Search

The World Health Organization (WHO) has recently released a new child growth standard that it recommends for international use. The objective of this study was to demonstrate the differences and the implications of using the WHO child growth standards on Saudi children. The Saudi reference was based on a cross-sectional sample of the population of healthy children and adolescents from birth to 19 years of age. The WHO sample was selected from privileged households in some countries. Percentile construction and smoothing were performed using the lambda, mu, sigma (LMS) methodology in both studies. The data from the WHO study including the 3rd, 5th, 50th, 95th, and 97th percentiles were plotted on the Saudi charts for weight for age, height for age, and weight for height. There are major differences between the 2 studies. Compared with the Saudi charts, the WHO lower percentiles (third and fifth) are shifted upward, whereas the upper percentiles are shifted downward. The use of the WHO standards in Saudi Arabia and possibly in other countries of similar socioeconomic status increases the prevalence of undernutrition, stunting, and wasting, potentially leading to unnecessary referrals, investigations, and parental anxiety. Clear guidelines should be developed by WHO experts to guide clinicians in developing countries in the proper use of the standards not only to determine prevalence but also in the daily clinical assessment of the growth of children [ABSTRACT FROM AUTHOR]

Background: There is limited data regarding the morbidity and progression to primary angle closure glaucoma in those presenting with acute primary angle closure (APAC) in the UK. We aim to report on the vision and intraocular pressure (IOP) outcomes and treatment required after an APAC episode and to identify any risk factors that could predict worse outcomes., Methods: A retrospective observational case series review including 117 consecutive patients (121 eyes) attending Moorfields Eye Hospital, at a tertiary referral unit in the UK, with APAC was performed., Results: Most patients (73%) had visual acuities of ≥6/12, meeting the UK driving standard, at the final follow-up. Only 15% (17 eyes) had severe visual impairment, as defined by the WHO, in the affected eye, of which 6.6% (eight eyes) were due to glaucoma. The delayed presentation was linked to a higher need for further medical treatment (OR=2.83, 95% CI 1.09 to 7.40, p=0.03). Patients who underwent phacoemulsification were at lower risk of having blindness in the affected eye (OR 0.18, 95% CI 0.05 to 0.69, p=0.01), having elevated IOP (OR 0.10, 95% CI 0.01 to 0.75, p=0.02) or requiring further medical treatment (OR 0.34, 95% CI 0.12 to 0.99, p=0.04). Older age (OR 1.26, 95% CI 1.08 to 1.48, p<0.01) was associated with worse visual outcomes., Conclusions: APAC causes low long-term visual and treatment morbidity in this largely Caucasian patient group in the UK. Phacoemulsification as a treatment may enhance visual outcomes and reduce the need for further IOP-lowering treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sentinel lymph node biopsy (SLNB) is an important cancer diagnostic staging procedure. Conventional SLNB procedures with 99m Tc radiotracers and scintigraphy are constrained by tracer half-life and, in some cases, insufficient image resolution. Here, we explore an alternative magnetic (nonradioactive) image-guided SLNB procedure., Purpose: To demonstrate that magnetic particle imaging (MPI) lymphography can sensitively, specifically, and quantitatively identify and map sentinel lymph modes (SLNs) in murine models in multiple regional lymphatic basins., Materials and Methods: Iron oxide nanoparticles were administered intradermally to healthy C57BL/6 mice (male, 12-week-old, n = 5). The nanoparticles (0.675 mg Fe/kg) were injected into the tongue, forepaw, base of tail, or hind footpad, then detected by 3-dimensional MPI at multiple timepoints between 1 hour and 4 to 6 days. In this mouse model, the SLN is represented by the first lymph node draining from the injection site. SLNs were extracted to verify the MPI signal ex vivo and processed using Perl's Prussian iron staining. Paired t -test was conducted to compare MPI signal from SLNs in vivo vs. ex vivo and considered significant if P  < .05., Results: MPI lymphography identified SLNs in multiple lymphatic pathways, including the cervical SLN draining the tongue, axillary SLN draining the forepaw, inguinal SLN draining the tail, and popliteal SLN draining the footpad. MPI signal in lymph nodes was present after 1 hour and stable for the duration of the study (4-6 days). Perl's Prussian iron staining was identified in the subcapsular space of excised SLNs., Conclusion: Our data support the use of MPI lymphography to specifically detect SLN(s) using a magnetic tracer for a minimum of 4 to 6 days, thereby providing information required to plan the SLN approach in cancer surgery. As clinical-scale MPI is developed, translation will benefit from a history of using iron-oxide nanoparticles in human imaging and recent regulatory-approvals for use in SLNB., Competing Interests: Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials. Authors O.C. Sehl., K. Guo, A.R. Mohtasebzadeh, P. Kim, B. Fellows, M. Weyhmiller, P.W. Goodwill, and J.M. Greve are employees of Magnetic Insight Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Radiological Society of North America.)

Purpose: Glaucoma is the leading cause of irreversible blindness worldwide. Despite growing concerns about air quality and its impact on ocular health, there remains a knowledge gap regarding the long-term association between air pollution and glaucoma risk. This study investigates the relationship between exposure to ambient air pollution and incidence of glaucoma., Methods: In this prospective study, we used land use regression models to estimate levels of various air pollutants, including fine particulate matter (PM2.5), PM2.5 absorbance, PM2.5-10, PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). Incidents of glaucoma were ascertained through routinely collected hospital admission records. Multivariate Cox proportional hazards models were used to examine the associations between air pollution exposure and glaucoma incidence, adjusting for potential confounding sociodemographic, physical, and lifestyle factors., Results: Data from 481,113 participants were included. Over a median follow-up of 12.8 years, 9224 incident cases of glaucoma were identified. In the maximally adjusted model, per interquartile range increase in PM2.5 was associated with a 3% greater risk of developing glaucoma (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.048). Participants in the highest quartile had a 10% increased risk of developing glaucoma compared to those in the lowest quartile (HR = 1.10, 95% CI = 1.03 to 1.17, P = 0.005)., Conclusions: Higher levels of exposure to ambient air pollutants, particularly PM2.5, are associated with an increased risk of developing glaucoma. These results highlight the potential public health impact of ambient air pollution on glaucoma risk and underscore the urgent need for further research into targeted environmental interventions in this domain.

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H 2 S) production on bladder cell viability and in vivo tumor progression. We targeted the H 2 S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H 2 S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro ( p < 0.0001) and tumor growth ( p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression ( p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis ( p < 0.05), as well as intratumoral CD8 + T cell ( p < 0.05) and F4/80 + macrophage ( p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization ( p < 0.0001) and cell proliferation ( p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H 2 S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

Purpose: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease., Design: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study., Participants: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data., Methods: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions., Main Outcome Measures: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma., Results: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score., Conclusions: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: The emerging concept of retinal age, a biomarker derived from retinal images, holds promise in estimating biological age. The retinal age gap (RAG) represents the difference between retinal age and chronological age, which serves as an indicator of deviations from normal ageing. This scoping review aims to collate studies on retinal age to determine its potential clinical utility and to identify knowledge gaps for future research., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, eligible non-review, human studies were identified, selected and appraised. PubMed, Scopus, SciELO, PsycINFO, Google Scholar, Cochrane, CINAHL, Africa Wide EBSCO, MedRxiv and BioRxiv databases were searched to identify literature pertaining to retinal age, the RAG and their associations. No restrictions were imposed on publication date., Results: Thirteen articles published between 2022 and 2023 were analysed, revealing four models capable of determining biological age from retinal images. Three models, 'Retinal Age', 'EyeAge' and a 'convolutional network-based model', achieved comparable mean absolute errors: 3.55, 3.30 and 3.97, respectively. A fourth model, 'RetiAGE', predicting the probability of being older than 65 years, also demonstrated strong predictive ability with respect to clinical outcomes. In the models identified, a higher predicted RAG demonstrated an association with negative occurrences, notably mortality and cardiovascular health outcomes., Conclusion: This review highlights the potential clinical application of retinal age and RAG, emphasising the need for further research to establish their generalisability for clinical use, particularly in neuropsychiatry. The identified models showcase promising accuracy in estimating biological age, suggesting its viability for evaluating health status., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prcis: While glaucoma is a leading cause of irreversible vision loss, it presents technical challenges in the design and implementation of screening. New technologies such as PRS and AI offer potential improvements in our ability to identify people at high risk of sight loss from glaucoma and may improve the viability of screening for this important disease., Purpose: To review the current evidence and concepts around screening for glaucoma., Methods/results: A group of glaucoma-focused clinician scientists drew on knowledge and experience around glaucoma, its etiology, and the options for screening. Glaucoma is a chronic progressive optic neuropathy affecting around 76 million individuals worldwide and is the leading cause of irreversible blindness globally. Early stages of the disease are asymptomatic meaning a substantial proportion of cases remain undiagnosed. Early detection and timely intervention reduce the risk of glaucoma-related visual morbidity. However, imperfect tests and a relatively low prevalence currently limit the viability of population-based screening approaches. The diagnostic yield of opportunistic screening strategies, relying on the identification of disease during unrelated health care encounters, such as cataract clinics and diabetic retinopathy screening programs, focusing on older people and/or those with a family history, are hindered by a large number of false-positive and false-negative results. Polygenic risk scores (PRS) offer personalized risk assessment for adult-onset glaucoma. In addition, artificial intelligence (AI) algorithms have shown impressive performance, comparable to expert humans, in discriminating between potentially glaucomatous and non-glaucomatous eyes. These emerging technologies may offer a meaningful improvement in diagnostic yield in glaucoma screening., Conclusions: While glaucoma is a leading cause of irreversible vision loss, it presents technical challenges in the design and implementation of screening. New technologies such as PRS and AI offer potential improvements in our ability to identify people at high risk of sight loss from glaucoma and may improve the viability of screening for this important disease., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Importance: Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS., Objective: To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC)., Design, Setting, and Participants: This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up., Results: The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 μm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 μm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 μm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance., Conclusions and Relevance: This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 μm and light-room ARA at 750 μm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.

Aims: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects., Methods: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression., Results: A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement)., Conclusion: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease., Trial Registration Number: ISRCTN45213099., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Microtubules and molecular motors are essential components of the cellular cytoskeleton, driving fundamental processes in vivo, including chromosome segregation and cargo transport. When reconstituted in vitro, these cytoskeletal proteins serve as energy-consuming building blocks to study the self-organization of active matter. Cytoskeletal active gels display rich emergent dynamics, including extensile flows, locally contractile asters, and bulk contraction. However, it is unclear how the protein-protein interaction kinetics set their contractile or extensile nature. Here, we explore the origin of the transition from extensile bundles to contractile asters in a minimal reconstituted system composed of stabilized microtubules, depletant, adenosine 5'-triphosphate (ATP), and clusters of kinesin-1 motors. We show that the microtubule-binding and unbinding kinetics of highly processive motor clusters set their ability to end-accumulate, which can drive polarity sorting of the microtubules and aster formation. We further demonstrate that the microscopic time scale of end-accumulation sets the emergent time scale of aster formation. Finally, we show that biochemical regulation is insufficient to fully explain the transition as generic aligning interactions through depletion, cross-linking, or excluded volume interactions can drive bundle formation despite end-accumulating motors. The extensile-to-contractile transition is well captured by a simple self-assembly model where nematic and polar aligning interactions compete to form either bundles or asters. Starting from a five-dimensional organization phase space, we identify a single control parameter given by the ratio of the different component concentrations that dictates the material-scale organization. Overall, this work shows that the interplay of biochemical and mechanical tuning at the microscopic level controls the robust self-organization of active cytoskeletal materials., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: Smoking may influence measured IOP through an effect on corneal biomechanics, but it is unclear whether this factor translates into an increased risk for glaucoma. This study aimed to examine the association of cigarette smoking with corneal biomechanical properties and glaucoma-related traits, and to probe potential causal effects using Mendelian randomization (MR)., Methods: Cross-sectional analyses within the UK Biobank (UKB) and Canadian Longitudinal Study on Aging (CLSA) cohorts. Multivariable linear and logistic regression models were used to assess associations of smoking (status, intensity, and duration) with corneal hysteresis (CH), corneal resistance factor, IOP, inner retinal thicknesses, and glaucoma. Two-sample MR analyses were performed., Results: Overall, 68,738 UKB (mean age, 56.7 years; 54.7% women) and 22 845 CLSA (mean age, 62.7 years; 49.1% women) participants were included. Compared with nonsmokers, smokers had a higher CH (UKB, +0.48 mm Hg; CLSA, +0.57 mm Hg; P < 0.001) and corneal resistance factor (UKB, +0.47 mm Hg; CLSA, +0.60 mm Hg; P < 0.001) with evidence of a dose-response effect in both studies. Differential associations with Goldmann-correlated IOP (UKB, +0.25 mm Hg; CLSA, +0.36 mm Hg; P < 0.001) and corneal-compensated IOP (UKB, -0.28 mm Hg; CLSA, -0.32 mm Hg; P ≤ 0.001) were observed. Smoking was not associated with inner retinal thicknesses or glaucoma status in either study. MR provided evidence for a causal effect of smoking on corneal biomechanics, especially higher CH., Conclusions: Cigarette smoking seems to increase corneal biomechanical resistance to deformation, but there was little evidence to support a relationship with glaucoma. This outcome may result in an artefactual association with measured IOP and could account for discordant results with glaucoma in previous epidemiological studies.

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.)

Purpose: To assess the role of static and dynamic ocular biometric parameters measured in the dark and light for predicting progression of primary angle closure suspect (PACS) to primary angle closure (PAC)., Design: Retrospective cohort study using prospective randomized controlled trial data from untreated, control eyes., Methods: Zhongshan Angle Closure Prevention Trial subjects underwent anterior segment optical coherence tomography (AS-OCT) imaging in the dark and light. Static biometric parameters were measured, consisting of angle, iris, lens, and anterior chamber parameters. Dynamic change parameters were calculated by subtracting light measurements from dark measurements. Cox proportional hazards regression models were developed to assess risk factors for PACD progression., Results: A total of 861 eyes of 861 participants were analyzed (36 progressors). On univariable analysis, TISA500 measurements in the light and dark were associated with progression (P < .001), whereas dynamic change parameters were not (P ≥ .08). In the primary multivariable model, older age (hazard ratio [HR] = 1.09 per year), higher intraocular pressure (IOP) (HR = 1.13 per mm Hg), and smaller TISA500 in the light (HR = 1.28 per 0.01 mm 2 ) were significantly associated with greater risk of progression (P ≤ .04). Dark TISA500 had similar significance (HR = 1.28, P = .002) when replacing light TISA500. Risk of progression was more predictive among eyes in the lowest quartile of light TISA500 measurements (HR = 4.56, P < .001) compared to dark measurements (HR = 2.89, P = .003)., Conclusion: Static parameters measured in the light are as predictive, and possibly more so, of angle closure progression as those measured in the dark. Ocular biometrics measured under light and dark conditions may provide additional information for risk-stratifying patients for angle closure progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background/aims: To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population., Methods: We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis., Results: Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication., Conclusion: Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Cadaveric studies have shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with Parkinson disease (PD); however, it remains unclear whether this can be reliably detected with in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed the association of these markers with the development of PD using a prospective research cohort., Methods: This cross-sectional analysis used data from 2 studies. For the detection of retinal markers in prevalent PD, we used data from AlzEye, a retrospective cohort of 154,830 patients aged 40 years and older attending secondary care ophthalmic hospitals in London, United Kingdom, between 2008 and 2018. For the evaluation of retinal markers in incident PD, we used data from UK Biobank, a prospective population-based cohort where 67,311 volunteers aged 40-69 years were recruited between 2006 and 2010 and underwent retinal imaging. Macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses were extracted from fovea-centered OCT. Linear mixed-effects models were fitted to examine the association between prevalent PD and retinal thicknesses. Hazard ratios for the association between time to PD diagnosis and retinal thicknesses were estimated using frailty models., Results: Within the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 ± 13.5 years, 51.7% female). Individuals with prevalent PD had thinner GCIPL (-2.12 μm, 95% CI -3.17 to -1.07, p = 8.2 × 10 -5 ) and INL (-0.99 μm, 95% CI -1.52 to -0.47, p = 2.1 × 10 -4 ). The UK Biobank included 50,405 participants (mean age 56.1 ± 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2,653 ± 851 days. Thinner GCIPL (hazard ratio [HR] 0.62 per SD increase, 95% CI 0.46-0.84, p = 0.002) and thinner INL (HR 0.70, 95% CI 0.51-0.96, p = 0.026) were also associated with incident PD., Discussion: Individuals with PD have reduced thickness of the INL and GCIPL of the retina. Involvement of these layers several years before clinical presentation highlight a potential role for retinal imaging for at-risk stratification of PD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Angle-closure is responsible for half of all glaucoma blindness globally. Patients with suspected glaucoma require assessment of the drainage angle by an experienced clinician. The goal of this study is to evaluate the diagnostic performance and cost-effectiveness of two non-contact tests, anterior segment OCT (Optical Coherence Tomography) (AS-OCT) and limbal anterior chamber depth for patients referred to hospital with suspected angle closure compared with gonioscopy by ophthalmologist., Methods and Analysis: Study design: prospective, multicentre, cross-sectional diagnostic accuracy study., Inclusion Criteria: adults referred from community optometry to hospital with suspected angle closure., Primary Outcome: Sensitivity and specificity., Secondary Outcomes: Positive/negative likelihood ratios, concordance, cost-effectiveness, proportion of patients requiring subsequent clinical assessment by ophthalmologist., Sample Size: 600 individuals who have been referred with suspected angle closure from primary care (community optometry). We will have a 95% probability of detecting the true sensitivity of either test to within ±3.5% based on a sensitivity of 90%. The study would also have a 95% probability of detecting the true specificity of either test to within ±5%, assuming a specificity of 75%., Ethics and Dissemination: Ethical Review Board approval was obtained. REC reference: 22/LO/0885. Our findings will be disseminated to those involved in eye care services. We will have a knowledge exchange event at the end of the study, published via the Health Technology Assessment web page and in specialist journals. The results will be presented at professional conferences and directly to patients via patient group meetings and the Glaucoma UK charity., Trial Registration Number: ISRCTN15115867., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Magnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, a few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions., Procedures: Six users (3 from each institute) imaged a known amount of Vivotrax + (10 μg Fe), diluted in a small (10 μL) or large (500 μL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users × triplicate samples × 2 sample volumes × 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax + quantification, and ROI selection were compared across users, within and across institutions., Results: MPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax + . Overall quantification yielded measurements that were within [Formula: see text] 20% from ground truth; however, SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples., Conclusions: This study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental setup, image acquisition parameters, and ROI selection analysis., (© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Importance: Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies., Objective: To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants., Design, Setting, and Participants: This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023., Exposure: Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse., Main Outcomes and Measures: The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively., Results: This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 μm [95% CI, -0.54 to -0.15 μm]; P = .001) and mRNFL (-0.16 μm [95% CI, -0.30 to -0.02 μm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84)., Conclusions and Relevance: In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

Purpose: To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR)., Design: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia., Participants: UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n = 94 206 and n = 27 777, respectively), macular inner retinal OCT measurements (n = 36 274 and n = 9991, respectively), and glaucoma status (n = 86 803 and n = 23 556, respectively)., Methods: We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma., Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status., Results: In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by +0.57 μm (P < 0.001) and +0.42 μm (P = 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of +0.08 mmHg (P = 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome., Conclusions: Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Glaucoma, the leading cause of irreversible blindness worldwide, is a complex human disease, with both genetic and environmental determinants. The availability of large-scale, population-based cohorts and biobanks, combining genotyping and detailed phenotyping, has greatly accelerated research into the aetiology of glaucoma in recent years. Hypothesis-free genome-wide association studies have furthered our understanding of the complex genetic architecture underpinning the disease, while epidemiological studies have provided advances in the identification and characterisation of environmental risk factors. It is increasingly recognised that the combined effects of genetic and environmental factors may confer a disease risk that reflects a departure from the simple additive effect of the two. These gene-environment interactions have been implicated in a host of complex human diseases, including glaucoma, and have several important diagnostic and therapeutic implications for future clinical practice. Importantly, the ability to modify the risk associated with a particular genetic makeup promises to lead to personalised recommendations for glaucoma prevention, as well as novel treatment approaches in years to come. Here we provide an overview of genetic and environmental risk factors for glaucoma, as well as reviewing the evidence and discussing the implications of gene-environment interactions for the disease., Competing Interests: Declaration of competing interest KVS: none. LRP: Consultant: Twenty Twenty, Eyenovia, Bio Character, Skye Biosciences. JHK: Grant: Pfizer, Inc. PJF: Consultant: Alphasights, GLG, Google Health, Guidepoint, PwC, Santen. APK: Consultant or lecturer: Abbvie, Aerie, Allergan, Google Health, Heidelberg Novartis, Reichert, Santen, Thea., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aims: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS., Methods: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery., Results: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59±5 years, 83% female). At 72 months, treated eyes had slightly higher average nuclear grades (p<0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2% in LPI vs 19.4% in control, p=0.401) or cataract surgery (1% for both). While LPI-treated eyes had a 10% higher risk of progression over 6 years (HR=1.10 (95% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43)., Conclusion: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time., Trial Registration Number: ISRCTN45213099., Competing Interests: Competing interests: DS-TC and JAK are employees of Genentech Inc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication., Objective: To evaluate phenotypic features across genetic burden for POAG., Design, Setting, and Participants: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023., Main Outcomes and Measures: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits., Results: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 μm and macular ganglion cell complex (GCC) of 0.26 μm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001)., Conclusion and Relevance: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.

Purpose: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population., Design: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium., Participants: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants., Methods: We examined associations of 4 categories of systemic medications-antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only., Main Outcome Measures: Glaucoma prevalence and IOP., Results: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic β-blockers (β coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP., Conclusions: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Despite widespread study of dendritic cell (DC)-based cancer immunotherapies, the in vivo postinjection fate of DC remains largely unknown. Due in part to a lack of quantifiable imaging modalities, this is troubling as the amount of DC migration to secondary lymphoid organs correlates with therapeutic efficacy. Magnetic particle imaging (MPI) has emerged as a suitable modality to quantify in vivo migration of superparamagnetic iron oxide (SPIO)-labeled DC. Herein, we describe a popliteal lymph node (pLN)-focused MPI scan to quantify DC in vivo migration accurately and consistently., Methods: Adenovirus (Ad)-transduced SPIO + (Ad SPIO + ) and SPIO + C57BL/6 bone marrow-derived DC were generated and assessed for viability and phenotype, then fluorescently labeled and injected into mouse hind footpads (n = 6). Two days later, in vivo DC migration was quantified using whole animal, pLN-focused, and ex vivo pLN MPI scans., Results: No significant differences in viability, phenotype and in vivo pLN migration were noted for Ad SPIO + and SPIO + DC. Day 2 pLN-focused MPI quantified DC migration in all instances while whole animal MPI only quantified pLN migration in 75% of cases. Ex vivo MPI and fluorescence microscopy confirmed that pLN MPI signal was due to originally injected Ad SPIO + and SPIO + DC., Conclusion: We overcame a reported limitation of MPI by using a pLN-focused MPI scan to quantify pLN-migrated Ad SPIO + and SPIO + DC in 100% of cases and detected as few as 1000 DC (4.4 ng Fe) in vivo. MPI is a suitable preclinical imaging modality to assess DC-based cancer immunotherapeutic efficacy., Relevance Statement: Tracking the in vivo fate of DC using noninvasive quantifiable magnetic particle imaging can potentially serve as a surrogate marker of therapeutic effectiveness., Key Points: • Adenoviral-transduced and iron oxide-labeled dendritic cells are in vivo migration competent. • Magnetic particle imaging is a suitable modality to quantify in vivo dendritic cell migration. • Magnetic particle imaging focused field of view overcomes dynamic range limitation., (© 2023. The Author(s).)

Purpose: This study aimed to evaluate the efficacy of laser peripheral iridotomy (LPI) prophylaxis for patients with primary angle-closure suspect (PACS) after 14 years and to identify risk factors for the conversion from PACS to primary angle closure (PAC)., Design: Extended follow-up of the Zhongshan Angle-Closure Prevention Study., Participants: Eight hundred eighty-nine Chinese patients 50 to 70 years of age with bilateral PACS., Methods: Each patient received LPI in 1 randomly selected eye, with the fellow untreated eye serving as a control. Because the risk of glaucoma was low and acute angle closure (AAC) occurred only rarely, the follow-up was extended to 14 years despite substantial benefits of LPI reported after the 6-year visit., Main Outcome Measures: Incidence of PAC, a composite end point including peripheral anterior synechiae, intraocular pressure (IOP) of > 24 mmHg, or AAC., Results: During the 14 years, 390 LPI-treated eyes and 388 control eyes were lost to follow-up. A total of 33 LPI-treated eyes and 105 control eyes reached primary end points (P < 0.01). Within them, 1 LPI-treated eye and 5 control eyes progressed to AAC. Primary angle-closure glaucoma was found in 2 LPI-treated eyes and 4 control eyes. The hazard ratio for progression to PAC was 0.31 (95% confidence interval, 0.21-0.46) in LPI-treated eyes compared with control eyes. At the 14-year visit, LPI-treated eyes showed more severe nuclear cataract, higher IOP, and larger angle width and limbal anterior chamber depth (LACD) than control eyes. Higher IOP, shallower LACD, and greater central anterior chamber depth (CACD) were associated with an increased risk of end points developing in control eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI., Concluions: Despite a two-third decrease in PAC occurrence after LPI, the cumulative risk of progression was relatively low in the community-based PACS population over 14 years. Apart from IOP, IOP elevation after DRPPT, CACD, and LACD, more risk factors are needed to achieve precise prediction of PAC occurrence and to guide clinical practice., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: To assess baseline ocular parameters in the prediction of long-term intraocular pressure (IOP) control after clear lens extraction (CLE) or laser peripheral iridotomy (LPI) in patients with primary angle closure (PAC) disease using data from the Effectiveness of Early Lens Extraction for the treatment of primary angle-closure glaucoma (EAGLE) tria., Methods: This study is a secondary analysis of EAGLE data where we define the primary outcome of 'good responders' as those with IOP<21 mm Hg without requiring additional surgery and 'optimal responders' as those who in addition were medication free, at 36-month follow-up. Primary analysis was conducted using a multivariate logistic regression model to assess how randomised interventions and ocular parameters predict treatment response., Results: A total of 369 patients (182 in CLE arm and 187 in LPI arm) completed the 36-month follow-up examination. After CLE, 90% met our predefined 'good response' criterion compared with 67% in the LPI arm, and 66% met 'optimal response' criterion compared with 18% in the LPI arm, with significantly longer drops/surgery-free survival time (p<0.05 for all). Patients randomised to CLE (OR=10.1 (6.1 to 16.8)), Chinese (OR=2.3 (1.3 to 3.9)), and those who had not previously used glaucoma drops (OR=2.8 (1.6 to 4.8)) were more likely to maintain long-term optimal IOP response over 36 months., Conclusion: Patients with primary angle closure glaucoma/PAC are 10 times more likely to maintain drop-free good IOP control with initial CLE surgery than LPI. Non-Chinese ethnicity, higher baseline IOP and using glaucoma drops prior to randomisation are predictors of worse long-term IOP response., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Patients with acute gout are frequently treated in the emergency department (ED) and represent a typically underresourced and understudied population. A key limitation for gout research in the ED is the timely ability to identify acute gout patients. Our goal was to refine a multicriteria, electronic medical record alert for gout flares and to determine its diagnostic characteristics in the ED., Methods: The gout flare alert used electronic medical record data from ED nursing notes and was triggered by the term 'gout' preceding past medical history in the chief complaint, the term 'gout' and a musculoskeletal problem in the chief complaint, or the term 'gout' in the problem list and a musculoskeletal chief complaint. We validated its diagnostic properties to assess presence/absence of gout through manual medical record review using adjudicated expert consensus as the gold standard., Results: In January 2020, we analyzed 202 patient records from 2 university-based EDs; from these records, 57 patients were identified by our gout flare alert, and 145 were identified by other means as potentially having an acute gout flare. The gout flare alert's positive predictive value was 47% (95% confidence interval [95% CI] 34-60%), negative predictive value was 94% (95% CI 90-98%), sensitivity was 75% (95% CI 61-89%), and specificity was 82% (95% CI 76-88%). The diagnostic properties were similar at both institutions., Conclusion: Our multicomponent gout flare alert had reasonable sensitivity and specificity, albeit a modest positive predictive value. An electronic gout flare alert may help enable the conduct of gout research in the ED setting., (© 2022 American College of Rheumatology.)

Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects., Design: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia., Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407)., Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses., Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma., Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (P interaction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness., Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/objectives: This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009-2010, and to characterise individuals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy., Methods: Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD; either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features; photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms; either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements., Results: Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension., Conclusions: This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health., (© 2022. The Author(s).)