 consecutive NMOSD patients (1 male and 31 female) with at least one ON attack, involving a total of 36 ON-involved eyes, were evaluated. The following variables at ON onset were evaluated: sex, age at the first ON episode, visual acuity at nadir, visual acuity after 1 year, duration from ON onset to treatment for an acute ON attack, cycles of high-dose intravenous methylprednisolone pulse therapy for the ON attack, and cycles of plasmapheresis for the ON attack. Among the 36 ON-involved eyes, 27 eyes were studied using orbital MRI with a short-T1 inversion recovery sequence and gadolinium-enhanced fat-suppressed T1 imaging before starting treatment in the acute phase. Results: In univariate analyses, a shorter duration from ON onset to the initiation of high-dose intravenous methylprednisolone pulse therapy favorably affected the eventual visual prognosis 1 year later (Spearman's rho = 0.50, p = 0.0018). The lesion length on orbital MRI was also correlated with the eventual visual prognosis (rho = 0.68, p < 0.0001). Meanwhile, the days to steroid pulse therapy and lesion length on orbital MRI did not show a significant correlation. These findings suggest that the rapidness of steroid pulse therapy administration affects the eventual visual prognosis independent of the severity of ON. In multivariate analysis, a shorter time from ON onset to the start of acute treatment (p = 0.0004) and a younger age at onset (p = 0.0071) were significantly associated with better visual outcomes. Conclusions: Rapid initiation of high-dose intravenous methylprednisolone pulse therapy is essential to preserve the eventual visual acuity in patients with serum AQP4-IgG-positive NMOSD. Once clinicians suspect acute ON with serum AQP4-IgG, swift administration of steroid pulse therapy before confirming the positivity of serum AQP4-IgG would be beneficial for preserving visual function.

Differences in Clinical Features of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis in White and Asian Race.

PURPOSE: To determine whether clinical features and visual outcomes of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) differ between White and Asian subjects. DESIGN: Multicenter retrospective cohort. METHODS: This was a multicenter study of 153 subjects who were White or Asian with a history of adult-onset (age 18 years or older) optic neuritis (ON) and positive MOG-IgG serology by cell-based assay. Subjects were enrolled from 2 unpublished cohorts (January 2017-November 2019) and 9 published cohorts with case-level data available (2012-2018). Subjects with alternative etiologies of demyelinating disease and positive or lack of aquaporin-4-IgG serology result were excluded. The main outcome measurements were clinical features and final visual outcomes. RESULTS: Of the 153 subjects who were White (n = 80) or Asian (n = 73) included in the study, 93 (61%) were women, mean age of onset was 40.8 ± 14.9 years, and median follow-up was 35.2 months (range: 1-432 months); all of these characteristics were similar between White and Asian subjects. White subjects were more likely to have recurrent ON (57 [71%] vs 20 [27%]; P = .001) and extra-optic nerve manifestations (35 [44%] vs 8 [11%]; P = .001). Optic disc swelling, neuroimaging findings, presenting visual acuity (VA), treatment, and final VA did not differ according to subjects' race. Despite the high prevalence of severe visual loss (<20/200) during nadir, most subjects had good recovery of VA (>20/40) at final examination (51/77 [66%] White subjects vs 52/70 [74%] Asian subjects). CONCLUSION: White subjects with MOG-ON were more likely to have recurrent disease and extra-optic nerve manifestations. Visual outcomes were similar between White and Asian subjects.

Chloride imbalance is involved in the pathogenesis of optic neuritis in neuromyelitis optica.

Chloride imbalance between the serum and the cerebrospinal fluid (CSF) has been recently shown to exist in the acute phase of neuromyelitis optica (NMO). In this report, we studied the relation between the quotient of chloride (QCl) and the severity of optic neuritis (ON) in NMO patients. There was a positive correlation (R = 0.67; p < 0.05) between QCl and the length of ON-lesion. The visual prognosis also showed a positive correlation with QCl in the acute phase (R = 0.58; p < 0.05). These results support the theory that chloride imbalance between serum and CSF may trigger the ON in NMO spectrum disorders.

Subclinical retinal atrophy in the unaffected fellow eyes of multiple sclerosis and neuromyelitis optica.

We compared the retinal thickness in the unaffected eyes among the following subtypes of unilateral optic neuritis (ON): multiple sclerosis (MS-ON), neuromyelitis optica spectrum disorder with anti-AQP4 autoantibody (AQP4-ON), patients with serum anti-MOG antibody (MOG-ON), and idiopathic ON. In the chronic phase, macular GCC and circum-papillary RNFL in the unaffected eyes were both atrophied in MS-ON and AQP4-ON, but were not atrophied in the others. Titers of anti-AQP4-Ab was suggested to be associated with such latent neurodegenerative process in AQP4-ON. Long-term follow up of OCT is recommended even in the unaffected side in MS-ON and AQP4-ON.

Different etiologies and prognoses of optic neuritis in demyelinating diseases.

We compared the clinical features of optic neuritis (ON) that are frequently observed in various central nervous system demyelinating diseases, including multiple sclerosis (MS), anti-aquaporin 4 (AQP4) antibody- and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody-related diseases. Almost all the AQP4-ON patients were female, whereas half of the MOG-ON patients were male. The ON-onset age was younger in MS-ON and was older in AQP4-ON. The ON-lesion detected using optic MRI in the acute phase was longer in MOG-ON and showed severe swelling and twisting. The worst visual acuity was similar between the diseases; however, the final visual acuity was significantly worse in AQP4-ON.

Tardily accelerated neurologic deterioration in two-step thallium intoxication.

Thallium intoxication was reported in cases with accidental ingestion, suicide attempt, and criminal adulteration. Reported cases were mostly one-time ingestion, therefore, the clinical course of divisional ingestion has not been fully known. Here, we report a case with two-step thallium intoxication manifesting as tardily accelerated neurologic deterioration. A 16-year-old adolescent was cryptically poisoned with thallium sulfate twice at an interval of 52days. After the first ingestion, neurologic symptoms including visual loss, myalgia, and weakness in legs developed about 40days after the development of acute gastrointestinal symptoms and alopecia. After the second ingestion, neurologic symptoms deteriorated rapidly and severely without gastrointestinal or cutaneous symptoms. Brain magnetic resonance imaging exhibited bilateral optic nerve atrophy. Nerve conduction studies revealed severe peripheral neuropathies in legs. Thallium intoxication was confirmed by an increase in urine thallium egestion. Most of the neurologic manifestations ameliorated in two years, but the visual loss persisted. The source of thallium ingestion was unraveled afterward because a murder suspect in another homicidal assault confessed the forepast adulteration. This discriminating clinical course may be attributable to the cumulative neurotoxicity due to the longer washout-time of thallium in the nervous system than other organs. It is noteworthy that the divisional thallium intoxication may manifest as progressive optic and peripheral neuropathy without gastrointestinal or cutaneous symptoms.

Lesion length of optic neuritis impacts visual prognosis in neuromyelitis optica.

OBJECTIVES: The visual acuity prognoses of patients with neuromyelitis optica (NMO) are worse than those with optic neuritis (ON) caused by other diseases. Predicting the prognoses of ON at the time of onset is important for selecting treatments for NMO patients. METHODS: Twenty-three consecutive anti-aquaporin-4 autoantibody-positive NMO patients who presented with ON and had contrast-enhanced optic MRIs in the acute phase of their first ON episode were examined. Optical coherence tomographies (OCTs) were also examined for 22 of them. The visual acuity at the final follow-up, as assessed with the logMAR scale more than three years after ON onset, served as the outcome measure. These variables were also collected from 12 patients with serum anti-myelin oligodendrocyte glycoprotein antibody (anti-MOG-Ab). RESULTS: The strongest predictor of visual prognosis was the axial ON lesion length in the acute phase (R=0.747, p<0.0001), which was not observed in patients with anti-MOG-Ab. Specifically, the ON lesion length within the intra-orbit and canalicular segments exhibited the strongest correlation with visual prognosis (R=0.783, p<0.0001). The ON onset age was also correlated with visual prognosis (R=0.435, p=0.0338). OCT data in the chronic phase also showed a correlation with visual prognosis, but they were much weaker than the ON lesion length in the acute phase. CONCLUSIONS: The ON lesion length in the acute phase was an important predictor of the visual prognoses of NMO patients.

The reduction of temporal optic nerve head microcirculation in autosomal dominant optic atrophy.

PURPOSE: To evaluate the optic nerve head (ONH) microcirculation in autosomal dominant optic atrophy (ADOA) patients. METHODS: This study comprised 22 eyes of 12 ADOA patients, diagnosed according to clinical findings including family history and the presence of mutations in the OPA1 gene. Twenty-four normal eyes of 24 age-matched subjects, with either the right or left eye randomly selected for use, served as controls. Circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and mean blur rate (MBR) in the ONH were determined with optical coherence tomography (OCT) and laser speckle flowgraphy (LSFG), respectively. For each ONH quadrant (superior, temporal, inferior and nasal), the MBR and cpRNFLT ratio was also calculated by dividing tissue MBR in that quadrant by tissue MBR in the entire ONH and by dividing cpRNFLT in that quadrant by cpRNFLT in the entire ONH respectively. RESULTS: Mean blur rate (MBR) in all quadrants was significantly lower in the ADOA patients than in the controls (p < 0.001 in each). The MBR ratio was significantly lower in the ADOA patients only in the temporal quadrant (p < 0.001). Similarly, cpRNFLT was lower in the ADOA patients in all quadrants (p < 0.001 in each), and the cpRNFLT ratio was lower in the temporal quadrant (p < 0.001). CONCLUSION: Reduced blood flow in the temporal optic disc in ADOA patients is associated with reduced temporal cpRNFLT, suggesting that both are caused by damage to the papillomacular bundle. The anatomical characteristics of the papillomacular bundle may make it especially susceptible to mitochondrial dysfunction-induced damage, which occurs in ADOA.

Biomineralization of hydroxyapatite on DNA molecules in SBF: morphological features and computer simulation.

The hydroxyapatite (HA) formation on the DNA molecules in SBF was examined. After immersion for four weeks in SBF at 36.5 °C, the HA crystallites of ~1-14 µm in diameter grew on the surface of DNA molecules. Various morphologies were successfully observed through scanning electron microscopy analysis. The Ca/P mol ratio (1.1-1.5) in HA was estimated by energy dispersive X-ray analysis. Original peaks of both of DNA and HA were characterized by Fourier transform infrared spectroscopy. The molecular orbital computer simulation has been used to probe the interaction of DNA with two charge-balancing ions, i.e., CaOH(+) and CaH2PO4(+). The adsorption enthalpy of the two ions on ds-DNA and/or ss-DNA having large negative value (~ -60 kcal/mol per charge-balancing ion) was the evidence for the interface in mineralization of HA in SBF.

The influence of posture change on ocular blood flow in normal subjects, measured by laser speckle flowgraphy.

PURPOSE: To investigate, using laser speckle flowgraphy (LSFG), the autoregulation of ocular blood flow (BF) in response to posture change. METHODS: This study comprised 20 healthy volunteers (mean age 30.0 ± 8.5). The mean blur rate (MBR) of the ocular circulation in the subjects was assessed in both a sitting and a supine position every 2 min over the course of 10 min. Baseline measurements of the MBR at the optic nerve head (ONH) and the choroid were taken in a sitting position. Increases in the MBR ratio in a supine position were calculated with reference to this baseline. Intraocular pressure (IOP), systemic blood pressure and heart rate in the brachial artery were also recorded. RESULTS: In the ONH, the MBR ratio increased significantly over the baseline after 2 min (104.8 ± 5.0%, p = 0.001) and 4 min (104.4 ± 5.6%, p = 0.005), in a supine position, but decreased to the initial level after only 6 min. In the choroid, on the other hand, while the MBR ratio also increased significantly after 2 min in a supine position (113.7 ± 8.1%, p < 0.001), it kept this significant increase over the time course of 10 min. After 10 min in a supine position, IOP increased significantly (p < 0.001), systolic blood pressure decreased significantly (p < 0.001), but diastolic blood pressure did not change significantly compared to the baseline. (p = 0.07) CONCLUSIONS: ONH and choroidal circulation have significantly different hemodynamics in response to posture change in healthy volunteers. This finding suggests that LSFG enables us to assess the autoregulation of BF in the ONH.

Global scenarios of air pollutant emissions from road transport through to 2050.

This paper presents global scenarios of sulphur dioxide (SO(2)), nitrogen oxides (NO(x)), and particulate matter (PM) emissions from road transport through to 2050, taking into account the potential impacts of: (1) the timing of air pollutant emission regulation implementation in developing countries; (2) global CO(2) mitigation policy implementation; and (3) vehicle cost assumptions, on study results. This is done by using a global energy system model treating the transport sector in detail. The major conclusions are the following. First, as long as non-developed countries adopt the same vehicle emission standards as in developed countries within a 30-year lag, global emissions of SO(2), NO(x), and PM from road vehicles decrease substantially over time. Second, light-duty vehicles and heavy-duty trucks make a large and increasing contribution to future global emissions of SO(2), NO(x), and PM from road vehicles. Third, the timing of air pollutant emission regulation implementation in developing countries has a large impact on future global emissions of SO(2), NO(x), and PM from road vehicles, whereas there is a possibility that global CO(2) mitigation policy implementation has a comparatively small impact on them.