Early-Onset Ocular Motor Cranial Neuropathy Is a Strong Predictor of Dementia: A Nationwide, Population-Based Cohort Study.

PURPOSE: To assess the risk of dementia in individuals with newly diagnosed ocular motor cranial neuropathy (OMCN). DESIGN: A nationwide, population-based cohort study using authenticated data from the Korean National Health Insurance Service (KNHIS). PARTICIPANTS: This study included 60 781 patients with OMCN who received a diagnosis between 2010 and 2017 and were followed up through 2018, with an average follow-up of 3.37 ± 2.21 years with a 1-year lag. After excluding patients with disease related to oculomotor dysfunction preceding the OMCN diagnosis, a total of 52 076 patients with OMCN were established. Of these, 23 642 patients who had participated in the National Health Screening Program (NHSP) within 2 years before the OMCN diagnosis were included. After applying the exclusion criteria, the final cohort comprised 19 243 patients and 96 215 age and sex-matched control participants without OMCN. METHODS: We identified patients with newly diagnosed OMCN in the KNHIS database and collected participant characteristics from the health checkup records of the NHSP. The study end point was determined by the first claim with a dementia diagnostic code and antidementia medications. The association of OMCN with dementia risk was examined using Cox proportional hazards regression analysis, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: The main outcome measures were hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) development in patients with OMCN relative to those without OMCN. RESULTS: Patients with newly diagnosed OMCN demonstrated higher metabolic comorbidities than those without OMCN. New OMCN was associated with an elevated risk of ACD (HR, 1.203; 95% CI, 1.113-1.300), AD (HR, 1.137; 95% CI, 1.041-1.243), and VaD (HR, 1.583; 95% CI, 1.286-1.948), independent of potential confounding factors. The younger age groups exhibited a stronger association between OMCN and ACD (HR, 8.690 [< 50 years] vs. 1.192 [≥ 50 years]; P = 0.0004; HR, 2.517 [< 65 years] vs. 1.099 [≥ 65 years]; P < 0.0001). CONCLUSIONS: This nationwide population-based study assessed the association between OMCN and dementia risk. Our results demonstrated a robust relationship between OMCN and the risk of dementia, particularly in the younger population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes.

BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis. RESULTS: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION. CONCLUSION: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON.

Risk of central nervous system demyelinating attack or optic neuritis recurrence after pediatric optic neuritis in Korea.

PURPOSE: To investigate the rate of development of symptomatic central nervous system (CNS) demyelinating attacks or recurrent optic neuritis (ON) after the first episode of ON and its risk factors for Korean pediatric patients. METHODS: This multicenter retrospective cohort study included the patients under 18 years of age (n=132) diagnosed with ON without previous or simultaneous CNS demyelinating diseases. We obtained the clinical data including the results of neuro-ophthalmological examinations, magnetic resonance images (MRIs), antibody assays, and laboratory tests. We investigated the chronological course of demyelinating disease with respect to the occurrence of neurological symptoms and/or signs, and calculated the 5-year cumulative probability of CNS demyelinating disease or ON recurrence.  RESULTS: During the follow-up period (63.1±46.7 months), 18 patients had experienced other CNS demyelinating attacks, and the 5-year cumulative probability was 14.0±3.6%. Involvement of the extraorbital optic nerve or optic chiasm and asymptomatic lesions on the brain or spinal MRI at initial presentation were significant predictors for CNS demyelinating attack after the first ON. The 5-year cumulative probability of CNS demyelinating attack was 44.4 ± 24.8% in the AQP4-IgG group, 26.2±11.4% in the MOG-IgG group, and 8.7±5.9% in the double-negative group (P=0.416). Thirty-two patients had experienced a recurrence of ON, and the 5-year cumulative probability was 24.6±4.0%. In the AQP4-IgG group, the 5-year cumulative probability was 83.3±15.2%, which was significantly higher than in the other groups (P<0.001). CONCLUSIONS: A careful and multidisciplinary approach including brain/spinal imaging and antibody assay can help predict further demyelinating attacks in pediatric ON patients.

Optical Coherence Tomography Parameters and Optimal Cut-off Values for Predicting Visual Prognosis in Ethambutol-Induced Optic Neuropathy.

BACKGROUND: The objective of this study was to evaluate the prognostic value of optical coherence tomography (OCT) parameters in patients with ethambutol-induced optic neuropathy (EON) and establish their optimal cut-off values for predicting visual acuity outcomes. METHODS: A retrospective cross-sectional study was conducted on 64 eyes of 32 patients with EON who underwent OCT. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were measured using Cirrus high-definition OCT (HD-OCT) within 3 months after EON diagnosis. Visual acuity of patients was recorded and analyzed at the first visit, the 1-year visit, and the latest visit. Prognostic capacities of OCT parameters for visual prognosis were evaluated and their optimal cut-off values for predicting final visual acuity were established. RESULTS: Increased pRNFL thickness was significantly associated with better visual acuity at 1 year postdiagnosis and the latest visit. A significant association was established between increased pRNFL thickness and a higher rate of recovery to visual acuity >20/25 at 1 year postdiagnosis. Receiver-operating characteristic curves identified ideal cut-off values for OCT parameters as follows: pRNFL thickness of 83 µm (sensitivity 100%, specificity 48.3%) and mGCIPL thickness of 74 µm (sensitivity 100%, specificity 83.3%) for visual acuity >20/25 at 1 year, mGCIPL thickness of 61 µm (sensitivity 85.7%, specificity 71.4%) for visual acuity >20/40 at 1 year, with corresponding AUCs exceeding 0.7. CONCLUSIONS: Both pRNFL and mGCIPL thickness possess potential values for predicting visual outcomes in patients with EON. Future research should continue to explore the utility of OCT parameters in EON prognosis.

Cranial Nerve Palsy and Risk of Kidney Cancer: A Nationwide Population-Based Study.

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.

Hormone Replacement Therapy and the Incidence of Nonarteritic Anterior Ischemic Optic Neuropathy: a Nationwide Population-Based Study (2009-2018).

PURPOSE: This study aimed to assess the association between hormone replacement therapy (HRT) and the prevalence of nonarteritic anterior ischemic optic neuropathy (NAION) in menopausal women using national data from the entire Korean population. METHODS: The health screening data of 1,381,605 women between 40 and 90 years of age collected by the National Health Insurance Service (NHIS) of Korea between January 1, 2009, and December 31, 2018, were retrospectively reviewed. Before data analysis, the potential cofounders were adjusted for among all participants. Based on HRT use and its duration (classified into four groups), the hazard ratio (HR) and 95% confidence interval (CI) of NAION development were calculated via a Cox proportional hazards regression analysis using the nonuser group as a reference. RESULTS: Overall, 7824 NAION diagnoses were made during the mean follow-up of 8.22 years (standard deviation: 1.09 years) in 1,381,605 post-menopausal women. NAION was more common in the HRT group than in the non-HRT group (HR [95% CI]: 1.268 [1.197-1.344]). Furthermore, the risk of NAION increased along with increased HRT duration (p < 0.0001). In the multivariate analysis, the adjusted HRs of the < 2-year HRT group, the 2-5-year HRT group, and the ≥ 5-year HRT group were 1.19 (95% CI: 1.10-1.28), 1.3 (95% CI: 1.17-1.45), and 1.473 (95% CI: 1.31-1.65), respectively. Compared to women younger than 65 years, the HR of HRT for NAION was significantly higher than that of women older than 65 years (p < 0.0001). CONCLUSION: Our population-based cohort study found that HRT was significantly associated with increased incidence of NAION. The incidence of NAION also increased with the duration of HRT.

Early response to intravenous methylprednisolone therapy for restrictive myopathy in patients with thyroid eye disease.

PURPOSE: To report the therapeutic efficacy of intravenous methylprednisolone (IVMP) in patients with restrictive myopathy caused by thyroid eye disease (TED). METHODS: The present prospective uncontrolled study comprised 28 patients with TED and restrictive myopathy who presented with diplopia that had developed within 6 months before their visit. All patients were treated with IVMP for 12 weeks. Deviation angle, limitation of extraocular muscle (EOM) movement, binocular single vision score, Hess score, clinical activity score (CAS), modified NOSPECS score, exophthalmometric value, and the size of EOMs on computed tomography were evaluated. The patients were divided into two groups: those whose deviation angle had decreased or remained unchanged 6 months after treatment (group 1; n = 17) and those whose deviation angle had increased in that time (group 2; n = 11). RESULTS: The mean CAS of the whole cohort significantly decreased from baseline to 1 month and 3 months after treatment (P = 0.03 and P = 0.02, respectively). The mean deviation angle significantly increased from baseline to 1, 3, and 6 months (P = 0.01, P < 0.01, and P < 0.01, respectively). The deviation angle decreased in 10 (36%), remained constant in seven (25%), and increased in 11 (39%) of the 28 patients. When groups 1 and 2 were compared, no single variable was identified as a cause of deviation angle deterioration (P > 0.05). CONCLUSIONS: When treating patients with TED who have restrictive myopathy, physicians should be aware that some patients show worsening of the strabismus angle despite inflammation control with IVMP therapy. Uncontrolled fibrosis can result in motility deterioration.

Ocular motility disorders following coronavirus disease-19 vaccination.

PURPOSE: To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination. METHODS: Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed. RESULTS: Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22-81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0-28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively. CONCLUSION: This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis.

Dynamic Changes in Metabolic Status Are Associated With Risk of Ocular Motor Cranial Nerve Palsies.

BACKGROUND: To investigate whether recovery from or development of metabolic syndrome (MetS) in a population is associated with an altered risk for ocular motor cranial nerve palsy (CNP). METHODS: This cohort study included 4,233,273 adults without a history of ocular motor cranial nerve palsy (ocular motor CNP) who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2011. They were followed up until December 31, 2018. Participants were categorized into a MetS-free, MetS-developed, MetS-recovered, or MetS-chronic group. A multivariable Cox proportional hazard regression model was used. Model 3 was adjusted for age, sex, smoking status, alcohol consumption, and physical activity. RESULTS: Compared with the MetS-free group, the MetS-chronic group had the highest risk of ocular motor CNP (hazard ratio [HR]: 1.424; 95% confidential interval [CI]: 1.294-1.567, Model 3), followed by the MetS-developed group (HR: 1.198, 95% CI: 1.069-1.343), and the MetS-recovered group (HR: 1.168, 95% CI: 1.026-1.311) after adjusting for potential confounders. The hazard ratio of ocular motor CNP in men with chronic MetS was 1.566 (95% CI, 1.394-1.761) while that of women with chronic MetS was 1.191 (95% CI, 1.005-1.411). Among age groups, those in their 30s and 40s showed the highest association between dynamic MetS status and ocular motor CNP. CONCLUSIONS: In our study, recovering from MetS was associated with a reduced risk of ocular motor CNP compared with chronic MetS, suggesting that ocular motor CNP risk could be managed by changing MetS status.

Non-Arteritic Ischemic Optic Neuropathy Following COVID-19 Vaccination in Korea: A Case Series.

BACKGROUND: To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea. METHODS: This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION. RESULTS: The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43-77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1-41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit. CONCLUSION: Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION.

Factors affecting the health-promoting behavior of thyroid cancer survivors: comparison by stage of cancer survivorship.

PURPOSE: The purpose of this study was to identify differences in factors affecting health-promoting behaviors according to the survival stage of thyroid cancer survivors. METHODS: This descriptive cross-sectional study analyzed data from 354 thyroid cancer survivors after diagnosis. The survivors were divided into three stages: (1) the acute stage (< 2 years after diagnosis), (2) extended stage (2-5 years after diagnosis), and (3) permanent stage (≥ 5 years after diagnosis). To measure health-promoting behavior, the revised Korean version of the Health Promoting Lifestyle Profile questionnaires was used. The factors affecting the health-promoting behavior included social support, self-efficacy, fear of recurrence, and symptoms. Multiple regression analysis was used to analyze factors affecting the health-promoting behavior according to survival stage. RESULT: The factors affecting the health-promoting behavior of thyroid cancer survivors differed by survival stage. In the acute stage, the factors of health-promoting behavior were self-efficacy (t = 4.76, p < .001) and social support (t = 3.54, p < .001). In the extended stage, symptoms (t = - 3.65, p < .001), social support (t = 2.61, p = .011), fear of recurrence (t = 2.18, p = .032), and receipt of radioiodine treatment (t = - 2.18, p = .032) were found to be significant variables that affected health-promoting behaviors. In the permanent stage, social support (t = 2.79, p = .007), receipt of radioiodine treatment (t = - 3.21, p = .002), and age (t = - 2.77, p = .007) were significant variables that affected health-promoting behaviors. CONCLUSION: The experience of thyroid cancer survivors varies as they progress through the survival stages; thus, health-promotion interventions should be tailored to each survival stage.

Liver enzymes and risk of ocular motor cranial nerve palsy: a nationwide population-based study.

This study aimed to assess the associations between liver enzymes including γ-glutamyl transferase (GGT) and the development of ocular motor cranial nerve palsy (CNP) using the National Sample Cohort database from Korea's National Health Insurance Service. We analyzed data from 4,233,273 medical screening examinees aged 20 years or more in 2009. Study participants were followed up until December 31, 2018. A Cox proportional hazard regression analysis was performed for quartiles of liver enzymes to determine the linkage between each value and ocular motor CNP using quartile 1 as a reference after adjusting for potential confounders. A total of 5,807 (0.14%) patients developed ocular motor CNP during the follow-up period of 8.22 ± 0.94 years. The incidence of ocular motor CNP gradually increased as the GGT levels increased. The highest quartile of the GGT group had hazard ratio (HR) of 1.245 (95% confidence interval [CI], 1.136-1.365). Regarding alanine aminotransferase (ALT), the highest quartile of the ALT group had HR of 1.141 (95% CI, 1.049-1.241). However, the incidence of ocular motor CNP did not gradually increase as the ALT levels increased. The coexistence of the increased level of GGT, metabolic syndrome, and obesity showed a stronger association with ocular motor CNP development (HR, 1.331; 95% CI, 1.173, 1.511) compared to having a single factor or two factors. In conclusion, our population-based cohort study demonstrated a significant association between serum GGT level and the incidence of ocular motor CNP, suggesting that GGT could be a new clinical marker for predicting the occurrence of ocular motor CNP.

Association of mental disorders and strabismus among South Korean children and adolescents: a nationwide population-based study.

PURPOSE: The aim of this study is to determine the association between mental disorders and strabismus in South Korean children and adolescents. METHODS: Using data from the Korean National Health Claims Database from 2011 to 2017, the prevalence rates of mental illnesses and odds ratio were calculated. Children and adolescents (1-19 years) with strabismus and their randomly selected nonstrabismic age- and sex-matched controls (1:1) were enrolled. The odds ratios were adjusted for preterm birth, cerebral palsy, and mental retardation. Subgroup analysis was performed according to sex and the type of strabismus. RESULTS: A total of 327,076 subjects (male, 158,597; female, 168,479) identified as strabismus patients were enrolled. After adjusting for preterm birth, cerebral palsy, and mental retardation, the corrected odds ratio of overall mental illness was 1.10 (95% CI, 1.08-1.12) for the strabismus group compared to the controls: 1.7 (95% CI, 1.62-1.78) for developmental disorder, 1.36 (95% CI, 1.27-1.45) for pervasive developmental disorder (autism), 1.14 (95% CI, 1.10-1.17) for attention-deficit hyperactivity disorder (ADHD), 1.15 (95% CI, 1.05-1.27) for obsessive-compulsive disorder (OCD), 1.08 (95% CI, 1.05-1.11) for pediatric behavioral and emotional disorders, 0.93 (95% CI, 0.88-0.99) for post-traumatic stress disorder (PTSD), and 0.85 (95% CI, 0.82-0.89) for tic disorder. CONCLUSION: South Korean children and adolescents with strabismus had a higher relative risk for various types of mental disorders such as a developmental disorder, autism, ADHD, and OCD than the controls, whereas they had a relatively lower risk of tic disorder.

Leber's hereditary optic neuropathy following unilateral painful optic neuritis: a case report.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by acute or subacute, painless, bilateral visual loss. LHON is often misdiagnosed as optic neuritis at an early stage because of the similarity of their clinical presentation. To date, there has been no reported case of actual optic neuritis and LHON in one patient. CASE PRESENTATION: A 40-year-old, healthy man was referred to our clinic with acute painful visual loss in the right eye for 2 weeks. In the right eye, visual acuity decreased to 20/40, and the Ishihara colour test score was 8/14 with a relative afferent pupillary defect. Optic disc swelling was found only in the right eye, and magnetic resonance imaging revealed enhancement of the the right optic nerve, consistent with optic neuritis. After receiving 1 g of intravenous methylprednisolone daily for three days, his ocular pain resolved, and visual acuity improved to 20/20 within 2 weeks. Seven months later, the patient developed acute painless visual loss in the right eye. Visual acuity decreased to 20/200 in the right eye. There was no response to the intravenous methylprednisolone therapy at that time. Eight months later, he developed subacute painless visual loss in the left eye. Genetic testing for LHON was performed and revealed the pathologic mtDNA 11778 point mutation. CONCLUSIONS: We report a case with painful unilateral optic neuritis preceding the onset of LHON. Even if a typical optic neuritis patient has completely recovered from steroid treatment once in the past, it is advisable to keep in mind the possibility of LHON if acute or subacute loss of vision subsequently or simultaneously occurs in both eyes and does not respond to steroids.

Computer-aided recognition of myopic tilted optic disc using deep learning algorithms in fundus photography.

BACKGROUND: It is necessary to consider myopic optic disc tilt as it seriously impacts normal ocular parameters. However, ophthalmologic measurements are within inter-observer variability and time-consuming to get. This study aimed to develop and evaluate deep learning models that automatically recognize a myopic tilted optic disc in fundus photography. METHODS: This study used 937 fundus photographs of patients with normal or myopic tilted disc, collected from Samsung Medical Center between April 2016 and December 2018. We developed an automated computer-aided recognition system for optic disc tilt on color fundus photographs via a deep learning algorithm. We preprocessed all images with two image resizing techniques. GoogleNet Inception-v3 architecture was implemented. The performances of the models were compared with the human examiner's results. Activation map visualization was qualitatively analyzed using the generalized visualization technique based on gradient-weighted class activation mapping (Grad-CAM++). RESULTS: Nine hundred thirty-seven fundus images were collected and annotated from 509 subjects. In total, 397 images from eyes with tilted optic discs and 540 images from eyes with non-tilted optic discs were analyzed. We included both eye data of most included patients and analyzed them separately in this study. For comparison, we conducted training using two aspect ratios: the simple resized dataset and the original aspect ratio (AR) preserving dataset, and the impacts of the augmentations for both datasets were evaluated. The constructed deep learning models for myopic optic disc tilt achieved the best results when simple image-resizing and augmentation were used. The results were associated with an area under the receiver operating characteristic curve (AUC) of 0.978 ± 0.008, an accuracy of 0.960 ± 0.010, sensitivity of 0.937 ± 0.023, and specificity of 0.963 ± 0.015. The heatmaps revealed that the model could effectively identify the locations of the optic discs, the superior retinal vascular arcades, and the retinal maculae. CONCLUSIONS: We developed an automated deep learning-based system to detect optic disc tilt. The model demonstrated excellent agreement with the previous clinical criteria, and the results are promising for developing future programs to adjust and identify the effect of optic disc tilt on ophthalmic measurements.

Anamorsin attenuates cupric chloride-induced dopaminergic neuronal cell death.

Neurodegenerative diseases are associated with elevated levels of metal elements, which are well-known inducers of reactive oxygen species (ROS) in cells. Because dopaminergic neurons in the substantia nigra are vulnerable to ROS, dysregulation of metals and the resulting accumulation of ROS could be a cause of dopaminergic neurodegeneration. In this study, we showed that overexpression of anamorsin protected MN9D dopaminergic neuronal cells from cupric chloride-induced death. This cytoprotection was achieved by specifically decreasing ROS levels. As determined by mini two-dimensional electrophoretic assay, an acidic shift of anamorsin occurred during drug-induced death, which seemed to be mediated by oxidative modification of three of its CXXC motifs. Consequently, drug-induced dissociation of ASK1 from Trx1 and subsequent phosphorylation of JNK and p38 MAPK were inhibited in MN9D cells overexpressing anamorsin. Taken together, our results indicate that anamorsin exerts a neuroprotective effect by reducing intracellular ROS levels and subsequently attenuating activated stress-activated MAP kinases pathways.

Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet.

Hypothalamic inflammation has been known as a contributor to high-fat diet (HFD)-induced insulin resistance and obesity. Myeloid-specific sirtuin 1 (SIRT1) deletion aggravates insulin resistance and hypothalamic inflammation in HFD-fed mice. Neurogranin, a calmodulin-binding protein, is expressed in the hypothalamus. However, the effects of myeloid SIRT1 deletion on hypothalamic neurogranin has not been fully clarified. To investigate the effect of myeloid SIRT1 deletion on food intake and hypothalamic neurogranin expression, mice were fed a HFD for 20 weeks. Myeloid SIRT1 knockout (KO) mice exhibited higher food intake, weight gain, and lower expression of anorexigenic proopiomelanocortin in the arcuate nucleus than WT mice. In particular, KO mice had lower ventromedial hypothalamus (VMH)-specific neurogranin expression. However, SIRT1 deletion reduced HFD-induced hypothalamic neurogranin. Furthermore, hypothalamic phosphorylated AMPK and parvalbumin protein levels were also lower in HFD-fed KO mice than in HFD-fed WT mice. Thus, these findings suggest that myeloid SIRT1 deletion affects food intake through VMH-specific neurogranin-mediated AMPK signaling and hypothalamic inflammation in mice fed a HFD.

A case report of isolated orbital vasculitis mimicking retinal migraine: A potential cause of recurrent transient monocular blindness and ipsilateral headache.

BACKGROUND: Retinal migraine is an important differential diagnosis of recurrent transient monocular blindness accompanied by headache when other etiologies are excluded. Here, we report a case of orbital vasculitis which initially mimicked retinal migraine. CASE REPORT: A 47-year-old woman had recurrent episodes of fully reversible transient monocular blindness accompanied by ipsilateral headache for 15 months. The patient's neuroimaging and cardiac and ophthalmologic evaluations were normal. With a diagnosis of retinal migraine, her symptoms remitted in response to prophylactic treatment with topiramate and propranolol for 8 months. Three months after discontinuation of medications, transient monocular blindness recurred. High-resolution vessel wall magnetic resonance imaging revealed enhancement of the ipsilateral orbital vessels. Isolated orbital vasculitis was diagnosed. Complete remission of transient monocular blindness was achieved after steroid pulse therapy. DISCUSSION: Isolated orbital vasculitis should be considered in differential diagnosis of recurrent transient monocular blindness and ipsilateral headache. High-resolution vessel wall magnetic resonance imaging can be helpful for the diagnosis.

Incidence and timing of recurrence of optic neuritis.

PURPOSE: To describe the incidence and timing of recurrence in patients with optic neuritis (ON). METHODS: Medical documents of adult patients with ON were retrospectively reviewed. The incidence and timing of recurrence of an ON episode were analyzed. RESULTS: One hundred eleven patients with ON were included in this study. Their mean follow-up duration was 4.1 ± 3.1 years. Seven relapses occurred after intravenous methylprednisolone treatment. The estimated cumulative incidence of recurrence in either eye was 26% at 1 year, 33% at 3 years, 37% at 5 years, and 50% at 10 years after the first episode of ON. If there was no recurrence until 6 months after the first episode of ON, the next 5-year recurrence-free survival probability was 67%. If there was no recurrence until 1 year, the next 5-year survival probability was 72%. If there was no recurrence until 2 years, the next 5-year survival probability was 81%. Relapse within 1 month and the presence of neuromyelitis optica-immunoglobulin G were factors that increased the recurrence rate over time. CONCLUSIONS: We evaluated the incidence and timing of the recurrence in patients with ON after the first episode. Lower probability of recurrence was observed in patients with longer recurrence-free follow-up period. However, monitoring for recurrence is needed even in patients with a single episode of ON due to the increasing tendency of the estimated cumulative incidence of recurrence over many years.