Immune non-interference and safety study of Vi-DT typhoid conjugate vaccine with a measles, mumps and rubella containing vaccine in 9-15 months old Nepalese infants.

BACKGROUND: Typhoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9-15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine. METHODS: This was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9-15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination. RESULTS: Using the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were -2.73% (-8.85, 3.38), -3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the -10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events . CONCLUSIONS: Results indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid.

Changes of retinal structure and visual function in patients with demyelinating transverse myelitis.

PURPOSE: To identify the retina-structural and visual-functional alterations in the patients with aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein-associated disease (MOGAD), and multiple sclerosis (MS) patients, all of whom had demyelinating transverse myelitis (TM) without optic neuritis (ON). METHODS: In this retrospective cross-sectional study, we reviewed the medical records of 97 patients, including 23 with AQP4-ON, 13 with AQP4-TM, 32 with MOG-ON, 3 with MOG-TM, 13 with MS-ON, and 13 with MS-TM. We measured the thickness of the retinal nerve fiber layer (RNFL) and the ganglion cell layer-inner plexiform layer (GCIPL) using optical coherence tomography to evaluate structural changes and compared these parameters with those of an age-matched healthy control. Functional outcomes were measured as visual acuity and mean deviation in visual field test. RESULTS: Mean RNFL and GCIPL thicknesses in all of the patients with TM were lower relative to the healthy control, while visual function was well preserved. Among the TM patients, RNFL thickness did not vary significantly among the groups, whereas GCIPL thickness in AQP4-TM and MS-TM was significantly lower than that in MOG-TM. All three TM groups showed significant mean RNFL reduction compared with the healthy control, whereas mean GCIPL thinning was evident only in AQP4-TM and MS-TM, not in MOG-TM. CONCLUSION: Patients with demyelinating TM incur retina-microstructural damage that varies by specific disease entity. Damage is distinct in AQP4-IgG-positive NMOSD and MS, but it is not so severe as to cause functional damage.

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age.

Trial Design: Phase 3, randomized, controlled, multicenter, equivalence trial. Methods: Recruitment of participants occurred between 04Februray2020 and 15July2020 at four centers in the Philippines: University of the East - Ramon Magsaysay Memorial Medical Center Inc., Quezon City; University of Philippines Manila - National Institute of Health, Ermita Manila; Asian Hospital and Medical Center, Metro Manila, Philippines Study; and Medical Research Unit, Tropical Disease Foundation, Makati City, Metro Manila, Philippines. Participants: 1800 adults and children 6-months to 45-years of age. Interventions: Participants received a single injection of multidose (MD) or single dose (SD) Vi-DT as test vaccines or meningococcal conjugate vaccine as a comparator. Objective: To evaluate immune equivalence of SD and MD formulations of Vi-DT, and to assess the safety of both formulations compared with comparator vaccine. Outcome Measurement: Blood draw for immunogenicity was performed at baseline prior to vaccine receipt and at four weeks after vaccination for a subset of participants to determine anti-Vi IgG geometric mean titers (GMT) and seroconversion rates. The primary outcome was comparison of anti Vi-IgG seroconversion and GMT between the two formulations of Vi-DT at 4 weeks following vaccine administration. Immune equivalence of MD and SD formulations was confirmed when the two-tailed 95% confidence interval (CI) of the GMT ratio is within [0.67, 1.5] at a two-sided significance level of 0.05. All participants were followed for safety events for six months after vaccine administration. Randomization: Participants were randomized to receive SD Vi-DT, MD Vi-DT, or meningococcal conjugate vaccines in 2.5:2.5:1 allocation ratio. Blinding: Study participants and observers were blinded to treatment assignment. Findings: Immune equivalence of SD (n=252) and MD (n=247) formulations was confirmed by anti-Vi IgG GMT ratio of 1.14 (95%CI: 0.91, 1.43) with respective GMTs in the MD and SD groups of 640.62 IU/mL (95%CI: 546.39, 751.11) and 562.57 IU/mL (95%CI: 478.80, 661.00) (p=0.259). Similarly, anti-Vi IgG seroconversion rate difference between the two formulations of ‒0.43% (95%CI: -4.42, 3.56) confirmed immune equivalence with corresponding seroconversion rates of 98.38% (95%CI: 95.91, 99.37) and 98.81% (95%CI: 96.56, 99.59) in MD and SD Vi-DT formulations, respectively (p=0.722). Both formulations of Vi-DT had a satisfactory safety profile - all five serious adverse events reported during the study were unrelated to the investigational product. Interpretation: The MD and SD formulations of Vi-DT elicited robust and equivalent immune responses following one dose vaccination, and both formulations demonstrated a favorable safety profile. Trial Registration: ClinicalTrials.gov: NCT04204096. Funding: This study was funded by the Bill & Melinda Gates Foundation (OPP 1115556).

The microbiomes of the eyelid and buccal area of patients with uveitic glaucoma.

BACKGROUND: The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. METHODS: The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. RESULTS: In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e-6 and 1.55e-7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e-12 and 2.55e-6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e-17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e-8). CONCLUSIONS: The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.

Immune persistence and response to booster dose of Vi-DT vaccine at 27.5 months post-first dose.

Vaccination with typhoid conjugate vaccines (TCV) is a major part of typhoid prevention. However, little is known about long-term immune persistence following vaccination with TCVs. In this phase-2, randomized double-blind trial (NCT03527355), 285 children aged 6-23 months were randomized to one of three groups: (1) the group that received a first dose of Vi polysaccharide conjugated to diphtheria-toxoid (Vi-DT) vaccine followed by an "early booster" at 24 weeks, (2) the group that which received a first dose of Vi-DT followed by a "late booster" at 96 or 110 weeks, and (3) comparator group. Safety and immunogenicity of anti-Vi IgG GMTs were assessed at weeks 0, 4, 24, 28, 60, 96, 110, and 114 since the first dose. Here, we describe persistence of immune responses at weeks 60, 96, 110, and 114 post first dose. The anti-Vi IgG seroconversion rate after 27.5 months of follow-up was 88.16% (95% CI: 79.00, 93.64) in late-booster and 94.76% (95% CI: 86.91, 97.88) in early booster Vi-DT groups (p = 0.081). Whereas anti-Vi IgG GMTs were significantly higher in the early booster group (11.95 [95% CI: 9.65, 14.81]) than prebooster GMTs in the late booster group (5.50 [95% CI: 4.44, 6.80], p < 0.0001). GMT in the late booster group significantly increased to 351.76 (95% CI: 265.01, 466.93) (p < 0.0001) when measured 4 weeks after they received their "late-booster" shot. In conclusion, late booster dosing with Vi-DT at 27.5 months post first dose was safe and elicited robust anti-Vi IgG immune responses. Anti-Vi IgG seroconversion rates were persistently comparable in early and late-booster Vi-DT groups.

Differences in the eyelid and buccal microbiome between open-angle glaucoma and uveitic glaucoma.

PURPOSE: Microbiomes have immunoregulatory functions and may be involved in the pathophysiology of eye diseases. However, the effects of microbiomes on uveitic glaucoma (UG) and open-angle glaucoma (OAG) have not been sufficiently investigated. This study analysed differences in eyelid and buccal microbiomes between UG and OAG using metagenomic technology. METHODS: Eyelid and buccal specimens were collected from 34 UG and 62 OAG patients. The taxonomic composition of the microbiome was determined via 16S rRNA gene sequencing, operational taxonomic unit analysis and diversity analysis. Differential gene expression analysis (DEG) and principal component analyses (PCoA) determined taxon differences between the microbiomes of the UG and OAG patients. Subgroup analysis according to age and baseline IOP was performed. RESULTS: There was no significant difference in alpha-diversity between the microbiomes of UG and OAG patients. Further, PCoA revealed no differences in eyelid microbiome between the UG and OAG groups, but significant differences were found in buccal microbiome between the groups, especially in a subgroup of OAG patients with normal IOP. DEG analysis of the eyelid microbiome revealed various taxa differences, including the enrichment of Rhodococcus in UG samples over OAG samples. Taxa such as Lactobacillus and Proteus were significantly depleted (q-value = 9.98e-6 and q-value = 1.38 × 10-4 , respectively) in the buccal microbiome of UG patients, whereas Enterococcus was enriched (q-value = 5.26e-5 ). CONCLUSIONS: This study showed that the buccal microbiome in UG differs from that in OAG; reduced Lactobacillus was observed in UG. These results suggest that apart than OAG, microbiome composition may be a factor in the pathogenesis of UG.

Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

BACKGROUND: Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country. METHODS: We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to <2 years, 2 years to <18 years, and 18 years to 45 years), into one of four groups (A-D). Participants in groups A-C received a single dose (25 µg; 0·5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 µg; 0·5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A-C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and (2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97·5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A-C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of -10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99·17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0·67 and 1·50, which is the predefined equivalence margin recommended by WHO. The co-primary immunogenicity endpoints were assessed in all randomised participants who had received their assigned vaccine and had completed at least one post-baseline immunogenicity assessment. Safety was descriptively summarised by group and age strata, and was assessed in all participants who had received one dose of the investigational vaccine. The trial is registered with ClinicalTrials.gov, NCT03933098. FINDINGS: Between Nov 20, 2019, and March 10, 2020, 1854 individuals were screened, of whom 1800 were enrolled and randomly assigned to groups A-D (450 participants in each group). 1786 (99·2%; 443 in group A, 450 in group B, 447 in group C, and 446 in group D) were included in the immunogenicity assessments at 4 weeks post vaccination, and all 1800 participants were included in the safety analysis. In the immunogenicity analysis, the anti-Vi-IgG seroconversion rate in all age strata was 99·33% (97·5% CI 98·61 to 99·68; 1331 of 1340 participants) in Vi-DT vaccine groups A-C and 98·88% (97·10 to 99·57; 441 of 446) in Vi-TT vaccine group D. The difference in seroconversion rates between Vi-DT vaccine groups A-C combined versus Vi-TT group D was 0·47% (97·5% CI -0·68 to 1·61), indicating non-inferiority of the Vi-DT vaccine. Anti-Vi-IgG GMT ratios at 4 weeks post-vaccination were 1·02 (99·17% CI 0·85 to 1·22) for lot 1 versus lot 2, 1·02 (0·85 to 1·23) for lot 1 versus lot 3, and 1·01 (0·84 to 1·21) for lot 2 versus lot 3, indicating lot-to-lot equivalence according to the predefined, WHO-recommended equivalence margin. The proportion of participants reporting adverse events was similar between Vi-DT vaccine groups A-C and Vi-TT vaccine group D; 260 (19·3%) of 1350 participants in Vi-DT vaccine groups A-C and 115 (25·6%) of 450 in Vi-TT vaccine group D reported solicited adverse events within 7 days after vaccination, and 208 (15·4%) in Vi-DT vaccine groups A-C and 76 (16·9%) in Vi-TT vaccine group D reported unsolicited adverse events within 4 weeks after vaccination. Seven serious adverse events (four [0·3%] participants in Vi-DT vaccine groups A-C and three [0·7%] in Vi-TT vaccine group D), including one death in the Vi-TT vaccine group, were reported during the 24-week follow-up period, none of which were considered related to the investigational product. INTERPRETATION: When administered as a single dose, the Vi-DT test vaccine was safe, immunogenic, and non-inferior to the Vi-TT vaccine at 4 weeks post vaccination. Equivalent immunogenicity of the three lots of Vi-DT vaccine was also shown, supporting the manufacturing process of this vaccine. Once prequalified by WHO, this vaccine could be an option for purchase by UN agencies. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATION: For the Nepali translation of the abstract see Supplementary Materials section.

Analysis of oral microbiome in glaucoma patients using machine learning prediction models.

Purpose: The microbiome is considered an environmental factor that contributes to the progression of several neurodegenerative diseases. However, the association between microbiome and glaucoma remains unclear. This study investigated the features of the oral microbiome in patients with glaucoma and analyzed the microbiome biomarker candidates using a machine learning approach to predict the severity of glaucoma. Methods: The taxonomic composition of the oral microbiome was obtained using 16S rRNA gene sequencing, operational taxonomic unit analysis, and diversity analysis. The differentially expressed gene (DEG) analysis was performed to determine the taxonomic differences between the microbiomes of patients with glaucoma and the control participants. Multinomial logistic regression and association rule mining analysis using machine learning were performed to identify the microbiome biomarker related to glaucoma severity. Results: DEG analysis of the oral microbiome of patients with glaucoma revealed significant depletion of Lactococcus (P = 3.71e-31), whereas Faecalibacterium was enriched (P = 9.19e-14). The candidate rules generated from the oral microbiome, including Lactococcus, showed 96% accuracy for association with glaucoma. Conclusions: Our findings indicate microbiome biomarkers for glaucoma severity with high accuracy. The relatively low oral Lactococcus in the glaucoma population suggests that microbial dysbiosis could play an important role in the pathophysiology of glaucoma.

Differences in the eyelid and buccal microbiome of glaucoma patients receiving long-term administration of prostaglandin analog drops.

PURPOSE: To investigate the differences in the eyelid and buccal microbiomes between patients receiving long-term prostaglandin analogs for open-angle glaucoma (PG-OAG) and naïve-OAG patients by using metagenomics. METHODS: Eyelid and buccal samples were collected from 30 PG-OAG and 32 naïve-OAG patients. The taxonomic composition of the microbiome was obtained via 16S rRNA gene sequencing, operational taxonomic unit analysis, and diversity analysis. Differential gene expression analysis (DEG) and Bland-Altman (MA) plots were used to determine taxon differences between the microbiomes of PG-OAG and naïve-OAG patients. RESULTS: The eyelid microbiome showed marginally significant differences, while the alpha-diversity of the buccal microbiome showed significant differences between PG-OAG and naïve-OAG patients. However, the beta-diversity of both eyelid and buccal microbiomes was higher in PG-OAG patients than in naïve-OAG patients. The MA plot showed cluster differences in the eyelid microbiome. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Azomonas, Pseudomonas, and Granulicatella in PG-OAG patients over naïve-OAG patients, as well as significant depletion of Delftia and Rothia. In the buccal microbiome in PG-OAG patients, taxa such as Rikenella and Stenotrophomonas were significantly enriched. CONCLUSION: Our findings suggest that the eyelid microbiome differs between PG-OAG and naïve-OAG patients, raising concerns regarding the eyelid environment in patients receiving these drugs. The overexpressed microbiome in the eyelid area suggests that microbiota may change after the administration of glaucoma medications in OAG.

Analysis of factors affecting visual field recovery following surgery for pituitary adenoma.

PURPOSE: To analyze the factors influencing visual field recovery in patients with pituitary adenoma following surgical treatment. METHODS: We retrospectively reviewed 144 eyes of 72 patients with pituitary adenoma who had been followed up for more than 6 months following surgery between January 2016 and December 2019. Pre and postoperative visual acuity, visual field test and retinal nerve fiber layer (RNFL) thickness were investigated. We defined recovery of visual field defects as being an improvement in mean deviation (MD) of 2 dB or more. RESULT: The average age of the 72 patients (144 eyes) was 51.94 ± 14.69 years, making for 37 patients in the recovery group and 35 patients in the non-recovery group. Preoperative MD, pattern standard deviation (PSD), and visual field indexes (VFI) were negatively correlated to postoperative MD, PSD and VFI changes and positively correlated to postoperative MD, PSD, and VFI values. Using multiple regression analysis, a shorter duration of symptoms (Odds ratio [OR], 0.990; p = 0.033), higher preoperative MD values (OR, 0.871; p = 0.025), and thicker temporal RNFL (OR, 1.068; p = 0.048) were associated with a visual field recovery following surgery. CONCLUSIONS: The prognosis for visual field recovery is favorable for patients who have a short period from symptom onset to surgery, a higher MD value of preoperative VF, and a thicker peripapillary temporal RNFL thickness. Therefore, the preoperative MD, temporal RNFL thickness, and the symptom period can be predictive variables affecting postoperative visual field recovery.

Relationship between intraocular pressure and parameters of obesity in ocular hypertension.

AIM: To evaluate the correlation between intraocular pressure (IOP) and various obesity-related health factors in patients with ocular hypertension in Korea. METHODS: A total of 40 850 subjects underwent age, sex, body weight, and height assessments and automated multiphasic tests, including non-contact tonometry, automated perimetry, fundus photography, systolic/diastolic blood pressure measurement, and evaluation of obesity-related health parameters such as obesity index, body mass index (BMI), a body shape index (ABSI), and waist-to-height ratio (WtHR). Subjects were divided into ocular hypertension group and normal IOP group according to IOP after matching of age and sex. RESULTS: Of 40 850 participants, 1515 (3.7%) had ocular hypertension, and 1515 with normal IOP were selected as controls using propensity score matching. The mean IOP of control group was 15.3±2.3 mm Hg, compared with 23.3±1.6 mm Hg in ocular hypertension group. Height, obesity index, BMI, and WtHR in the ocular hypertension group were significantly higher than in the normal IOP group (P<0.001, P<0.001, P=0.009, P=0.002). IOP of ocular hypertension was positively correlated with obesity index (P=0.027) and BMI (P=0.016), whereas IOP of control was positively correlated with blood pressure (P<0.001, P=0.002), obesity index (P<0.001), BMI (P<0.001), and WHtR (P=0.002). Systolic blood pressure (ß=0.022, P<0.001) and body weight (ß=0.016, P=0.02) were precursors of IOP in normal subjects, but sex (male; ß=-0.231, P=0.008) and obesity index (ß=-0.007, P=0.017) were precursors of ocular hypertension according to multiple regression analysis. CONCLUSION: Among various obesity-related health parameters, obesity index is the best indicator for further increase in IOP in ocular hypertension group.

Comparison between optic neuritis associated with antibody against myelin oligodendrocyte glycoprotein and presumed idiopathic optic perineuritis.

BACKGROUND: The aim of this study was to determine important clinical and radiological features that aid in distinguishing presumed idiopathic optic perineuritis (OPN) from optic neuritis (ON) associated with antibody against myelin oligodendrocyte glycoprotein (MOG-Ab). METHODS: This retrospective, case-control study recruited patients with MOG-Ab-associated ON from 2011 through 2018 and idiopathic OPN from 2009 through 2011. The presence of MOG-Ab was not investigated in idiopathic OPN, because MOG-Ab testing was not available until 2011. The clinical and radiological features and the disease course were compared between the two patient groups. RESULTS: A total of 48 patients with MOG-Ab-associated ON were identified. These included 15 patients showing optic nerve sheath enhancement (ONSE) and 33 with only optic nerve enhancement. Ocular pain with ocular movement and optic disc swelling were more common in patients with ONSE, who also exhibited a poorer initial visual acuity than did those without ONSE. However, the response to steroid treatment, incidence of relapse after steroid treatment, and visual outcome at the last visit were similar between subgroups. The clinical and radiological features and treatment outcome were similar between these patients with OPN and patients with MOG-Ab-associated ON with ONSE. On the other hand, the clinical features of MOG-Ab-associated ON without ONSE differed from those of idiopathic OPN. CONCLUSION: Our findings showed a substantial proportion of ONSE in patients with MOG-Ab-associated ON. In view of the similarities between these patients and patients with OPN, MOG-Ab testing should be performed in all patients with idiopathic OPN.

Comparison of conjunctival vascularity changes using optical coherence tomography angiography after trabeculectomy and phacotrabeculectomy.

PURPOSE: To compare bleb vascularity changes using optical coherence tomography angiography (OCT-A) between mitomycin-C (MMC)-augmented trabeculectomy and phacotrabeculectomy and to determine whether bleb vascularity measurements during preoperative and early postoperative periods could act as surrogate parameters to predict surgical outcomes. METHODS: We retrospectively reviewed data for 72 eyes from 72 glaucoma patients who underwent MMC-augmented trabeculectomy with/without cataract surgery. Bleb area scans were obtained using OCT-A during the preoperative period; 1, 2, 4, and 6 weeks postoperatively; and 2, 4, and 6 months postoperatively. For conjunctival vascularity analysis, a semi-automated program was used to calculate color and brightness densities of the selected area. RESULTS: Color and brightness densities were decreased in the trabeculectomy group during all periods but not in the phacotrabeculectomy group at 4 and 6 weeks, as well as 2, 4, and 6 months postoperatively. Color and brightness densities were significantly higher in the phacotrabeculectomy group than in the trabeculectomy group after 6 weeks and 2, 4, and 6 months postoperatively. A Kaplan-Meier survival graph indicated that intraocular pressure differed according to glaucoma type but not surgery type. Logistic regression analysis revealed that brightness density 1 week postoperatively was correlated with reoperation. CONCLUSIONS: Changes in conjunctival vascularity density measured by OCT-A differed according to the surgical method. Following trabeculectomy with MMC, brightness density 1 week postoperatively may be a predictive index for surgical outcomes.

Arteritic Anterior Ischemic Optic Neuropathy Associated with Giant-Cell Arteritis in Korean Patients: A Retrospective Single-Center Analysis and Review of the Literature.

BACKGROUND AND PURPOSE: The aim of this study is to report the relative incidence of arteritic anterior ischemic optic neuropathy (AAION) associated with giant-cell arteritis (GCA) in a single-center and evaluate the clinical features of AAION in Korean patients. METHODS: The medical records of patients with presumed AION who visited our hospital from January 2013 to August 2018 were examined retrospectively. The patients were divided into two groups: AAION associated with GCA, and non AION (NAION). We additionally reviewed the literature and identified all cases of AAION in Korean and Caucasian patients. We evaluated the clinical data including the initial and final best-corrected visual acuities, fundus photographs, visual field tests, fluorescein angiography, and contrast-enhanced MRI, and compared the data with those for Caucasian patients in the literature. RESULTS: Of the 142 patients with presumed AION, 3 (2.1%) were diagnosed with AAION and 139 (97.9%) were diagnosed with NAION. Seven Korean patients with AAION associated with GCA were identified in our data and the literature review. We found no difference in any clinical features other than laterality: four of the seven Korean patients had bilateral involvement. Moreover, the optic nerve sheath was enhanced in two of our Korean patients. CONCLUSIONS: AAION associated with GCA is a very rare condition compared to NAION in Korea. However, GCA should be considered in all cases of ischemic optic neuropathy because AAION is associated with poor visual outcome, and sometimes presents bilaterally.

K-means Data Clustering with Memristor Networks.

Memristor-based neuromorphic networks have been actively studied as a promising candidate to overcome the von-Neumann bottleneck in future computing applications. Several recent studies have demonstrated memristor network's capability to perform supervised as well as unsupervised learning, where features inherent in the input are identified and analyzed by comparing with features stored in the memristor network. However, even though in some cases the stored feature vectors can be normalized so that the winning neurons can be directly found by the (input) vector-(stored) vector dot-products, in many other cases, normalization of the feature vectors is not trivial or practically feasible, and calculation of the actual Euclidean distance between the input vector and the stored vector is required. Here we report experimental implementation of memristor crossbar hardware systems that can allow direct comparison of the Euclidean distances without normalizing the weights. The experimental system enables unsupervised K-means clustering algorithm through online learning, and produces high classification accuracy (93.3%) for the standard IRIS data set. The approaches and devices can be used in other unsupervised learning systems, and significantly broaden the range of problems a memristor-based network can solve.

Anti-scarring effects of butaprost on human subconjunctival Tenon's fibroblasts.

AIM: To investigate the toxicity of the E-prostanoid 2 (EP2) receptor agonist, butaprost against human subconjunctival (Tenon's capsule) fibroblasts, and to determine the underlying mechanism. METHODS: We isolated Tenon's fibroblasts from the subconjunctival area of healthy subjects and evaluated the types of EP receptors expressed using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The toxicity of butaprost against the fibroblasts was evaluated using methyl thiazolyl tetrazolium and lactic dehydrogenase assays. The inhibition of conjunctival fibroblast proliferation by butaprost was assessed by measuring α-actin levels. The underlying mechanism was assessed by measuring intracellular cyclic adenosine monophosphate (cAMP) levels. Intergroup differences were statistically analyzed using an independent t-test. Densitometry of the Western blot bands was performed using the Image J software. RESULTS: Quantitative real-time RT-PCR revealed that the fibroblast EP2 receptor levels were higher than those of the other EP receptors. Butaprost did not show toxicity against Tenon's tissue, but inhibited conjunctival fibroblast proliferation by reducing collagen synthesis. EP2 receptor activation enhanced the cAMP cascade, which might be an important mechanism underlying this effect. CONCLUSION: Butaprost effectively reduces the subconjunctival scarring response. Given the significance of wound healing modulation in blebs, butaprost's inhibitory effect on subconjunctival Tenon's fibroblasts may be beneficial in managing postoperative scarring in glaucoma surgery.

Experimental Demonstration of Feature Extraction and Dimensionality Reduction Using Memristor Networks.

Memristors have been considered as a leading candidate for a number of critical applications ranging from nonvolatile memory to non-Von Neumann computing systems. Feature extraction, which aims to transform input data from a high-dimensional space to a space with fewer dimensions, is an important technique widely used in machine learning and pattern recognition applications. Here, we experimentally demonstrate that memristor arrays can be used to perform principal component analysis, one of the most commonly used feature extraction techniques, through online, unsupervised learning. Using Sanger's rule, that is, the generalized Hebbian algorithm, the principal components were obtained as the memristor conductances in the network after training. The network was then used to analyze sensory data from a standard breast cancer screening database with high classification success rate (97.1%).

Does Glaucoma Share Common Pathogenesis with Branch Retinal Vein Occlusion?

BACKGROUND: To evaluate the observed prevalence and the optic nerve head (ONH) characteristics of normal tension glaucoma (NTG)-suspect eyes in branch retinal vein occulusion (BRVO) eyes in Korean population. METHODS: This was a retrospective observational study. We investigated 445 BRVO eyes that were diagnosed in the retina clinic of Samsung Medical Center between March 2005 and December 2011. The observed prevalence of NTG-suspect in BRVO eyes was evaluated compared to the previous population based study. In addition, NTG-suspect cases in BRVO were divided into three groups based on the characteristics of optic disc morphology. RESULTS: In 445 BRVO eyes, 30 eyes were excluded from the present study. In 415 BRVO eyes, 4.3% (18 eyes) (95% confident interval [CI], 2.4-6.3%) were diagnosed with suspect glaucoma and this is not significantly different from the result in the general Korean population (P = 0.09). We classified the NTG-suspect eyes into three groups such as disc rim notching and thinning type (Group 1; 55.6%), optic cup-sited hemorrhage type (Group 2; 16.7%) and disc rim thinning and pallor type (Group 3; 27.8%). NTG-suspect in the fellow eye were only found in group 1 (80%) and group 2 (67%), but not in group 3 (P = 0.01). CONCLUSIONS: BRVO and glaucoma seem to have no common vascular pathogenesis in consideration of the prevalence of NTG-suspect in BRVO eyes compared to general Korean population.

Intracranial fibromuscular dysplasia presenting as various ocular manifestations.

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that mainly affects renal, extracranial carotid, and vertebral arteries. Intracranial FMD is uncommon unlike extracranial or renal FMD, and the primary manifestation of intracranial FMD is intracranial aneurysm. We report an unusual case of intracranial FMD showing various ocular manifestations, including central retinal artery occlusion, transient monocular blindness, and oculomotor nerve palsy without renal involvement.