Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration.

Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents a challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds of developing AMD.

Impacts on study design when implementing digital measures in Parkinson's disease-modifying therapy trials.

Introduction: Parkinson's Disease affects over 8.5 million people and there are currently no medications approved to treat underlying disease. Clinical trials for disease modifying therapies (DMT) are hampered by a lack of sufficiently sensitive measures to detect treatment effect.

Retinal perivascular macrophages regulate immune cell infiltration during neuroinflammation in mouse models of ocular disease.

The blood-retina barrier (BRB), which is disrupted in diabetic retinopathy (DR) and uveitis, is an important anatomical characteristic of the retina, regulating nutrient, waste, water, protein, and immune cell flux. The BRB is composed of endothelial cell tight junctions, pericytes, astrocyte end feet, a collagen basement membrane, and perivascular macrophages. Despite the importance of the BRB, retinal perivascular macrophage function remains unknown.

Retinal microglia express more MHC class I and promote greater T-cell-driven inflammation than brain microglia.

Introduction: Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments differ. Utilizing single-cell RNA sequencing (scRNA-seq) data from mice, we tested the hypothesis that retinal and brain microglia exhibit distinct transcriptional profiles due to their unique microenvironments.

Association between macrophage-like cell density and ischemia metrics in diabetic eyes.

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.

Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.

Purpose: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs).

Methods: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes.

Exploring Diagnostic Precision and Triage Proficiency: A Comparative Study of GPT-4 and Bard in Addressing Common Ophthalmic Complaints.

In the modern era, patients often resort to the internet for answers to their health-related concerns, and clinics face challenges to providing timely response to patient concerns. This has led to a need to investigate the capabilities of AI chatbots for ophthalmic diagnosis and triage. In this in silico study, 80 simulated patient complaints in ophthalmology with varying urgency levels and clinical descriptors were entered into both ChatGPT and Bard in a systematic 3-step submission process asking chatbots to triage, diagnose, and evaluate urgency.

Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator.

The management of preretinal fibrovascular membranes, a devastating complication of advanced diabetic retinopathy (DR), remains challenging. We characterized the molecular profile of cell populations in these fibrovascular membranes to identify potentially new therapeutic targets. Preretinal fibrovascular membranes were surgically removed from patients and submitted for single-cell RNA-Seq (scRNA-Seq).

NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration.

Background: Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1 mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes.

Thrombospondin-1 proteomimetic polymers exhibit anti-angiogenic activity in a neovascular age-related macular degeneration mouse model.

Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the developed world. Current therapy includes monthly intraocular injections of anti-VEGF antibodies, which are ineffective in up to one third of patients. Thrombospondin-1 (TSP1) inhibits angiogenesis via CD36 binding, and its down-regulated expression is negatively associated with the onset of nAMD.

Multi-Modality, Multi-Dimensional Characterization of Pediatric Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease is a multifaceted disease that progresses through multiple phases; it involves metabolic as well as structural changes. These alterations can be measured directly or indirectly through blood, non-invasive imaging, and/or tissue analyses. While some studies have evaluated the correlations between two sets of measurements (e.

Prevalence of Retinal Venous Malformations in Patients With Cerebral Cavernous or Arteriovenous Malformations.

Background: Cerebral vascular malformations (CVMs) may result in hemorrhage, seizure, neurologic dysfunction, and death. CVMs include capillary telangiectasias, venous malformations, cavernous malformations, and arteriovenous malformations. Cavernous and arteriovenous malformations carry the highest risk of complications.

Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration.

Objective: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD).

Design: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1-2) and case-control analysis in the Merative MarketScan Research Databases (#3).

Participants: Eyes with neovascular AMD and 2 years of follow-up (#1).

Methods for Imaging Inflammation and Transendothelial Migration in Vivo and ex Vivo.

Inflammation is the body's response to injury and harmful stimuli and contributes to a range of infectious and noninfectious diseases. Inflammation occurs through a series of well-defined leukocyte-endothelial cell interactions, including rolling, activation, adhesion, transmigration, and subsequent migration through the extracellular matrix. Being able to visualize the stages of inflammation is important for a better understanding of its role in diseases processes.

CD11c+ macrophages are proangiogenic and necessary for experimental choroidal neovascularization.

Patients with neovascular AMD (nAMD) suffer vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Macrophages are found in CNV lesions from patients with nAMD. Additionally, Ccr2-/- mice, which lack classical monocyte-derived macrophages, show reduced CNV size.

Macrophage-like Cells Are Increased in Retinal Vein Occlusion and Correlate with More Intravitreal Injections and Worse Visual Acuity Outcomes.

Macrophage-like cells (MLCs) are an emerging retinal biomarker. MLCs are increased in retinal vein occlusion (RVO) eyes, but their predictive value is unknown. This study investigated if MLCs can predict meaningful clinical outcomes.

Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease.

Background & Aims: Despite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological features of NAFLD.

Methods: Using modified-aptamer proteomics, we assayed 5,220 proteins in each of 2,852 single serum samples from 636 individuals with histologically confirmed NAFLD.

Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis.

Background & Aims: Non-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement.

Methods: Adult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76).

Angiopoietin-1 Is Required for Vortex Vein and Choriocapillaris Development in Mice.

Background: The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid.

Methods: Using neural crest-specific knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning.

Magnetic Resonance Imaging to Assess Body Composition Change in Adolescents With Obesity After Sleeve Gastrectomy.

Objectives: Metabolic and bariatric surgery is the most effective weight loss treatment for severe obesity. The number of adolescents undergoing sleeve gastrectomy is increasing. We investigated changes in body composition in adolescents undergoing sleeve gastrectomy 12-26 weeks post-operatively using whole-body magnetic resonance imaging (WB-MRI).

Macrophages in close proximity to the vitreoretinal interface are potential biomarkers of inflammation during retinal vascular disease.

Background: Diabetic retinopathy and retinal vein occlusion are vision threatening retinal vascular diseases. Current first-line therapy targets the vascular component, but many patients are treatment-resistant due to unchecked inflammation. Non-invasive inflammatory imaging biomarkers are a significant unmet clinical need for patients.

Randomized placebo-controlled trial of losartan for pediatric NAFLD.

Background And Aims: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

Approach And Results: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020).