Identification of Retinal Amyloid-Beta in Ex-Vivo Human Glaucoma Eyes Using a Novel Ocular Tracer.

PURPOSE: To characterize the presence of amyloid-beta (Aß) in human glaucoma retina and to test identification of retinal Aß using a novel fluorescent Aß-binding small molecule (AMDX-2011). METHODS: Post-mortem human eyes with (n=4) and without (n=4) glaucoma were acquired from an eye bank. Retinas were dissected, flat-mounted, and fixed. Using the flat-mounts, immunofluorescence was performed against Aß, AMDX-2011 staining was conducted, and images were acquired using fluorescence microscopy. RESULTS: Fluorescence microscopy demonstrated presence of Aß signal that co-localized with AMDX-2011 staining in glaucoma retina. Co-labeled puncta appeared in all quadrants of the retina, including retina temporal to the optic nerve. The puncta were mainly located within the inner layers of the retina. Glaucoma retinas had more co-labeled puncta than control retinas in all locations (P = 0.002-0.02). Co-labeled puncta were also larger in the superior quadrant of glaucoma compared to control retinas (P = 0.02). CONCLUSIONS: Aß was detected in human glaucomatous retina, and its distribution was mapped. AMDX-2011 identification of Aß may lead to future diagnostic tests aimed at detecting Aß in glaucoma patients.

Preclinical lentiviral vector-mediated hematopoietic stem and progenitor cell gene therapy corrects Pompe disease-related muscle and neurological manifestations.

Pompe disease, a rare genetic neuromuscular disorder, is caused by a deficiency of acid alpha-glucosidase (GAA), leading to an accumulation of glycogen in lysosomes, and resulting in the progressive development of muscle weakness. The current standard treatment, enzyme replacement therapy (ERT), is not curative and has limitations such as poor penetration into skeletal muscle and both the central and peripheral nervous systems, a risk of immune responses against the recombinant enzyme, and the requirement for high doses and frequent infusions. To overcome these limitations, lentiviral vector-mediated hematopoietic stem and progenitor cell (HSPC) gene therapy has been proposed as a next-generation approach for treating Pompe disease. This study demonstrates the potential of lentiviral HSPC gene therapy to reverse the pathological effects of Pompe disease in a preclinical mouse model. It includes a comprehensive safety assessment via integration site analysis, along with single-cell RNA sequencing analysis of central nervous tissue samples to gain insights into the underlying mechanisms of phenotype correction.

Overview of cardiac toxicity from radiation therapy.

Radiotherapy is an essential part of treatment for many patients with thoracic cancers. However, proximity of the heart to tumour targets can lead to cardiac side effects, with studies demonstrating link between cardiac radiation dose and adverse outcomes. Although reducing cardiac dose can reduce associated risks, most cardiac constraint recommendations in clinical use are generally based on dose to the whole heart, as dose assessment at cardiac substructure levels on individual patients has been limited historically. Furthermore, estimation of an individual's cardiac risk is complex and multifactorial, which includes radiation dose alongside baseline risk factors, and the impact of systemic therapies. This review gives an overview of the epidemiological impact of cancer and cardiac disease, risk factors contributing to radiation-related cardiotoxicity, the evidence for cardiac side effects and future directions in cardiotoxicity research. A better understanding of the interactions between risk factors, balancing treatment benefit versus toxicity and the ongoing management of cardiac risk is essential for optimal clinical care. The emerging field of cardio-oncology is thus a multidisciplinary collaborative effort to enable better understanding of cardiac risks and outcomes for better-informed patient management decisions.

Cathepsin B Nuclear Flux in a DNA-Guided "Antinuclear Missile" Cancer Therapy.

Some antinuclear antibodies (ANAs) bind extracellular nucleic acids released into tumor environments and are pulled into the nuclei of live cancer cells through nucleoside salvage pathways, independent of tumor-specific surface antigens. Here we show that ANA nuclear penetration induces nuclear flux by the lysosomal protease cathepsin B and leverage this mechanism to design an antinuclear antibody-drug conjugate (ANADC) with cathepsin B-labile drug linker. The ANADC targets nucleic acid exhaust from necrotic tumors and crosses membrane barriers through nucleoside salvage as a DNA-seeking and tumor agnostic "antinuclear missile" cancer therapy.

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change: GLP-1 Receptor Agonists and Intraocular Pressure Change.

OBJECTIVE: This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). DESIGN: Retrospective clinical cohort study. SETTING: Multicenter. STUDY POPULATION: 1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics. OBSERVATION PROCEDURES: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ∆IOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. MAIN OUTCOME MEASURES: Primary outcome measure was ∆IOP after exposure to the medication. RESULTS: The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ∆IOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. CONCLUSIONS: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

Reference Database for a Novel Binocular Visual Function Perimeter: A Randomized Clinical Trial.

Purpose: To construct a comprehensive reference database (RDB) for a novel binocular automated perimeter. Design: A four-site prospective randomized clinical trial. Subjects and Controls: Three hundred fifty-six healthy subjects without ocular conditions that might affect visual function were categorized into 7 age groups. Methods: Subjects underwent comprehensive ocular examination of both eyes before enrollment. Using the TEMPO/IMOvifa automated perimeter (Topcon Healthcare/CREWT Medical Systems), each subject completed 4 binocular threshold visual field (VF) tests during a single visit: First, practice 24-2 and 10-2 tests were obtained from both eyes. Next, study 24-2 and 10-2 tests were obtained from both eyes. Test order of each sequence was randomized, and the tests were conducted under standard automated perimetry testing conditions: Goldmann stimulus size III, 3183 cd/m2 maximum stimulus intensity, and background intensity of 10 cd/m2, using AIZE-Rapid test strategy. Standard VF reliability indices were assessed. For each subject, 24-2 and 10-2 test results from 1 randomly selected eye were analyzed. Main Outcome Measures: Perimetric threshold sensitivity and reference limits for each test analysis parameter. Results: The ages of the study cohort were widely distributed, with a mean age (standard deviation [SD]) of 52.3 (18.5) years. Sex assignment was 44.0% male and 56.0% female. The majority of subjects self-identified as White (67.4%), followed by Black or African American (13.5%) and Asian (8.7%), with 14.6% self-identified as Hispanic or Latino ethnicity. Mean sensitivity (SD) was 29.1 (1.3) decibels (dB) for the 24-2 and 32.4 (1.0) dB for the 10-2 test. For the 24-2 and 10-2, mean sensitivity (SD) age-related changes averaged -0.06 (0.01) dB and -0.05 (0.01) dB per year, respectively. The normal range of pointwise threshold sensitivity increased with eccentricity and showed asymmetry around the mean, particularly notable in the 24-2 test. Mean (SD) binocular test duration was 3.18 (0.38) minutes (1 minute 35 seconds per eye) for the 24-2 test and 3.58 (0.43) minutes (1 minute 47 seconds per eye) for the 10-2 test. Conclusions: An RDB for the TEMPO/IMOvifa perimeter was established, highlighting the significance of considering both age and stimulus eccentricity in interpreting threshold VF test results. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outbreak simulation on the neonatal ward using silica nanoparticles with encapsulated DNA - unmasking of key spread areas.

PURPOSE: Nosocomial infections pose a serious threat. In neonatal intensive care units (NICUs) in particular, there are repeated outbreaks caused by microorganisms without the sources or dynamics being conclusively determined. This study aims to use amorphous silica nanoparticles with encapsulated DNA (SPED) to simulate outbreak events and to visualize dissemination patterns in a NICU to gain a better understanding of these dynamics. METHODS: Three types of SPED were strategically placed on the ward to mimic three different dissemination dynamics among real-life conditions and employee activities. SPED DNA, resistant to disinfectants, was sampled at 22 predefined points across the ward for four days and qPCR analysis was conducted. RESULTS: Starting from staff areas, a rapid ward-wide SPED dissemination including numerous patient rooms was demonstrated. In contrast, a primary deployment in a patient room only led to the spread in the staff area, with no distribution in the patient area. CONCLUSION: This study pioneers SPED utilization in simulating outbreak dynamics. By unmasking staff areas as potential key trigger spots for ward-wide dissemination the revealed patterns could contribute to a more comprehensive view of outbreak events leading to rethinking of hygiene measures and training to reduce the rate of nosocomial infections in hospitals.

Relationship Between Retinal Oxygen Saturation and the Severity of Visual Field Damage in Glaucoma.

PRCIS: Increased oxygen saturation (StO 2 ) was significantly associated with the severity of visual field (VF) damage in patients with glaucoma. OBJECTIVE: To investigate the association between retinal StO 2 percentage and the severity of VF loss in glaucoma. METHODS: A total of 198 eyes from 131 patients with glaucoma were included in this cross-sectional study. Participants underwent imaging using ocular oximetry (Zilia) and 24-2 Swedish Interactive Threshold Algorithm standard VF (Carl Zeiss-Meditec). StO 2 (%) was measured at 2 locations of the peripapillary optic nerve head (superotemporal, and inferotemporal). Measurements were reported as the mean of at least 5 measurements in each location. Associations between the severity of VF loss, reported as mean deviation, and StO 2 (%) were calculated. RESULTS: A total of 198 eyes of 131 patients (mean (95% CI) age, 71.1 (68.9,73.3) years, 68 females (51.9%), and 63 males (48.1%) were analyzed. In univariable analysis, higher StO 2 -0.06 (-0.12, 0.00) was associated with severity in all hemifields ( P = 0.047). Multivariate regression analysis showed that each 1% increase in StO 2 was associated with -0.06 (-0.12, -0.00) dB loss in mean deviation in all hemifields ( P = 0.043). In multivariate regression analysis in the superior hemifields, higher StO 2 -0.07 (-0.16, 0.01) tended to be associated with superior hemifield severity ( P = 0.09). CONCLUSIONS: Retinal oximetry enabled the continuous quantitative measurement of retinal StO 2. Increased StO 2 was significantly associated with the severity of VF damage in patients with glaucoma.

The predictive value of intraoperative facial motor evoked potentials in cerebellopontine angle tumor surgery.

OBJECTIVE: Our aim is to explore the value of intraoperative facial motor evoked potentials (FMEP) for facial outcomes in cerebellopontine angle (CPA) tumor surgery to provide an evidence-based consensus standard for future clinical practice and prospective studies. METHODS: Electronic databases were searched from inception to June 2023. Study quality was assessed with the QUADAS-2 tool. Bivariate and random-effects models for meta-analysis and meta-regression generated summary receiver operating characteristic curves (ROC) and forest plots for estimates of sensitivity and specificity. RESULTS: We included 17 studies (1,206 participants). Sensitivity was lower in the immediate (IM) post-operative (0.76, 95% CI 0.65-0.84) compared to follow-up (FU) period (0.82, 95% CI 0.74-0.88) while specificity was similar in both groups (IM, 0.94, 95% CI 0.89-0.97; FU, 0.93, 95% CI 0.87-0.96). Data driven estimates improved FMEP performance but require confirmation from future studies. Amplitude cutoff criteria and studies that scored new deficits as worse than House-Brackmann (HB) grade 2 yielded best sensitivities. CONCLUSIONS: FMEP demonstrated statistically significant accuracy for facial function monitoring. Implementation of FMEPs varied widely across studies. SIGNIFICANCE: Our study is the first systematic review with meta-analysis to demonstrate that intraoperative FMEP is valuable in CPA tumor surgery for facial outcomes. Meta-regression identified the methods that were most useful in the application of FMEPs.

Time to glaucoma progression detection by optical coherence tomography and visual field in glaucoma individuals of African descent.

PURPOSE: To examine the time to glaucoma progression detection by retinal nerve fiber layer thickness (RNFLT) and visual field (VF) among African descent (AD) individuals. DESIGN: Retrospective cohort study. METHODS: Setting: Multi-center. STUDY POPULATION: We included AD glaucoma eyes from DIGS/ADAGES with ≥2-year/5-visits of optic nerve head RNFLT and 24-2 VF examinations. Intervention or Observation Procedure: Rates of VF mean deviation (MD) and RNFLT worsening were analyzed using linear mixed-effects models, and longitudinal data was simulated using the variability estimates. MAIN OUTCOME MEASURE: The simulated time to detect trend-based glaucoma progression was assessed with assumed rates of VF MD and RNFLT change derived from the cohort (25th, 50th, 75th percentile [p25, median, p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 AD subjects (mean baseline age: 63.4 years; VF MD: -4.2 dB, RNFLT: 80.2 µm). The p25, median, mean and p75 rates of change were -0.43, -1.01, -1.15 and -1.64 µm/year for RNFLT, and 0.00, -0.21, -0.30 and -0.51 dB/year for VF MD, respectively. Compared to VF MD, RNFLT showed an overall shorter mean time to progression detection (time difference: 0.4-1.7 years), with the mean rates showing the largest difference (RNFLT: 5.2 years vs. VF MD: 6.9 years). Similarly, we found an overall shorter time to detect RNFLT progression, compared to that of VF MD progression, in mild glaucoma eyes (≥1 year earlier) and in moderate-advanced glaucoma eyes (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed potentially shorter time to detect RNFLT progression than VF MD progression in AD eyes. Our findings support the importance of using RNFLT to detect progressive glaucoma in AD individuals.

A genus-specific nsp12 region impacts polymerase assembly in Alpha- and Gammacoronaviruses.

Coronavirus relevancy for human health has surged over the past 20 years as they have a propensity for spillover into humans from animal reservoirs resulting in pandemics such as COVID-19. The diversity within the Coronavirinae subfamily and high infection frequency in animal species worldwide creates a looming threat that calls for research across all genera within the Coronavirinae subfamily. We sought to contribute to the limited structural knowledge within the Gammacoronavirus genera and determined the structure of the viral core replication-transcription complex (RTC) from Infectious Bronchitis Virus (IBV) using single-particle cryo-EM. Comparison between our IBV structure with published RTC structures from other Coronavirinae genera reveals structural differences across genera. Using in vitro biochemical assays, we characterized these differences and revealed their differing involvement in core RTC formation across different genera. Our findings highlight the value of cross-genera Coronavirinae studies, as they show genera specific features in coronavirus genome replication. A broader knowledge of coronavirus replication will better prepare us for future coronavirus spillovers.

Combined high rates of alternative breeding strategies unexpectedly found among populations of a solitary nesting raptor.

Social monogamy is the prevalent mating system in birds, but alternative strategies of extra-pair paternity (EPP) and conspecific brood parasitism (CBP) occur in many species. Raptors are virtually absent in discussions of broad taxonomic reviews regarding EPP and CBP likely because these strategies are mostly absent or at low frequency; CBP is unreported in solitary nesting raptors. In contrast, we found high frequencies of EPP (16%-31%) and CBP (15%-26%) nests among three populations of Cooper's Hawks (Accipiter cooperii) across the northern breeding range of this solitary nesting, socially monogamous species. EPP and CBP combined occurred in 42%-46% of all nests among populations and hence unexpectedly were nearly equivalent to proportions of genetically monogamous nests. Select covariates failed to predict presence of EPP and CBP in part because virtually all extra-pair adults were uncaught and likely were floaters. We found no support for the hypothesis that territorial females traded copulations for food to maximize energy intake for increased production. Our unique discoveries enhance knowledge of the extent and diversity of alternative breeding strategies among groups of avian and other animal species.

Topical Tranexamic Acid on Donor Wounds in Burn Patients: A Randomized Placebo-controlled Trial.

Background: Patients with major burn injuries are prone to massive blood loss owing to tangential excision of burn wounds and donor skin harvesting. In general, topical application of the antifibrinolytic drug tranexamic acid (TXA) to surgical wounds reduces bleeding; however, its effect on bleeding and re-epithelialization in superficial wounds of burns has not been explored. Methods: This study aimed to investigate the therapeutic potential of topical TXA in reducing blood loss and its effect on wound re-epithelialization in burn surgery. Split-thickness skin graft donor wounds in burn patients were paired and randomized to topical application of either TXA (25 mg/mL) or placebo. Endpoints were postoperative bleeding as measured by dressing weight gain per cm2 wound area, blood stain area per wound area, and visual evaluation of bleeding in the dressings. Healing time was recorded to analyze the effect on wound re-epithelialization. Results: There was no significant difference in bleeding or time to re-epithelialization between the TXA and placebo wounds. A post hoc subanalysis of wounds with dressing weight gain above the median, showed a significant difference in favor of TXA. However, use of tumescence may have influenced end points. No significant adverse events related to the study drugs were observed. Conclusions: This study demonstrates that topical application of TXA (25 mg/mL) to split-thickness skin graft donor wounds does not delay re-epithelialization. Although a reduction in bleeding is suggested, further studies are needed to determine the role of topical TXA in reducing bleeding in burn surgery.

Phospholamban Cardiomyopathy Leading to Advanced Heart Failure in an Active Duty Service Member.

A phospholamban mutation is a rare genetic cause of dilated cardiomyopathy (DCM). Our case describes a young service member who presented with advanced heart failure and was found to have a familial DCM from an autosomal dominant phospholamban mutation. He ultimately underwent a successful heart transplant just 23 days after his initial presentation. This case highlights the importance of genetic screening and surveillance for patients with a family history of DCM, and it identifies a gap in medical standards for military accession.

Vascular streak dieback: A novel threat to redbud and other woody ornamental production in the United States.

Eastern redbud (Cercis canadensis L.) is a popular and high-value woody ornamental plant native to the eastern and south-central United States of America (U.S.A.). In recent years, redbud production in the Southeastern U.S.A. has been greatly affected by a novel threat: vascular streak dieback (VSD). Infected plants exhibit a common set of symptoms, including leaf scorch, tip dieback, and vascular streaking that creates a marbled pattern in stem cross-section. Based on both conventional diagnosis and molecular identification, it has been found that the fungus Ceratobasidium sp. D.P. Rogers (Csp) is consistently associated with VSD-symptomatic eastern redbuds. However, the causal agent(s) of VSD has not yet been conclusively confirmed. Although eastern redbud has been the most frequently identified host tree, more than 25 other native plant genera have been confirmed to have VSD associated with Csp. The near-obligate nature of this fungus has made it challenging to culture, extract DNA, and conduct further studies to confirm its pathogenicity. This article highlights the emerging challenges of VSD, focusing on the following: 1) the recent history of VSD; 2) the increasing importance of VSD to woody ornamental nursery production in the U.S.A.; 3) the currently available protocols for isolating, culturing, storing, and maintaining the putative causal agent; 4) the rapid molecular detection of Csp; 5) phylogenetic findings on the origin and relatedness of Csp to previously recorded diseases, especially VSD in cacao (Theobroma cacao L.); and 6) preliminary results and observations from fungicide trials and cultivar screening in Tennessee. The article also outlines research needed to comprehensively understand VSD and accelerate the development of effective management strategies.

Leading Causes of Death in the US, 2019-2023.

This Viewpoint from the National Center for Health Statistics reports the leading causes of death in the US from 2019 to 2023, including the emergence of COVID-19 and shifts in other top causes as pandemic deaths decreased.

Detection of glaucoma progression on longitudinal series of en-face macular optical coherence tomography angiography images with a deep learning model.

BACKGROUND/AIMS: To design a deep learning (DL) model for the detection of glaucoma progression with a longitudinal series of macular optical coherence tomography angiography (OCTA) images. METHODS: 202 eyes of 134 patients with open-angle glaucoma with ≥4 OCTA visits were followed for an average of 3.5 years. Glaucoma progression was defined as having a statistically significant negative 24-2 visual field (VF) mean deviation (MD) rate. The baseline and final macular OCTA images were aligned according to centre of fovea avascular zone automatically, by checking the highest value of correlation between the two images. A customised convolutional neural network (CNN) was designed for classification. A comparison of the CNN to logistic regression model for whole image vessel density (wiVD) loss on detection of glaucoma progression was performed. The performance of the model was defined based on the confusion matrix of the validation dataset and the area under receiver operating characteristics (AUC). RESULTS: The average (95% CI) baseline VF MD was -3.4 (-4.1 to -2.7) dB. 28 (14%) eyes demonstrated glaucoma progression. The AUC (95% CI) of the DL model for the detection of glaucoma progression was 0.81 (0.59 to 0.93). The sensitivity, specificity and accuracy (95% CI) of DL model were 67% (34% to 78%), 83% (42% to 97%) and 80% (52% to 95%), respectively. The AUC (95% CI) for the detection of glaucoma progression based on the logistic regression model was lower than the DL model (0.69 (0.50 to 0.88)). CONCLUSION: The optimised DL model detected glaucoma progression based on longitudinal macular OCTA images showed good performance. With external validation, it could enhance detection of glaucoma progression. TRIAL REGISTRATION NUMBER: NCT00221897.

Mortality in the United States - Provisional Data, 2023.

Final annual mortality data from the National Vital Statistics System for a given year are typically released 11 months after the end of the calendar year. Provisional data, which are based on preliminary death certificate data, provide an early estimate of deaths before the release of final data. In 2023, a provisional total of 3,090,582 deaths occurred in the United States. The age-adjusted death rate per 100,000 population was 884.2 among males and 632.8 among females; the overall rate, 750.4, was 6.1% lower than in 2022 (798.8). The overall rate decreased for all age groups. Overall age-adjusted death rates in 2023 were lowest among non-Hispanic multiracial (352.1) and highest among non-Hispanic Black or African American persons (924.3). The leading causes of death were heart disease, cancer, and unintentional injury. The number of deaths from COVID-19 (76,446) was 68.9% lower than in 2022 (245,614). Provisional death estimates provide an early signal about shifts in mortality trends. Timely and actionable data can guide public health policies and interventions for populations experiencing higher mortality.

Screening of Glaucoma: Consensus and Directions.

PURPOSE: Glaucoma is a leading public health concern globally. This summary discusses barriers to glaucoma screening and novel strategies for a cost-effective glaucoma screening. METHODS/RESULTS: We discuss barriers to glaucoma screening and recent advancements in glaucoma detection and care, including targeted screening approach as well as telemedicine, genetic testing, and artificial intelligence (AI). A major barrier to glaucoma screening is the cost-effectiveness of case finding resulting from the low prevalence of the disease and the complexity of the diagnosis. Targeted-screening, as well as multi-level screening, can reduce the false positive rate and increase the cost-effectiveness of the program. Telemedicine, availability of genetic testing and polygenic risk scores, and AI provide the opportunity for novel glaucoma screening programs in primary care, portable, and home-based settings and will be helpful for lowering the costs, identifying patients in need of urgent treatment and enabling timely diagnosis and early intervention. CONCLUSIONS: Screening of glaucoma is challenging and changing. Recent advancements in digital technology and genetics have led to the development of tools that are promising for novel screening methodologies. Clinical trials are needed to demonstrate the long-term effect of targeted screening on the burden of glaucoma worldwide.