Endophthalmitis Rates and Types of Treatments After Intraocular Procedures.

Importance: Long-term trend analyses of overall endophthalmitis rates and treatment patterns are scarce. It is also unknown if the deviation from the recommendations of the Endophthalmitis Vitrectomy Study toward decreased utilization of vitrectomy is associated with different vision outcomes.

Objective: To determine whether the rate of endophthalmitis after intraocular procedures or the primary treatment (prompt vitrectomy vs tap and inject) for endophthalmitis has changed over the past 20 years.

Do Treatment Patterns for Endophthalmitis after Cataract Surgery Follow the Endophthalmitis Vitrectomy Study Recommendations?: An Academy IRIS® Registry Analysis.

Objective: To evaluate whether treatment patterns for endophthalmitis after cataract surgery in American Academy of Ophthalmology IRIS® (Intelligent Research in Sight) Registry patients are in line with evidence-based guidelines established by the 1995 Endophthalmitis Vitrectomy Study (EVS), which showed that patients who present with light perception (LP) vision have better visual outcomes with immediate vitrectomy (VIT) compared with vitreous tap with antibiotic injection (TAP).

Design: Retrospective cohort study.

Subjects: Intelligent Research in Sight Registry patients undergoing cataract surgery between 2014 and 2022 (identified by Current Procedural Terminology codes), presenting with endophthalmitis (identified by International Classification of Diseases 10 codes) within 42 days postcataract surgery, and having a record of being treated with VIT or TAP on the same or 1 day after endophthalmitis diagnosis were identified.

Trends and Sociodemographic Patterns in Keratoconus Management 2015-2020: An American Academy of Ophthalmology IRIS® Registry Analysis.

Purpose: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age from 2015 to 2020 and evaluate sociodemographic associations with the treatment approach.

Design: Retrospective cohort study.

Participants: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS® Registry (Intelligent Research in Sight).

Disparities in Retinal Vein Occlusion Presentation and Initiation of Anti-VEGF Therapy: An Academy IRIS® Registry Analysis.

Objective: Investigate disparities in retinal vein occlusion (RVO) presentation and initiation of anti-VEGF treatment.

Design: Retrospective cohort study.

Subjects: Patients in the American Academy of Ophthalmology IRIS® (Intelligent Research in Sight) Registry database (2015-2021) with branch or central RVO and macular edema (ME).

Investigating clot-flow interactions by integrating intravital imaging with in silico modeling for analysis of flow, transport, and hemodynamic forces.

As a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge.

Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS Registry Experience.

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition.

Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed.

Incidence and Risk Factors for Retinal Detachment and Retinal Tear after Cataract Surgery: IRIS® Registry (Intelligent Research in Sight) Analysis.

Objective: To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).

Design: Retrospective cohort study.

Participants: Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017.

Open-Globe Injury Repairs in the American Academy of Ophthalmology IRIS® Registry 2014 - 2018: Incidence, Risk Factors, and Visual Outcomes.

Purpose: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS® Registry (Intelligent Research in Sight).

Design: Retrospective cohort study.

Participants: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry.

GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12.

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis.

Thrombin spatial distribution determines protein C activation during hemostasis and thrombosis.

Rebalancing the hemostatic system by targeting endogenous anticoagulant pathways, like the protein C (PC) system, is being tested as a means of improving hemostasis in patients with hemophilia. Recent intravital studies of hemostasis demonstrated that, in some vascular contexts, thrombin activity is sequestered in the extravascular compartment. These findings raise important questions about the context-dependent contribution of activated PC (APC) to the hemostatic response, because PC activation occurs on the surface of endothelial cells.

The contribution of TFPIα to the hemostatic response to injury in mice.

Background: Tissue factor pathway inhibitor (TFPI) is an essential regulator of coagulation, limiting thrombin generation and preventing thrombosis. In humans and mice, TFPIα is the sole isoform present in platelets.

Objective: Here, we asked whether TFPIα, because of its release from platelets at sites of injury, has a unique role in limiting the hemostatic response.

A Human Vascular Injury-on-a-Chip Model of Hemostasis.

Hemostasis is an innate protective mechanism that plays a central role in maintaining the homeostasis of the vascular system during vascular injury. Studying this essential physiological process is often challenged by the difficulty of modeling and probing the complex dynamics of hemostatic responses in the native context of human blood vessels. To address this major challenge, this paper describes a microengineering approach for in vitro modeling of hemostasis.

Use of electron microscopy to study platelets and thrombi.

Electron microscopy has been a valuable tool for the study of platelet biology and thrombosis for more than 70 years. Early studies using conventional transmission and scanning electron microscopy (EM) provided a foundation for our initial understanding of platelet structure and how it changes upon platelet activation. EM approaches have since been utilized to study platelets and thrombi in the context of basic, translational and clinical research, and they are instrumental in the diagnosis of multiple platelet function disorders.

Interrelationships between structure and function during the hemostatic response to injury.

Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo.

Detection of Sub-fM DNA with Target Recycling and Self-Assembly Amplification on Graphene Field-Effect Biosensors.

All-electronic DNA biosensors based on graphene field-effect transistors (GFETs) offer the prospect of simple and cost-effective diagnostics. For GFET sensors based on complementary probe DNA, the sensitivity is limited by the binding affinity of the target oligonucleotide, in the nM range for 20 mer targets. We report a ∼20 000× improvement in sensitivity through the use of engineered hairpin probe DNA that allows for target recycling and hybridization chain reaction.

Regulation of Platelet Activation and Coagulation and Its Role in Vascular Injury and Arterial Thrombosis.

Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury. Dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is robust. Studies have elucidated the major molecular signaling pathways responsible for platelet activation and aggregation.

Minimum wound size for clotting: flowing blood coagulates on a single collagen fiber presenting tissue factor and von Willebrand factor.

It is unknown if a lower size limit exists for human blood coagulation under flow over physiological vessel wall triggers as small as a single collagen fiber. Prior determinations of the smallest sized surface stimuli necessary for clotting of human blood, defined as the patch size threshold, have not deployed whole blood, hemodynamic flow, and platelet adhesive stimuli. For whole blood perfused in microfluidic devices, we report that steady venous flow (wall shear rate, 100 s(-1)) was sufficient to drive platelet deposition on 20 micron long zones of collagen fibers or on a single fiber.

Computational identification and analysis of signaling subnetworks with distinct functional roles in the regulation of TNF production.

Inflammation is a complex process driven by the coordinated action of a vast number of pro- and anti-inflammatory molecular mediators. While experimental studies have provided an abundance of information about the properties and mechanisms of action of individual mediators, essential system-level regulatory patterns that determine the time-course of inflammation are not sufficiently understood. In particular, it is not known how the contributions from distinct signaling pathways involved in cytokine regulation combine to shape the overall inflammatory response over different time scales.

A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity.

Hemostatic thrombi formed after a penetrating injury have a distinctive structure in which a core of highly activated, closely packed platelets is covered by a shell of less-activated, loosely packed platelets. We have shown that differences in intrathrombus molecular transport emerge in parallel with regional differences in platelet packing density and predicted that these differences affect thrombus growth and stability. Here we test that prediction in a mouse vascular injury model.

A systems approach to hemostasis: 2. Computational analysis of molecular transport in the thrombus microenvironment.

Hemostatic thrombi formed after a penetrating injury have a heterogeneous architecture in which a core of highly activated, densely packed platelets is covered by a shell of less-activated, loosely packed platelets. In the first manuscript in this series, we show that regional differences in intrathrombus protein transport rates emerge early in the hemostatic response and are preserved as the thrombus develops. Here, we use a theoretical approach to investigate this process and its impact on agonist distribution.

A systems approach to hemostasis: 1. The interdependence of thrombus architecture and agonist movements in the gaps between platelets.

Hemostatic thrombi develop a characteristic architecture in which a core of highly activated platelets is covered by a shell of less-activated platelets. Here we have used a systems biology approach to examine the interrelationship of this architecture with transport rates and agonist distribution in the gaps between platelets. Studies were performed in mice using probes for platelet accumulation, packing density, and activation plus recently developed transport and thrombin activity probes.

Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function.

Background: Hemorrhagic shock is a leading cause of death following severe trauma, and platelet transfusions are frequently necessary to achieve hemostasis. Platelets, however, require special storage conditions, and storage time has been associated with loss of platelet quality. We hypothesized that standard storage conditions have a deleterious effect on platelet mitochondrial function and platelet activation.

Harnessing the platelet signaling network to produce an optimal hemostatic response.

Once released into the circulation by megakaryocytes, circulating platelets can undergo rapid activation at sites of vascular injury and resist unwarranted activation, which can lead to heart attacks and strokes. Historically, the signaling mechanisms underlying the regulation of platelet activation have been approached as a collection of individual pathways unique to agonist. This review takes a different approach, casting platelet activation as the product of a signaling network, in which activating and restraining mechanisms interact in a flexible network that regulates platelet adhesiveness, cohesion between platelets, granule secretion, and the formation of a stable hemostatic thrombus.