Intraocular foreign body: Characteristics, visual outcomes, and predictive values of ocular trauma score.

Introduction: Retained intraocular foreign body (IOFB) remains an important cause of acquired visual impairment. The visual prognosis following treatments for eyes with retained IOFB was observed to be distinct from other mechanisms of open globe injury due to the specific nature and associated circumstances. This study evaluated the risk behaviors, visual results, and predictive values of Ocular Trauma Score (OTS) in determining visual outcomes in patients with IOFB that were not related to terrorism. Methods: Medical records of patients who underwent surgical interventions between January 2015 and December 2020 were retrospectively reviewed. Results: A total of one hundred and sixty-one patients (162 eyes) were recruited. The patients had a mean (standard deviation) age of 47.6 (14.0) years with working male predominance (93.2%). The majority of patients were injured by activities related to grass trimming (63.4%) and metallic objects were the main materials causing injuries (75.7%). Following treatments, the proportion of eyes having vision worse than 20/400 decreased from 126 eyes (77.8%) to 55 eyes (33.9%) at final visit. Ocular trauma score (OTS) had a high potential prediction for final vision in eyes in OTS categories 4 and 5. However, the discordance of final visual acuity distribution was observed in some subgroups of eyes in OTS categories 1 to 3. Conclusion: This study highlights the significance of IOFB related eye injuries in a tertiary care setting. Decision making on treatments should be carefully considered, particularly in eyes in lower OTS categories, in light of a rise in the proportion of patients who experience improved vision after IOFB removal.

Metabolic Profiling of Rheumatoid Arthritis Neutrophils Reveals Altered Energy Metabolism That Is Not Affected by JAK Inhibition.

Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However, clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors have been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n = 6) and people with RA (n = 7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200 ng/mL) for 2 h. Metabolites were extracted, and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models showed a divergent metabolic pattern in RA neutrophils compared to HC at 0 h (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p < 0.05). Bacterial killing was not impaired by JAK inhibitors, indicating that the effect of JAK inhibitors on neutrophils can inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.

Reference Database of Inner Retinal Layer Thickness and Thickness Asymmetry in Healthy Thai Adults as Measured by the Spectralis Spectral-Domain Optical Coherence Tomography.

INTRODUCTION: The study aimed to determine a reference database of the thickness and intraocular thickness asymmetry of total retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in healthy Thai subjects measured by the Spectralis spectral-domain optical coherence tomography. METHODS: This cross-sectional study recruited the healthy subjects age ≥18 years, having spherical refraction within ±6 diopters and cylindrical refraction ±3 diopters, from a hospital's personnel and the people visiting the ophthalmology department. Only 1 eye of each subject was randomly selected for an analysis. Macular images were obtained using posterior pole thickness scan protocol over a 24° × 24° area at the center of the fovea. The automated retinal thickness segmentation values of total retina and three inner retinal layers were calculated for the mean and the mean intraocular thickness difference between superior and inferior retinal hemispheres. The influence of age, gender, and axial length on thickness and thickness asymmetry of individualized retinal layer was evaluated. RESULTS: 252 subjects were included in study with a mean (SD) age of 46.7 (15.8) years, and 120 (47.6%) were males. According to the Early Treatment Diabetic Retinopathy Study map, the inner ring area was the thickest location of the total retina (range; 326.0-341.5 µm), GCL (range; 47.7-52.7 µm), and IPL (range; 39.9-42.1 µm), whereas the thickest location of RNFL was at the outer ring area (range; 18.8-47.5 µm). For posterior pole intraocular thickness asymmetry, the greatest mean ± SD difference was observed for total retina (9.0 ± 2.2 µm), followed by RNFL (9.9 ± 3.2 µm) and GCL (2.7 ± 0.6 µm), and the lowest mean difference was noted for IPL (2.4 ± 0.5 µm). The thickness and thickness asymmetry of each retinal layer were variably influenced by age, gender, and axial length; however, these factors had a minimal influence on the thickness asymmetry maps of GCL and RNFL. CONCLUSION: The reference database of the macular thickness and thickness asymmetry from this study would be beneficial in determining physiologic variations of the OCT parameters in the healthy Thai population.

Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury.

Ferroptosis is a recently recognized form of nonapoptotic cell death that is triggered by reactive oxidative species (ROS) due to iron overload, lipid peroxidation accumulation, or the inhibition of phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Recent studies have reported that ferroptosis plays a vital role in the pathophysiological process of multiple systems such as the nervous, renal, and pulmonary systems. In particular, the kidney has higher rates of O2 consumption in its mitochondria than other organs; therefore, it is susceptible to imbalances between ROS and antioxidants. In ischemia/reperfusion (I/R) injury, which is damage caused by the restoring blood flow to ischemic tissues, the release of ROS and reactive nitrogen species is accelerated and contributes to subsequent inflammation and cell death, such as ferroptosis, as well as apoptosis and necrosis being induced. At the same time, I/R injury is one of the major causes of acute kidney injury (AKI), causing significant morbidity and mortality. This review highlights the current knowledge on the involvement of ferroptosis in AKI via oxidative stress.

Prevalence of symptomatic dry eye disease with associated risk factors among medical students at Chiang Mai University due to increased screen time and stress during COVID-19 pandemic.

Dry eye disease (DED) is one of the most common ophthalmological disorders, resulting from several systemic and ocular etiologies including meibomian gland dysfunction (MGD). During the COVID-19 pandemic, medical students are among the high-risk group for DED, mainly due to the increasing use of a visual display terminal (VDT) for online lectures and psychological stress from encountering several changes. Our study aimed to explore the prevalence of DED using the symptom-based definition and potential risk factors in medical students. This is a prospective cross-sectional study that included medical students at Chiang Mai University between November 2020 and January 2021. All participants were assessed using the Ocular Surface Disease Index (OSDI) questionnaire, the Thai version of the 10-Item Perceived Stress Scale-10 (T-PSS-10), the LipiView® II interferometer, and an interview for other possible risk factors. Overall, 528 participants were included in the study; half of the participants were female. The prevalence of DED was 70.8%. In the univariate analysis, female sex, contact lens wear, and T-PSS-10 stress scores were significantly higher in the DED group (P = 0.002, 0.002, and <0.001, respectively). Moreover, participants with severe DED were likely to have higher meibomian gland tortuosity but not statistically significant. In the multivariate analysis, contact lens use and T-PSS-10 score were significant risk factors associated with the severity of DED. In conclusions, the prevalence of DED in medical students was as high as 70.8%. Contact lens use and psychological stress evaluated using the T-PSS-10 questionnaire had a significant correlation with a risk of DED. Female gender and duration of VDT use were also associated. Most of the risk factors were modifiable and may be used as initial management in patients with DED.

Visual acuity and anatomical changes following vitrectomy for epiretinal membrane foveoschisis: a case series.

PURPOSE: To evaluate the visual outcome and macular anatomic structures on spectral-domain optical coherence tomography (SD-OCT) of patients with epiretinal membrane (ERM) foveoschisis who underwent vitrectomy. METHODS: A retrospective cohort, interventional, case series. PARTICIPANTS: Fourteen patients (14 eyes) with central vision loss from an ERM foveoschisis underwent vitrectomy at Chiang Mai University Hospital from 2017 to 2018 and had a follow-up period of 12 months. INTERVENTIONS: The 23G vitrectomy with ERM and internal limiting membrane (ILM) peeling was performed by a single surgeon. MAIN OUTCOMES: Best-corrected visual acuity (BCVA) and anatomic appearance on SD-OCT were assessed at the time of preoperative evaluations and post-operative follow-ups at 1, 3, 6, and 12 months. RESULTS: Fourteen patients with a mean (SD) age of 67.9 (7.9) years and a mean (SD) visual acuity (VA) of 0.6 (0.1) LogMAR units were included in this study. Significant VA improvements were observed at the 3-month (0.43 (0.14) LogMAR unit), 6-month (0.45 (0.16) LogMAR unit) and 12-month (0.37 (0.21) LogMAR unit) post-operative visits compared to baseline, all with P-values < 0.001. At month 12, there were vision improvements of ≥3 lines in 8 (57.2%) patients, vision improvements of 1 or 2 lines in 2 (14.3%) patients, vision remained at the same line of pre-operation in 3 (21.4%) patients, and vision decreased by 1 line in 1 (7.1%) patient. Regarding the anatomical outcomes, 13 (92.9%) patients achieved anatomical foveal restoration, while one had persistent intraretinal schisis at the 12-month follow-up. The median time to achieve a foveal restoration was 3 months. No significant visual impairments were observed post-operatively. CONCLUSION: In patients with central vision loss from ERM foveoschisis, vitrectomy with ILM stripping tended to improve both visual and anatomical outcomes.

Risk factors and outcomes of post-traumatic endophthalmitis: a retrospective single-center study.

BACKGROUND: To describe the epidemiology, characteristics, risk factors, and outcomes of post-traumatic endophthalmitis. MAIN BODY: Medical records of consecutive open globe injury patients admitted and primarily treated between January 2006 and December 2016 were retrospectively reviewed. Patients were defined as having or not having associated endophthalmitis. Data of demographics, injury characteristics, clinical presentations, and visual outcomes were collected. The potential risks and significant factors for visual outcomes of post-traumatic endophthalmitis were determined. There were 591 patients included in this study. Among these, 118 patients were clinically diagnosed as having accompanied endophthalmitis. Higher proportions of intraocular foreign body (IOFB) (55.1% vs. 27.3%) and injury related to high-velocity objects (55.9% vs. 32.6%) were noted in patients with endophthalmitis compared to patients without endophthalmitis. Anterior wound location (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1 to 3.7; P = 0.020), presence of IOFB (OR, 1.9; 95% CI 1.2 to 3.0; P = 0.005), and delayed presentation of > 24 h (OR, 3.9; 95% CI 2.3 to 6.4; P < 0.001) were significant risk factors for associated endophthalmitis. Final visual acuity (VA) of the overall population improved significantly from 2.4 (0.6) logMAR to 1.4 (0.1) logMAR, P < 0.001, however, patients in the endophthalmitis group achieved a worse final VA than the non-endophthalmitis group (66.1% vs. 43.5%, P < 0.001). CONCLUSION: High proportions of post-traumatic endophthalmitis patients had subsequent poor visual outcomes. Therefore, safety and protective measurements, especially when performing activities related to high-velocity objects, and the institution of prophylactic antibiotics in high-risk groups should be promptly considered to reduce the incidence.

The Clinical Features and Prognostic Factors for Treatment Outcomes of Dematiaceous Fungal Keratitis over 9 Years at a Tertiary Eye Care in Northern Thailand.

Dematiaceous fungal keratitis is an important etiology of visual loss, particularly in an agricultural society. From a retrospective review of medical records from 2012 to 2020, 50 keratitis cases of cultured-positive for dematiaceous fungi were presented at a tertiary care hospital in Northern Thailand. The study aimed to identify the isolated causative dematiaceous species using the PCR technique and to explore their related clinical features, including treatment prognoses. Sequencing of the amplified D1/D2 domains and/or ITS region were applied and sequenced. Of the 50 dematiaceous fungal keratitis cases, 41 patients were males (82%). In most cases, the onset happened during the monsoon season (June to September) (48%). The majority of the patients (72%) had a history of ocular trauma from an organic foreign body. The most common species identified were Lasiodiplodia spp. (19.35%), followed by Cladosporium spp. and Curvularia spp. (12.90% each). About half of the patients (52%) were in the medical failure group where surgical intervention was required. In summary, ocular trauma from an organic foreign body was the major risk factor of dematiaceous fungal keratitis in Northern Thailand. The brown pigmentation could be observed in only 26%. Significant prognostic factors for medical failure were visual acuity at presentation, area of infiltrate, depth of the lesions, and hypopyon.

Globe rupture: a single-center retrospective study of demographic patterns and outcomes.

Globe rupture is one of the severe mechanisms of eye injury. This study aimed to describe an epidemiologic patterns and visual outcomes of the open globe injury from globe rupture at a tertiary referral centre. Medical records of 167 patients (173 eyes) were retrospectively reviewed. Overall, males were predominant (82%). Road traffic- (26.3%) and work- (23.4%) were the major contributors. However, falling was the main mechanism in the elderly aged over 60 years. At presentation, 91.4% of eyes had initial visual acuity (VA) of worse than 20/200. The mean (SD) VA in logarithm of the minimum angle of resolution (LogMAR) unit at final [1.8 (1.1)] was significantly improved from presenting VA [2.4 (0.6)] (p ˂ 0.001). Predictors for final VA of worse than 20/400 included poor initial VA, presence of relative afferent pupillary defect, and endophthalmitis. In conclusion, this study observed the peak incidence of globe rupture in young teen to early adult patients, with unique characteristics in each age group. Even with significant visual improvement following the treatments, profound visual loss was still a common consequence. Thus, the role of effective prevention along with a multidisciplinary team together with timely and prompt ophthalmic management should be emphasised.

Low-dose Amiodarone Is Safe: A Systematic Review and Meta-analysis.

Amiodarone is commonly used for a variety of arrhythmias and, in some parts of the world, is the only available antiarrhythmic drug (AAD). Yet, amiodarone is known to have a wide range of potential side effects, many of which are dose- and duration-dependent. We sought to study the incidence of side effects leading to the discontinuation of low-dose amiodarone, arbitrarily defined as 200 mg/day or less, and very-low-dose amiodarone, defined as 100 mg/day or less. In this study, literature databases were searched through June 2019. Studies that reported the incidence or prevalence of side effects of amiodarone were included. Effect estimates from individual studies were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. A total of 10 observational cohort studies involving 901 patients were included in the analysis. The pooled estimated incidence of overall side effects for low-dose amiodarone was 0.17 [95% confidence interval (CI): 0.12-0.22]. In addition, the pooled estimated incidence of side effects requiring medication discontinuation was 0.06 (95% CI: 0.03-0.11). As compared with 200 mg/day of amiodarone, the pooled estimated incidence of overall side effects was 0.11 (95% CI: 0.04-0.27), while the incidence of side effects requiring medication discontinuation was 0.02 (95% CI: 0.01-0.06) for the dose of 100 mg/day. In conclusion, very-low-dose amiodarone displays a low incidence of significant side effects requiring medication discontinuation.

Epidemiology and Outcomes Following Open Globe Injury in Agricultural Region, an 11-Year Experience.

PURPOSE: To determine the characteristics and epidemiology of open globe injury (OGI) in a third referral centre over 11 years. METHODS: The study was a retrospective observational study. The medical records of 978 OGI cases (a total of 998 eyes), admitted to Chiang Mai University Hospital, Thailand from January 2006 to December 2016, were reviewed. RESULTS: The mean age (SD) of patients was 39.1 (17.5) years. Patients were predominantly male (867, 88.7%). The age with the highest incidence of injury ranged from 41 to 60 years, in both genders. Most injuries happened at the workplace (64.8%), with flying objects from electric grass trimmers (23.9%) being the major injury-related mechanism. Penetration injuries were found in 479 eyes (48.0%). In elderly group (aged >60 years), a higher proportion of a globe rupture injuries were observed (13.3%). In general, intraocular foreign body group presented with better initial visual acuity (VA) compared to other injury types (p< 0.001). In all types of injury, final VA was significantly improved after treatment. However, rupture and perforation globe injuries had significantly worse final VA outcomes, compared to penetration and intraocular foreign body injuries (p< 0.001). With multivariable regression analysis, poor initial VA (p< 0.001), type of injury (p= 0.028), positive relative afferent pupillary defect (RAPD) (p< 0.001), and endophthalmitis (p< 0.001) were associated with poor visual outcomes. CONCLUSIONS: Work-related eye injury is a major cause of OGI. Poor initial VA, endophthalmitis, presence of RAPD, and rupture were the predictors for poor final visual outcomes.

A robust intracellular metabolite extraction protocol for human neutrophil metabolic profiling.

Neutrophils are phagocytic innate immune cells that play essential roles in host defence, but are also implicated in inflammatory diseases such as rheumatoid arthritis (RA) where they contribute to systemic inflammation and joint damage. Transcriptomic analysis of neutrophils has revealed significant changes in gene expression in neutrophils activated in vitro by cytokines and in vivo during inflammation in RA. However, there are no reports on the global metabolomic changes that occur as a consequence of this activation. The aim of this study was to establish protocols for the study of changes in the metabolome of human neutrophils using 1H NMR spectroscopy. Sample preparation and spectral analysis protocols were optimised using neutrophils isolated by Ficoll-Paque, with decreased washing steps and inclusion of a heat-shock step to quench metabolite turnover. Cells were incubated ± PMA for 15 min in HEPES-free media and samples were analysed by NMR using a 700 MHz NMR Avance IIIHD Bruker NMR spectrometer equipped with a TCI cryoprobe. Chenomx, Bruker TopSpin and AMIX software were used to process spectra and identify metabolites. Principal Component Analysis (PCA) and signalling pathway analysis was carried out using Metaboanalyst. Cell number and number of scans (NS) were optimised as >3.6 million cells and 512 NS. 327 spectral bins were defined in the neutrophil spectra, of which 287 (87.7%) were assigned to 110 metabolites that included: amino acids, peptides and analogues; carbohydrates, carbonyls and alcohols; nucleotides, nucleosides and analogues; lipids and lipid-like molecules; benzenoids; and other organic compounds. 43 metabolites changed at least 1.5 fold (increase or decrease) after the addition of PMA for 5 or 15 min. Pathway analysis revealed that PMA affected nicotinate and nicotinamide metabolism, aminoacyl-tRNA biosynthesis and glycolysis, suggesting a redirection of glucose metabolism from glycolysis to the pentose phosphate pathway and production of NADPH for activation of the NADPH oxidase and subsequent respiratory burst. We have developed protocols for the study of human neutrophils by 1H NMR spectroscopy. Importantly, this methodology has sufficient sensitivity and reproducibility to detect changes in metabolite abundance from cell numbers typically collected from clinical samples or experiments with multiple assay conditions.

1H NMR Metabolomics Identifies Underlying Inflammatory Pathology in Osteoarthritis and Rheumatoid Arthritis Synovial Joints.

Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying etiologies are markedly different. We used 1H nuclear magnetic resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100 µL SF was analyzed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analyzed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (false discovery rate (FDR) < 0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by 1H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis.

High dose oral vitamin C and mesenchymal stem cells aid wound healing in a diabetic mouse model.

OBJECTIVE: This study sought to determine the effects of oral vitamin C (VitC) and mesenchymal stem cells (MSCs) on wound healing in diabetic nude mice. METHOD: Bilateral, full-skin thickness wounds were created as an in vivo wound model in BALB/C diabetic nude mice. The mice were separated into five groups: control (CON); diabetes mellitus (DM, from a streptozotocin injection); DM treated with MSCs (DM+MSCs); DM treated with VitC (DM+VitC), and DM treated with MSCs and VitC (DM+MSCs+VitC). After wounding, daily oral-feeding of high dose VitC (1.5g/l) was administered, and a single dose of MSCs (1x106 cells) was given topically using matrix gel application to the wounded area. RESULTS: At day seven, the lowest rate of wound healing, in terms of percentage of wound closure, appeared in the DM group, as compared with the CON and all other treatment groups (mean percentage of wound closure and standard deviation), CON=75.94±7.09%; DM=55.65±9.59%; DM+MSCs=78.57±6.46%; DM+VitC=77.52±3.31%; and DM+MSCs+VitC=84.61±2.87%, p≤0.05. At day 14 post-wounding, the combination of oral high dose VitC and MSCs accelerated wound healing (91.44±3.19%, p≤0.05). In addition, the highest capillary density in DM+MSCs+VitC was obtained at 14 days post-wounding (29.49±7.30%, p≤0.05). CONCLUSION: The findings of this study highlight the possibility of using oral high dose VitC in adjunct to MSCs to increase angiogenesis and accelerate diabetic wound healing in an animal model. This novel therapeutic approach should be studied further to test if it could be a useful adjunct of existing therapies to prevent infection and amputation in patients with diabetes.