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Praveen J Patel,1 Focke Ziemssen,2 Eugene Ng,3 Anushini Muthutantri,4 David Silverman,5 Elizabeth A Tschosik,6 Ronald A Cantrell6 1NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, and University College London Institute of Ophthalmology, London, UK; 2University of Tuebingen, Tuebingen, Germany; 3Institute of Eye Surgery, UPMC Whitfield and Waterford Institute of Technology, Waterford, Ireland; 4IQVIA, London, UK; 5Roche Products Limited, Welwyn Garden City, Hertfordshire, UK; 6Genentech, Inc., A Member of the Roche Group, South San Francisco, CA, USACorrespondence: David SilvermanOphthalmology, Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City AL7 1TW, UKTel +44 1707 36 6394Email david.silverman@roche.comPurpose: To gain comprehensive information on the burden of illness due to geographic atrophy (GA).Methods: This cross-sectional study with a retrospective chart review involved patients aged ≥70 years with physician-confirmed bilateral symptomatic GA due to age-related macular degeneration (GA group), as well as patients of similar age with no ophthalmic condition that in the opinion of the investigator affected visual function (non-GA group). Data relating to patients’ current disease status and sociodemographics were self-reported on patient questionnaires at study entry and extracted from patient charts. Historical data on health care resource utilization (HCRU) were also collected via patient questionnaires and retrospective chart review (GA group only). Overall vision-related functioning and quality of life (QoL) were compared between the GA and non-GA groups using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) composite and subscales, and change in vision over the past year was assessed using the Global Rating of Change Scale.Results: Vision-related functioning and QoL were poorer in patients with vs without GA (n=137 vs 52), as demonstrated by significantly lower NEI-VFQ-25 composite score (mean, 53.1 vs 84.5 points, respectively; P

Praveen J Patel,1 Helen Devonport,2 Sobha Sivaprasad,1 Adam H Ross,3 Gavin Walters,4 Richard P Gale,5 Andrew J Lotery,6 Sajjad Mahmood,7 James S Talks,8 Jackie Napier9 1National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 2The Ophthalmology Department, Bradford Royal Infirmary, Bradford, UK; 3The Ophthalmology Department, Bristol Eye Hospital, Bristol, UK; 4Department of Ophthalmology, Harrogate District Hospital, Harrogate, UK; 5The Ophthalmology Department, The York Hospital and Department of Health Sciences, University of York, York, UK; 6Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 7Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK; 9Medical Affairs, Bayer plc, Reading, Berkshire, UK Abstract: National recommendations on continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration (nAMD) have been developed by an expert panel of UK retina specialists, based on clinician experience and treatment outcomes seen in year 2. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year 1 while attempting to reduce or minimize the treatment burden, recognizing the need for ongoing treatment. At the end of year 1 (ie, the decision visit at month 11), two treatment options should be considered: do not extend the treatment interval and maintain fixed 8-weekly dosing, or extend the treatment interval using a treat-and-extend regimen up to a maximum 12 weeks. Criteria for considering not extending the treatment interval are persistent macular fluid with stable vision, recurrent fluid, decrease in vision in the presence of fluid, macular hemorrhage, new choroidal neovascularization or any other sign(s) of exudative disease activity considered vision threatening in the opinion of the treating clinician. Treatment extension is recommended for eyes with a dry macula (ie, without macular fluid) and stable vision. Under both options, the treatment interval may be shortened if visual and/or anatomic outcomes deteriorate. Monitoring without treatment may be considered for eyes with a fluid-free macula for a minimum duration of 48 weeks. A patient completing one full year of monitoring without requiring injections may be considered for discharge from clinic. The treatment algorithm incorporates return to fixed 8-weekly dosing for disease reactivation during treatment extension and reinstatement of treatment for disease recurrence following discontinuation or discharge. For bilateral nAMD, either the eye requiring the more intensive treatment or the eye with the better vision, guided by local clinical practice, should determine the retreatment schedule overall. Keywords: anti-vascular endothelial growth factor, maintenance therapy, treatment algorithm, treat-and-extend, visual acuity

Daren Hanumunthadu,1 Tomas Ilginis,1 Kamaljit S Balaggan,1,2 Praveen J Patel1 On behalf of the DOCS team 1NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, London, 2Wolverhampton and Midland Counties Eye Infirmary, Wolverhampton, UKChanges in macular thickness measurements in neovascular age-related macular degeneration (nAMD) are thought to reflect disease activity, and can be used to guide treatment with antiangiogenic agents.1 Both spectral-domain optical coherence tomography (SD-OCT) and the more recently introduced swept-source optical coherence tomography (SS-OCT) have onboard segmentation algorithms that deliver automated retinal thickness measurements. Agreement between OCT derived macular thickness measurements is critical for monitoring of patients if these modalities are to be used interchangeably. This prospective cross-sectional study sought to determine the limits of agreement between SD-OCT (Spectralis; Heidelberg Engineering) and SS-OCT (DRI OCT-1 Atlantis; Topcon Medical Systems) in patients with nAMD.

The etiology of aneurysmal bone cysts is uncertain, but they may originate as a localized arteriovenous malformation. These benign lesions can be primary or occur secondary to an underlying lesion. The majority of patients who present with aneurysmal bone cysts are younger than age 20 years. One half of lesions occur within the long bones and one third involve the spine. Most flat bone lesions, approximately 10%, occur in the pelvis. Fluid-fluid levels are common on CT and MRI but are not pathognomonic. Although aneurysmal bone cyst is benign, there may be aggressive clinical and imaging features. Treatment for aneurysmal bone cyst is surgical curettage, intraoperative adjuvant therapy, and bone grafting of the lesion. The prognosis following treatment is very good, although 10% to 20% of cases are reported to recur. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate utility of the newest vital sign (NVS) which can be completed in 3min compared to the short version test of functional literacy in adults (S-TOFHLA) that takes 7min for health literacy in the older African American patients. METHODS: We enrolled 62 older (age>65 years) African American patients and administered the NVS and the S-TOFHLA. A score of less than 4 for the NVS and less than 16 for the S-TOFHLA was indicative of limited health literacy. RESULTS: Mean age of our patients was 73.2+7.9 years with an average education level of twelfth grade. Using S-TOFHLA 51% of the subjects were deemed to be sufficiently literate, with a score of 23.0+8.6 compared to 56% on the NVS with a score of 3.0+1.9. The average time for completing the NVS was 11min in our patient population. CONCLUSION: Based on our data, while health literacy level can be assessed with the NVS its practicality as a quick screening tool in the elderly population appears limited. PRACTICE IMPLICATIONS: Knowing the level of patient's health literacy may help physicians deliver health information in the format that patients can understand. [ABSTRACT FROM AUTHOR]

The management of neovascular age-related macular degeneration (nAMD) has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents). One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication) despite a lack of definitive unbiased safety and efficacy data.~Background~Background~The Avastin(R) (bevacizumab) for choroidal neovascularisation (ABC) trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment). Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining >/= 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change.~Methods and Design~Methods~The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a) defining the control group (b) use of gain in vision as primary efficacy end-point and (c) use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy.~Discussion~Conclusions~Current controlled trials ISRCTN83325075.~Trial Registration~Background [ABSTRACT FROM AUTHOR]

Purpose: To present the results of the Liquid Embolization of Arterial Hemorrhages in Peripheral Vasculature (LAVA) study evaluating safety and efficacy of Lava Liquid Embolic System (Lava LES), an ethylene vinyl alcohol (EVOH), for peripheral arterial hemorrhage (PAH)., Materials and Methods: LAVA was a pivotal, prospective, multicenter, single-group, centrally adjudicated study of adults with active PAH. Patients received EVOH at one of two viscosities, administered by experienced physicians. Primary safety endpoint was freedom from 30-day major adverse events (MAE) defined as ischemia/infarction of target territory, non-target embolization, allergic reaction, and catheter breakage/entrapment. Primary efficacy endpoint was 30-day clinical success defined as absence of bleeding from target lesion after embolization without need for emergency surgery, re-embolization, or other target lesion re-interventions. Secondary endpoints included serious adverse events and mortality., Results: 113 patients (mean age 57.4 years [SD 18.0; range 18.0-93.0]; 63.7% male) with 148 lesions were enrolled at 19 US centers. Targeted areas included non-gastrointestinal (GI) visceral arteries (31.1%), kidneys (26.3%), upper GI (11.5%), lower GI (6.8%) and extremities (6.1%). Empiric embolization was performed for 20.9% of lesions. The primary efficacy endpoint was achieved in 94.3% of lesions (95.3% patients), exceeding the performance goal of 72%. Two target lesions treated with EVOH required subsequent re-embolization. No surgeries were performed for bleeding or ischemia. There were no MAEs reported per study definition. All-cause mortality rate at 30 days was 8.3%., Conclusions: The LAVA study suggests that EVOH is effective and can be safely used as an embolic agent for treatment of PAH., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To evaluate the risk of acute cardiovascular events (CVE), including cardiovascular diseases, cerebrovascular diseases, and all-cause mortality in patients with paracentral acute middle maculopathy (PAMM)., Design: Retrospective cohort study., Methods: We studied 43 individuals with optical coherence tomography-documented PAMM attending Moorfields Eye Hospital between January 2014 and June 2021. We excluded patients with preceding (<2 years) major adverse cardiac events. We stratified patients by age (<50 and ≥50 years) and whether associated with retinal vascular diseases (RVD) or isolated (iPAMM). We assessed risk factors, clinical characteristics, and visual prognosis of the patients. CVE risk was estimated using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression., Results: In young patients with iPAMM patients (n = 12), underlying predisposing factors included six (50%) sickle cell disease and five (41.6%) others, including breakthrough bleeding in pregnancy, migraine, genetic cardiomyopathy, amphetamine use; among those with PAMM + RVD (n = 12) one (9%) had a vascular disorder, and four (44.4%) oral contraceptive use. In the older group of 20 patients, 15 (75%) had at least one coronary risk factor. During a median follow-up of 14 months (range 12-54), older subjects with iPAMM had a higher risk of developing CVE than those with PAMM + RVD (P < .001). Notably, iPAMM displayed a significantly earlier peak in peri-PAMM CVE risk compared to PAMM + RVD (median: one month, range 1-40 months vs 36 months, range 12-54 months). Relative to those with PAMM + RVD, risk of CVE was significantly higher in patients with iPAMM, adjusted for age and sex (hazard ratio: 6.37, 95% confidence interval 1.68-24.14, P = .017). No young patients experienced adverse CVE. At baseline, older iPAMM patients mean best corrected visual acuity of 0.7 (0-1.8) logarithm of the minimum angle resolution, which improved significantly to 0.2 (0-1.30) logarithm of the minimum angle resolution at the latest visit (P = .033)., Conclusions: Young individuals with iPAMM have a higher prevalence of predisposing factors compared to those presenting with combined PAMM + RVD. Older patients with iPAMM had a higher risk of CVE than those with PAMM + RVD, especially in the peri-onset timeframe. This suggests the need for a prompt cardiovascular assessment to rule out systemic etiologies and optimize cardiovascular risk factors, in addition to ongoing ophthalmology input., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Patients with upper extremity deep vein thrombosis (UEDVT) generally present with similar symptoms including arm swelling, erythema, heaviness, or pain. However, this condition is caused by different factors which can influence management decisions. As a result, UEDVT is categorized by primary or secondary etiology. Primary UEDVT is most commonly a result of anatomical subclavian vein compression, whereas secondary UEDVT is most frequently associated with indwelling catheters. Regardless of etiology, anticoagulation therapy is recommended, and interventional treatment is reserved for more severe cases. This series includes outcome data for 8 heterogenous patients treated for UEDVT with mechanical thrombectomy using the ClotTriever System by an interventional radiologist in a single healthcare system. Herein we present procedural imaging for select cases and discuss treatment characteristics and outcomes based on etiology., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objective: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD)., Methods: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated., Results: A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST) are considered, 90% will be eligible for interval extension., Conclusion: Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Acute pancreatitis, a common gastrointestinal ailment in the United States, often lacks a clear etiology, with one-third of cases deemed idiopathic. We discuss an 84-year-old woman with acute pancreatitis possibly linked to a recently introduced weight loss supplement containing apple cider vinegar. Literature review unveils scant data regarding the risks of acute pancreatitis associated with less rigorously studied and regulated supplements, such as apple cider vinegar products. Considering the morbidity and financial burden associated with acute pancreatitis, there is a pressing need to report and disseminate awareness of diverse etiologies, encompassing drug and supplement-induced cases. This case report endeavors to address this need., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Aims: Patients undergoing catheter ablation (CA) of ventricular arrhythmias (VAs) are generally observed overnight in the hospital given the concern for complications. To evaluate the efficacy and safety of same-day discharge (SDD) of patients undergoing elective CA of premature ventricular complexes (PVCs)., Methods and Results: A retrospective evaluation of all patients undergoing elective VA ablation at Ascension St Vincent Hospital from 1 January 2018 to 31 December 2019 was undertaken. Of those, the patients undergoing PVC ablation were divided into SDD and non-SDD. Patients underwent SDD at the discretion of the operator. The primary safety outcome was the 30-day incidence of complications and death. The primary efficacy outcome was procedural success. Among 188 patients who underwent VA ablation, 98 (52.1%) were PVC ablations, and of those, 55 (56.1%) were SDD. There was no difference in age, gender, comorbidities, or ejection fraction between the two groups. Patients that were non-SDD were more likely to be on chronic anticoagulation (P = 0.03), have ablation in the LV (P = 0.04), have retrograde access (P = 0.03), and receive heparin during the procedure (P = 0.01). There were no complications in the SDD group compared with one (2.3%) in the non-SDD group. There was no difference in primary efficacy between the two groups with a 90.9% acute success in the SDD and 88.4% in the non-SDD (P = 0.68)., Conclusion: Same-day discharge for CA of PVCs is feasible and could lower healthcare resource utilization without compromising outcomes in this unique population., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Disclosures The authors have no conflicts of interest to report.

Purpose: To report one-year anatomical and functional real-world outcomes of treatment intensive neovascular age related macular degeneration (nAMD) patients switched to faricimab DESIGN: Retrospective multi-centre cohort study SUBJECTS: Consecutive nAMD patients on 4-weekly treatment interval with either ranibizumab or aflibercept 2mg in the last three visits within a treat and extend protocol (high treatment burden) prior to switch to faricimab at Moorfields Eye Hospital between 5/9/2022- 5/12/2022., Methods: Total number of nAMD patients switched to faricimab were identified from electronic medical records and those who met criteria of high treatment burden were included. Data collected included pre and post-switch visual acuity (VA), treatment intervals, length of follow-up, baseline macular morphology, changes in central subfield thickness (CST), macular fluid status and adverse events., Main Outcome Measures: VA, CST, presence of intraretinal fluid (IRF), subretinal fluid (SRF) and injection intervals over one-year following switch to faricimab., Results: A total of 130/ 286 (45.5%) eyes met inclusion criteria of being switched due to high treatment burden and 117 were included in analysis. Prior to switch to faricimab, these eyes received mean total number of injections of 33.4±19.6 over mean of 51.3±34.9 months. Mean number of injections in 12 months preceding switch was 10.1±1.6 and mean interval of the preceding three injections was 4.2±0.3 weeks. Mean VA, CST and percentage of patients with dry macula prior to switch were 66.0±11.9 ETDRS letters, 259.6±76.0μm and 18.3% respectively. Following switch, there was no statistical difference in mean VA after each visit and at 12 months. Mean CST statistically significantly reduced following the 3 rd faricimab injection and at 12 months by 20.0μm (p=0.035) and 22.1μm (p=0.041) respectively. Mean treatment intervals increased to 6.9±2.3 weeks (p<0.005) at 12 months with 42.9% and 11.4% of patients being on ≥8 weekly and ≥12 weekly treatment intervals respectively., Conclusion: At 12 months, patients with nAMD with previous record of high treatment burden when switched to faricimab maintained visual acuities and improved anatomical outcomes on extended treatment intervals. Physician bias is inherent in these types of observational studies so a prospective randomised controlled trial is recommended to validate these findings., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: The eye is a well-established model of brain structure and function, yet region-specific structural correlations between the retina and the brain remain underexplored. Therefore, we aim to explore and describe the relationships between the retinal layer thicknesses and brain magnetic resonance image (MRI)-derived phenotypes in UK Biobank., Methods: Participants with both quality-controlled optical coherence tomography (OCT) and brain MRI were included in this study. Retinal sublayer thicknesses and total macular thickness were derived from OCT scans. Brain image-derived phenotypes (IDPs) of 153 cortical and subcortical regions were processed from MRI scans. We utilized multivariable linear regression models to examine the association between retinal thickness and brain regional volumes. All analyses were corrected for multiple testing and adjusted for confounders., Results: Data from 6446 participants were included in this study. We identified significant associations between volumetric brain MRI measures of subregions in the occipital lobe (intracalcarine cortex), parietal lobe (postcentral gyrus), cerebellum (lobules VI, VIIb, VIIIa, VIIIb, and IX), and deep brain structures (thalamus, hippocampus, caudate, putamen, pallidum, and accumbens) and the thickness of the innermost retinal sublayers and total macular thickness (all p < 3.3 × 10 -5 ). We did not observe statistically significant associations between brain IDPs and the thickness of the outer retinal sublayers., Conclusions: Thinner inner and total retinal thicknesses are associated with smaller volumes of specific brain regions. Notably, these relationships extend beyond anatomically established retina-brain connections., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy., Methods: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them., Results: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases)., Conclusions: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease., (© 2024. The Author(s).)

Purpose: Application of artificial intelligence (AI) to macular OCT scans to segment and quantify volumetric change in anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD)., Design: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database., Participants: A total of 2115 eyes from 1801 patients starting anti-VEGF treatment between June 1, 2012, and June 30, 2017., Methods: The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes receiving anti-VEGF treatment and had an OCT scan at baseline and 12 months. Follow-up scans were input into the AI system and volumes of OCT variables were studied at different time points and compared with baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test., Main Outcome Measures: Volume outputs of the following variables were studied: intraretinal fluid, subretinal fluid, pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci, neurosensory retina, and retinal pigment epithelium., Results: Mean volumes of analyzed features decreased significantly from baseline to both 4 and 12 months, in both first-treated and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (intraretinal fluid and subretinal fluid) and those with fluid and fibrovascular tissue (PED and SHRM), displayed similar responses to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first 2 months, reaching a plateau postloading phase, and minimal change to 12 months. Both neurosensory retina and retinal pigment epithelium volumes showed gradual reductions over time, and were not as substantial as exudative features., Conclusions: We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pretreatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid the personalization of care. Data will be made public for future studies., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Background: Medicinal plants have curative properties due to the presence of various complex chemical substances of different compositions, which are found as secondary plant metabolites in one or more parts of the plants. Moringa oleifera from Moringaceae and Beta vulgaris root are, native to India, grows in the tropical and subtropical regions of the world. It is commonly known as 'drumstick tree' or 'horseradish tree' or 'miracle tree'. Incorporation of more herbal powder leads to much complexity. Above plants were chosen for their utmost nutritional values., Results: Herbal tablet and granules were prepared and evaluated further for various Physico-chemical parameters as a nutritional supplement. Promising results indicate that prepared formulations have potential as supplements., Conclusions: Present communication mainly focused on estimation of marker components by Reverse Phase-High Performance Liquid Chromatography. It showed the presence of enough number of secondary metabolites and minerals which can be easily consumed by all age groups.

Importance: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials., Objective: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points., Design, Setting, and Participants: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023., Interventions: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month., Main Outcomes and Measures: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal)., Results: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month., Conclusions and Relevance: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors., Trial Registration: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

Introduction: The diagnosis of neovascular age-related macular degeneration (nAMD), the leading cause of visual impairment in the developed world, relies on the interpretation of various imaging tests of the retina. These include invasive angiographic methods, such as Fundus Fluorescein Angiography (FFA) and, on occasion, Indocyanine-Green Angiography (ICGA). Newer, non-invasive imaging modalities, predominately Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), have drastically transformed the diagnostic approach to nAMD. The aim of this study is to undertake a comprehensive diagnostic accuracy assessment of the various imaging modalities used in clinical practice for the diagnosis of nAMD (OCT, OCTA, FFA and, when a variant of nAMD called Polypoidal Choroidal Vasculopathy is suspected, ICGA) both alone and in various combinations., Methods and Analysis: This is a non-inferiority, prospective, randomised diagnostic accuracy study of 1067 participants. Participants are patients with clinical features consistent with nAMD who present to a National Health Service secondary care ophthalmology unit in the UK. Patients will undergo OCT as per standard practice and those with suspicious features of nAMD on OCT will be approached for participation in the study. Patients who agree to take part will also undergo both OCTA and FFA (and ICGA if indicated). Interpretation of the imaging tests will be undertaken by clinicians at recruitment sites. A randomised design was selected to avoid bias from consecutive review of all imaging tests by the same clinician. The primary outcome of the study will be the difference in sensitivity and specificity between OCT+OCTA and OCT+FFA (±ICGA) for nAMD detection as interpreted by clinicians at recruitment sites., Ethics and Dissemination: The study has been approved by the South Central-Oxford B Research Ethics Committee with reference number 21/SC/0412.Dissemination of study results will involve peer-review publications, presentations at major national and international scientific conferences., Trial Registration Number: ISRCTN18313457., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD., Methods: We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex., Discussion: Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life., Trial Registration: The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024., (© 2024. The Author(s).)

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains. Additionally, the majority of the synthesized compounds demonstrated remarkable antifungal activity, against Candida albicans and Aspergillus niger, as compared to nystatin, griseofulvin, and fluconazole. Furthermore, the majority of compounds exhibited notable inhibitory effects against the Plasmodium falciparum strain, having IC 50 values ranging from 1.31 to 2.79 μM as compared to standard quinine (2.71 μM). Cytotoxicity evaluation of compounds 5a-q on SHSY-5Y cells at up to 100 μg/mL showed no adverse effects. Comparison with control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding to target active sites, with stable protein-ligand complexes displaying drug-like molecules. Molecular dynamics simulations revealed dynamic stability and interactions. Rigorous tests and molecular modeling unveil the effectiveness of the compounds against drug-resistant microbes, providing hope for new antimicrobial compounds with potential safety., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Introduction: There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR)., Methods: We conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10 mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5 mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas., Results: On clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10 mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group., Conclusions: Our study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization., (© 2024. The Author(s).)

Purpose: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease., Design: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank., Participants: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging., Methods: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery., Main Outcome Measures: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses., Results: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P < 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P < 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% confidence interval [CI], -0.97 to -0.12; P  = 0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI, -0.12 to 0.13; P  = 0.97). The association between PRL thickness and very severe periodontitis was modified by age ( P < 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 μm, 95% CI, -1.85 to -0.53; P < 0.001) but not among those aged < 60 years., Conclusions: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Atrial fibrillation (AF) and heart failure (HF) synergistically interact to exacerbate each other. However, treatment of one entity can greatly improve management of the other. Although historically, permissive medical therapy was the mainstay of AF management in the HF population, recent data strongly favor early, often invasive, intervention for AF to reduce hard HF outcomes. It seems that intervening earlier in the time course of AF, though still not excluding persistent AF from treatment, may have more pronounced effects., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD)., Methods: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years)., Results: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes., Discussion: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: To evaluate the effect pegcetacoplan, a C3 and C3b inhibitor, on the rate of progression of geographic atrophy (GA) as assessed by spectral domain optical coherence tomography (SD-OCT) using a split-person study design and deep-learning quantification., Methods: A post hoc analysis of phase 2 FILLY trial data comparing study (treated monthly, treated every other month and sham-treated) and fellow (untreated) eyes in a split-person study design was performed. This analysis included 288 eyes from 144 patients with bilateral GA from the FILLY phase 2 trial (Clinical Trials identifier: NCT02503332). Only patients with bilateral GA and without evidence of choroidal neovascularisation in either eye were included. Patient study eyes were treated with sham injections or with pegcetacoplan monthly (PM) or every other month (PEOM) for 12 months. SD-OCT scans of study and fellow eyes taken at baseline and 12 months were used for the analysis. The main outcomes were the annual change in the area of retinal pigment epithelial and outer retinal atrophy (RORA), its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, hypertransmission) and intact macula as compared to the untreated fellow eye., Results: Annual GA growth was reduced in eyes treated with PM versus untreated fellow eyes for OCT features, including RORA (study eye 0.792 vs. fellow eye 1.13 mm 2 ; P = 0.003), PRD (0.739 vs. 1.23 mm 2 ; P = 0.015), RPE-loss (0.789 vs. 1.17 mm 2 ; P = 0.007) and intact macula (- 0.735 vs. - 1.29 mm 2 ; P = 0.011). Similar (but not statistically significant) trends were observed with the PEOM treatment or when GA was quantified with fundus autofluorescence (FAF). The sham treatment demonstrated no effect. Pearson correlation coefficients showed concordance in the enlargement rate of GA between the study and fellow eyes in the sham (R = 0.64) and PEOM (R = 0.68) groups, but not in the PM group (R = 0.21)., Conclusions: Pegcetacoplan-treated eyes demonstrated a reduction in spatial GA progression compared to their untreated counterparts. This effect was more evident on OCT than with FAF., Trial Registration: Clinical Trials identifier: NCT02503332., (© 2023. The Author(s).)

An intramolecular iron-catalyzed nitroso ene reaction was developed to afford six- or seven-membered N -heterocycles from nitroarenes using an earth abundant iron catalyst and phenylsilane as the terminal reductant. The reaction can be triggered using as little as 3 mol % of iron(II) acetate and 3 mol % of 4,7-dimethoxyphenanthroline as the ligand. The scope of the reaction is broad tolerating a range of electron-releasing or electron-withdrawing substituents on the nitroarene, and the ortho -substituent can be modified to diastereoselectively construct benzoxazines, dihydrobenzothiazines, tetrahydroquinolines, tetrahydroquinoxalines, or tetrahydrobenzooxazepines. Mechanistic investigations indicated that the reaction proceeds via a nitrosoarene intermediate, and kinetic analysis of the reaction revealed a first-order rate dependence in catalyst-, nitroarene-, and silane concentration, and an inverse kinetic order in acetate was observed. The difference in rates between PhSiH 3 and PhSiD 3 was found to be 1.50 ± 0.09, and investigation of the temperature dependence of the reaction rate revealed that the activation parameters to be ΔH ‡ = 13.5 kcal•mol -1 and ΔS ‡ = -39.1 cal•mol -1 •K -1 . These data were interpreted to indicate that the turnover-limiting step to be hydride transfer from iron to the coordinated nitroarene, which occurs through an ordered transition state with little Fe-H bond breaking.