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Valencia Hui Xian Foo,1 Tiffany Sin Hui Bong,1 Andrew Tsai,1,2 Laurence Shen Lim,1,2 Shamira Asith Perera1,2 1Department of Ophthalmology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; 2Eye-Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, SingaporeCorrespondence: Shamira Asith PereraSingapore National Eye Centre, 11 Third Hospital Avenue, 168751, SingaporeTel +65 6227 7255Fax +65 62263 995Email shamira.perera@singhealth.com.sgImportance/Background: To describe the characteristics and 1-year postoperative surgical outcomes of primary combined trans pars plana vitrectomy (TPPV) with iris-fixated posterior-chamber intraocular lens (IF-PCIOL) implantation for subluxated cataracts and intraocular lenses (IOLs).Methods: Consecutive cases of significantly subluxated cataracts and IOLs from January 2014 to May 2019 were included in this retrospective case series.Results: A total of 103 eyes of 103 patients were included. Median age was 67.4 (interquartile range [IQR] 27– 89) years. Thirty-two (31.1%) had subluxated cataracts, while 71 (68.9%) had subluxated IOLs. Overall median preoperative logMAR BCVA was 0.9 (IQR 0– 2.5). Median logMAR BCVA improved to 0.3 (0– 1.9) and 0.2 (0– 1.8) for the subluxated cataract and IOL groups, 81.2% and 75% of eyes achieved logMAR ≤ 0.3, and 94% and 97% achieved IOL stability at month 12, respectively. Eyes with subluxated IOLs had a significantly less myopic median SE if a new IOL was implanted compared to iris-fixating the dislocated IOL.Conclusion: Combined primary TPPV and IF-PCIOL implantation is a good surgical option for subluxated IOL or cataract without sufficient capsular support, with at least 75% achieving logMAR BCVA ≤ 0.3 and 95% IOL stability at postoperative year 1. In eyes with subluxated IOLs, explanting that IOL and iris-fixating a new IOL led to a reduced SE and better visual outcome at postoperative month 12 when compared to iris-fixating the dislocated IOL.Keywords: subluxated cataracts, subluxated intraocular lenses, secondary intraocular lens fixation, iris-fixation, trans pars plana vitrectomy

Anaphylactic shock is characterized by elevated immunoglobulin-E (IgE) antibodies that signal via the high affinity Fcε receptor (FcεRI) to release inflammatory mediators. Here we report that the novel cytokine interleukin-33 (IL-33) potently induces anaphylactic shock in mice and is associated with the symptom in humans. IL-33 is a new member of the IL-1 family and the ligand for the orphan receptor ST2. In humans, the levels of IL-33 are substantially elevated in the blood of atopic patients during anaphylactic shock, and in inflamed skin tissue of atopic dermatitis patients. In murine experimental atopic models, IL-33 induced antigen-independent passive cutaneous and systemic anaphylaxis, in a T cell-independent, mast cell-dependent manner. In vitro, IL-33 directly induced degranulation, strong eicosanoid and cytokine production in IgE-sensitized mast cells. The molecular mechanisms triggering these responses include the activation of phospholipase D1 and sphingosine kinasel to mediate calcium mobilization, Nuclear factor-κB activation, cytokine and eicosanoid secretion, and degranulation. This report therefore reveals a hither to unrecognized pathophysiological role of IL-33 and suggests that IL-33 may be a potential therapeutic target for anaphylaxis, a disease of considerable unmet medical need. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are primary sensors of both innate and adaptive immune systems and play a pivotal role in response against structurally conserved components of pathogens. Synthetic bacterial lipoprotein (BLP) Pam3Cys-SK4 is a TLR2 agonist that is capable of modulating T cell immune responses. We show here that BLP, together with anti-CD3 antibody [T cell receptor (TcR) activation], induced proliferation of both CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25- (effector) T cells in the absence of antigen-presenting cells. The expanded Tregs showed a transient loss of suppressive activity. Moreover, BLP rendered effectors resistant to the suppression of Tregs by increasing IL-2 secretion. BLP also transiently suppressed the induction of Foxp3 (X-linked forkhead/winged helix transcription factor) mRNA in Tregs at the first 8–15 h after T cell receptor activation. Consistent with this observation, BLP-stimulated Tregs regained their inhibitory activity and prevented spontaneous colitis induced by effectors in severe combined immunodeficient mice. Our results demonstrate a previously unrecognized pathway by which TLR expressed on T cells may directly modulate the immune response. Thus, during an acute bacterial infection, BLP may rapidly increase the host's adaptive immunity by expanding effectors and also by attenuating the suppressive activity of Tregs. In the process, BLP also expands the Tregs, which recover their suppressive activity when the infection has subsided, in time to limit potential autoimmunity that might result from the overactivated effectors. [ABSTRACT FROM AUTHOR]

Valencia Hui Xian Foo,1 Sarah En Mei Tan,2 David Ziyou Chen,3 Shamira A Perera,1,4 Charumathi Sabayanagam,4,5 Eva Katie Fenwick,4,5 Tina T Wong,1,4,5 Ecosse L Lamoureux4–6 1Singapore National Eye Centre, Singapore; 2Tan Tock Seng Hospital, Singapore; 3Department of Ophthalmology, National University of Singapore and National University Health System, Singapore; 4Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; 5Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 6Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia Objective: The aim of this study was to evaluate patients’ dissatisfaction with overall and specific aspects of a tertiary glaucoma service and to determine their independent factors, including intraocular pressure (IOP) and visual acuity (VA). Methods: Patients, aged ≥21 years, from a specialist glaucoma service in a tertiary eye hospital in Singapore for at least 6 months, were recruited for this cross-sectional study between March and June 2014. All consenting patients completed a 7-area glaucoma-specific satisfaction questionnaire and one item related to satisfaction with overall glaucoma care. We determined the top three areas of dissatisfaction and overall dissatisfaction with the glaucoma service. We also explored the independent factors associated with overall and specific areas of patients’ dissatisfaction with their glaucoma care, including VA and IOP by using logistic regression models. Results: Of the 518 patients recruited, 438 (84.6%) patients completed the study. Patients’ dissatisfaction with the overall glaucoma service was 7.5%. The three areas of glaucoma service with the highest dissatisfaction rates were as follows: 1) explanation of test results (24.8%); 2) explanation of glaucoma complications (23.7%); and 3) advice on managing glaucoma (23.5%). Patients who were dissatisfied with the overall service had a worse mean VA compared with satisfied patients (logarithm of the minimum angle of resolution =0.41±0.43 vs 0.27±0.49, p=0.005), whereas mean IOP remained well-controlled in both the groups (13.55±2.46 mmHg vs 14.82±2.86 mmHg, p=0.014). In adjusted models, factors associated with overall dissatisfaction with glaucoma care included a pre-university education and above (odds ratio [OR] =8.06, 95% CI =1.57–41.27) and lower IOP (OR =0.83, 95% CI =0.71–0.98). Conclusion: Although less than one tenth of glaucoma patients were dissatisfied with the overall glaucoma service, one in four patients were dissatisfied with three specific aspects of care. A lower IOP, ironically, and education level were associated with overall dissatisfaction. Improving patients’ understanding of glaucoma test results, glaucoma complications, and disease management may increase patient satisfaction levels. Keywords: physician-patient relations, perception, attitude to health, surveys and questionnaires, quality of health care

Rationale and Key Points: This article explains how to implement compassionate leadership in nursing teams. Compassionate leadership is an approach that aims to empower and support staff through four main behavioural principles - attending, understanding, empathising and helping. • Compassionate leadership can be practised by all nurses, irrespective of their role or position, and with individuals or groups. • For the nurse, understanding and reflecting on their own leadership style is the starting point for compassionate leadership, after which nurses may consider leading others. • Implementing compassionate leadership can empower teams, enhancing team members' performance, motivation and well-being. • Compassionate leadership can also support improved outcomes for patients, since motivated nurses are more likely to provide high-quality care. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: • How this article might help you to introduce compassionate leadership into your nursing team. • How you could use this article to educate nursing colleagues and students about the role of compassionate leadership in nursing teams., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

The cornea is the major contributor to the refractive power of the eye, and corneal diseases are a leading cause of reversible blindness. The main treatment for advanced corneal disease is keratoplasty: allograft transplantation of the cornea. Examples include lenticule implantation to treat corneal disorders (e.g. keratoconus) or correct refractive errors. These procedures are limited by the shelf-life of the corneal tissue, which must be discarded within 2-4 weeks. Electron-beam irradiation is an emerging sterilisation technique, which extends this shelf life to 2 years. Here, we produced lenticules from fresh and electron-beam (E-beam) irradiated corneas to establish a new source of tissue for lenticule implantation. In vitro, in vivo, and ex vivo experiments were conducted to compare fresh and E-beam-irradiated lenticules. Results were similar in terms of cutting accuracy, ultrastructure, optical transparency, ease of extraction and transplantation, resilience to mechanical handling, biocompatibility, and post-transplant wound healing process. Two main differences were noted. First, ∼59% reduction of glycosaminoglycans resulted in greater compression of E-beam-irradiated lenticules post-transplant, likely due to reduced corneal hydration-this appeared to affect keratometry after implantation. Cutting a thicker lenticule would be required to ameliorate the difference in refraction. Second, E-beam-sterilised lenticules exhibited lower Young's modulus which may indicate greater care with handling, although no damage or perforation was caused in our procedures. In summary, E-beam-irradiated corneas are a viable source of tissue for stromal lenticules, and may facilitate on-demand lenticule implantation to treat a wide range of corneal diseases. Our study suggested that its applications in human patients are warranted. STATEMENT OF SIGNIFICANCE: Corneal blindness affects over six million patients worldwide. For patients requiring corneal transplantation, current cadaver-based procedures are limited by the short shelf-life of donor tissue. Electron-beam (E-beam) sterilisation extends this shelf-life from weeks to years but there are few published studies of its use. We demonstrated that E-beam-irradiated corneas are a viable source of lenticules for implantation. We conducted in vitro, in vivo, and ex vivo comparisons of E-beam and fresh corneal lenticules. The only differences exhibited by E-beam-treated lenticules were reduced expression of glycosaminoglycans, resulting in greater tissue compression and lower refraction suggesting that a thicker cut is required to achieve the same optical and refractive outcome; and lower Young's modulus indicating extra care with handling., Competing Interests: Declaration of Competing Interest ACK and JS work for Lions World Vision Institute which produces E-beam-irradiated corneas as a commercial product (OptiGraft®). All other authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Age-related macular degeneration (AMD) is one of the leading causes of vision impairment globally and early detection is crucial to prevent vision loss. However, the screening of AMD is resource dependent and demands experienced healthcare providers. Recently, deep learning (DL) systems have shown the potential for effective detection of various eye diseases from retinal fundus images, but the development of such robust systems requires a large amount of datasets, which could be limited by prevalence of the disease and privacy of patient. As in the case of AMD, the advanced phenotype is often scarce for conducting DL analysis, which may be tackled via generating synthetic images using Generative Adversarial Networks (GANs). This study aims to develop GAN-synthesized fundus photos with AMD lesions, and to assess the realness of these images with an objective scale., Methods: To build our GAN models, a total of 125,012 fundus photos were used from a real-world non-AMD phenotypical dataset. StyleGAN2 and human-in-the-loop (HITL) method were then applied to synthesize fundus images with AMD features. To objectively assess the quality of the synthesized images, we proposed a novel realness scale based on the frequency of the broken vessels observed in the fundus photos. Four residents conducted two rounds of gradings on 300 images to distinguish real from synthetic images, based on their subjective impression and the objective scale respectively., Results and Discussion: The introduction of HITL training increased the percentage of synthetic images with AMD lesions, despite the limited number of AMD images in the initial training dataset. Qualitatively, the synthesized images have been proven to be robust in that our residents had limited ability to distinguish real from synthetic ones, as evidenced by an overall accuracy of 0.66 (95% CI: 0.61-0.66) and Cohen's kappa of 0.320. For the non-referable AMD classes (no or early AMD), the accuracy was only 0.51. With the objective scale, the overall accuracy improved to 0.72. In conclusion, GAN models built with HITL training are capable of producing realistic-looking fundus images that could fool human experts, while our objective realness scale based on broken vessels can help identifying the synthetic fundus photos., Competing Interests: DT and TW are co-inventors, with patents pending, for a deep learning system for diabetic retinopathy, glaucoma, and age-related macular degeneration (SG Non-Provisional Application number 10201706186V), and a computer-implemented method for training an image classifier using weakly annotated training data (SG Provisional Patent Application number 10201901083Y), and are co-founders and shareholders of EyRIS, Singapore. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Lim, Ng, Tan, Lim, Lim, Foo, Lim, Sinisterra, Zheng, Liu, Tan, Cheng, Cheung, Wong and Ting.)

Purpose: To study the role of two anterior segment optical coherence tomography angiography (AS-OCTA) systems in eyes with acute chemical injury., Methods: Prospective study in subjects with unilateral chemical injuries. Sequential slit-lamp assessment with spectral domain (SD) (AngioVue, Optovue, USA) and swept source (SS) (Plex Elite, Zeiss, Carl Zeiss Meditec, Dublin, California, USA) AS-OCTA was performed in both eyes within 24-48 hours of injury. Subjects were managed with a standard clinical protocol and followed-up for 3 months. We assessed limbal disruption (loss of normal limbal vessel architecture), limbal vessel density measurements and agreement (kappa coefficient, κ) between masked assessors of limbal disruption based on AS-OCTA scans and slit-lamp assessment., Results: Ten subjects with median age 31 (25-33) years, 20% women, 60% suffered alkali injuries (Roper-Hall grade 1.5±0.7, Dua grade 2.3±1.2) at presentation. Mean limbal vessel density was lower in quadrants of affected eyes compared with controls detected by SD AS-OCTA (9.4%±2.0% vs 15.5%±1.8%, p<0.001) and SS AS-OCTA (8.8%±2.5% vs 13.9%±1.3%, p=0.01). There was substantial agreement when assessing limbal disruption on AS-OCTA (κ=0.7) compared with slit-lamp evaluation (κ=0.4). Overall, we found good agreement between SD and SS AS-OCTA systems in assessing limbal vessel density in eyes with chemical injury at presentation (mean paired difference: -1.08, 95% CI -3.2 to 0.5; p=0.189)., Conclusions: In this pilot study, AS-OCTA provided objective, non-contact, rapid assessment of limbal vasculature involvement in eyes with acute chemical injury. Further studies are required to establish the role of AS-OCTA in determining the prognosis of eyes with chemical injury., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

To examine the use of anterior segment-optical coherence tomography angiography (AS-OCTA) in the assessment of limbal ischemia in an animal model chemical ocular injury. We conducted a prospective study using an established chemical ocular injury model in 6 rabbits (12 eyes), dividing the cornea limbus into 4 quadrants. Chemical injury grade was induced based on extent of limbal injury (0 to 360 degrees) and all eyes underwent serial slit-lamp with AS-OCTA imaging up to one month. Main outcome measure was changes in AS-OCTA vessel density (VD) comparing injured and control cornea limbal quadrants within 24 h and at one month. AS-OCTA was able to detect differences in limbal VD reduction comparing injured (3.3 ± 2.4%) and control quadrants (7.6 ± 2.3%; p < 0.001) within 24 h of ocular chemical injury. We also observed that AS-OCTA VD reduction was highly correlated with the number of quadrants injured (r = - 0.89; p < 0.001; 95% CI - 5.65 to - 1.87). Corneal vascularization was detected by AS-OCTA in injured compared to control quadrants (10.1 ± 4.3% vs 7.0 ± 1.2%; p = 0.025) at 1 month. Our animal pilot study suggests that AS-OCTA was able to detect limbal vessel disruption from various severities of acute chemical insult, and in the future, could potentially serve as an adjunct in providing objective grading of acute ocular chemical injury once validated in a clinical trial., (© 2021. The Author(s).)

Background: The aim of the present study was to examine the association between variability in HbA1c or systolic blood pressure (SBP) and diabetes-specific moderate retinopathy in Asians with type 2 diabetes (T2D)., Methods: A retrospective study was conducted of 172 cases of moderate diabetic retinopathy (DR) cases and 226 controls without DR, matched for age, sex, and ethnicity. Serial HbA1c and SBP (range 3-6 readings) over the 2 years prior to photographic screening of DR were collected. Intrapersonal mean and SD values for HbA1c (iM-HbA1c and iSD-HbA1c) and SBP (iM-SBP and iSD-SBP) were derived. Moderate DR was assessed from digital retinal photographs and defined as levels >43 using the Early Treatment Diabetic Retinopathy Study scale., Results: Cases of moderate DR had higher iM-HbA1c (8.2 % vs 7.3 %; P = 0.001), iSD-HbA1c (1.22 vs 0.64; P = 0.001), iM-SBP (136.8 vs 129.6 mmHg; P = 0.001) and iSD-SBP (13.3 vs 11.1; P = 0.002) than controls. In the multivariate regression model adjusted for age, gender, ethnicity, duration of diabetes, SBP, and HbA1c, iM-HbA1c and iM-SBP were significantly associated with moderate DR (odds ratio [OR] 1.80, 95 % confidence interval [CI] 1.37-2.36; and OR 1.03, 95 % CI 1.01-1.05, respectively). Neither iSD-HbA1c nor iSD-SBP were associated with moderate DR. When stratified by HbA1c <7 %, only iSD-SBP remained significantly associated with moderate DR (OR 1.11, 95 % CI 1.01-1.21)., Conclusion: In a cohort of Asian patients with T2D, both higher mean HbA1c levels and SBP, but not their variability, were associated with moderate DR. Among those with good glycemic control, wider variability of SBP is associated with moderate DR., (© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Descemet stripping automated endothelial keratoplasty (DSAEK) is the most common corneal transplant procedure. A key step in the procedure is preparing the donor cornea for transplantation. This can be accomplished via 1 of 3 alternatives: surgeon cuts the cornea on the day of surgery, the cornea is precut ahead of time in an offsite facility by a trained technician, or a precut cornea is purchased from an eye bank. Currently, there is little evidence on the costs and effectiveness of these 3 strategies to allow healthcare providers decide upon the preferred method to prepare grafts.The aim of this study was to compare the costs and relative effectiveness of each strategy.The Singapore National Eye Centre and Singapore Eye Bank performed both precut cornea and surgeon-cut cornea transplant services between 2009 and 2013.This study included 110 subjects who received precut cornea and 140 who received surgeon-cut cornea. Clinical outcomes and surgical duration were compared across the strategies using the propensity score matching. The cost of each strategy was estimated using the microcosting and consisted of facility costs and procedural costs including surgical duration. One-way sensitivity analysis and threshold analysis were performed.The cost for DSAEK was highest for the surgeon-cut approach ($13,965 per procedure), followed by purchasing precut corneas ($12,659) and then setting up precutting ($12,421). The higher procedural cost of the surgeon-cut approach was largely due to the longer duration of the procedure (surgeon-cut = 72.54 minutes, precut = 59.45 minutes, P < 0.001) and the higher surgeon fees. There was no evidence of differences in clinical outcomes between grafts that were precut or surgeon-cut. Threshold analysis demonstrated that if the number of cases was below 31 a year, the strategy that yielded the lowest cost was purchasing precut cornea from eye bank. If there were more than 290 cases annually, the cheapest option would be to setup precutting facility.Our findings suggest that it is more efficient for centers that are performing a large number of cornea transplants (more than 290 cases) to set up their own facility to conduct precutting.

Pressure ulcers are common problems for bedridden patients. Caregivers need to reposition the sleeping posture of a patient every two hours in order to reduce the risk of getting ulcers. This study presents the use of Kurtosis and skewness estimation, principal component analysis (PCA) and support vector machines (SVMs) for sleeping posture classification using cost-effective pressure sensitive mattress that can help caregivers to make correct sleeping posture changes for the prevention of pressure ulcers.