Ex vivo modelling of cardiac injury identifies ferroptosis-related pathways as a potential therapeutic avenue for translational medicine.

BACKGROUND: Heart failure (HF) is a burgeoning health problem worldwide. Often arising as a result of cardiac injury, HF has become a major cause of mortality with limited availability of effective treatments. Ferroptotic pathways, triggering an iron-dependent form of cell death, are known to be potential key players in heart disease. This form of cell death does not exhibit typical characteristics of programmed cell death, and is mediated by impaired iron metabolism and lipid peroxidation signalling. OBJECTIVES: The aim of this study is to establish an ex-vivo model of myocardial injury in living myocardial slices (LMS) and to identify novel underlying mechanisms and potential therapeutic druggable target(s). METHODS AND RESULTS: In this study, we employed LMS as an ex vivo model of cardiac injury to investigate underlying mechanisms and potential therapeutic targets. Cryoinjury was induced in adult rat LMS, resulting in 30 % tissue damage. Cryoinjured LMS demonstrated impaired contractile function, cardiomyocyte hypertrophy, inflammation, and cardiac fibrosis, closely resembling in vivo cardiac injury characteristics. Proteomic analysis revealed an enrichment of factors associated with ferroptosis in the injured LMS, suggesting a potential causative role. To test this hypothesis, we pharmacologically inhibited ferroptotic pathways using ferrostatin (Fer-1) in the cryoinjured rat LMS, resulting in attenuation of structural changes and repression of pro-fibrotic processes. Furthermore, LMS generated from failing human hearts were used as a model of chronic heart failure. In this model, Fer-1 treatment was observed to reduce the expression of ferroptotic genes, enhances contractile function and improves tissue viability. Blocking ferroptosis-associated pathways in human cardiac fibroblasts (HCFs) resulted in a downregulation of fibroblast activation genes, a decrease in fibroblast migration capacity, and a reduction in reactive oxygen species production. RNA sequencing analysis of Fer-1-treated human LMS implicated metallothioneins as a potential underlying mechanism for the inhibition of these pathways. This effect is possibly mediated through the replenishment of glutathione reserves. CONCLUSIONS: Our findings highlight the potential of targeting ferroptosis-related pathways and metallothioneins as a promising strategy for the treatment of heart disease.

The pleural gradient does not reflect the superimposed pressure in patients with class III obesity.

BACKGROUND: The superimposed pressure is the primary determinant of the pleural pressure gradient. Obesity is associated with elevated end-expiratory esophageal pressure, regardless of lung disease severity, and the superimposed pressure might not be the only determinant of the pleural pressure gradient. The study aims to measure partitioned respiratory mechanics and superimposed pressure in a cohort of patients admitted to the ICU with and without class III obesity (BMI ≥ 40 kg/m2), and to quantify the amount of thoracic adipose tissue and muscle through advanced imaging techniques. METHODS: This is a single-center observational study including ICU-admitted patients with acute respiratory failure who underwent a chest computed tomography scan within three days before/after esophageal manometry. The superimposed pressure was calculated from lung density and height of the largest axial lung slice. Automated deep-learning pipelines segmented lung parenchyma and quantified thoracic adipose tissue and skeletal muscle. RESULTS: N = 18 participants (50% female, age 60 [30-66] years), with 9 having BMI < 30 and 9  ≥ 40 kg/m2. Groups showed no significant differences in age, sex, clinical severity scores, or mortality. Patients with BMI ≥ 40 exhibited higher esophageal pressure (15.8 ± 2.6 vs. 8.3 ± 4.9 cmH2O, p = 0.001), higher pleural pressure gradient (11.1 ± 4.5 vs. 6.3 ± 4.9 cmH2O, p = 0.04), while superimposed pressure did not differ (6.8 ± 1.1 vs. 6.5 ± 1.5 cmH2O, p = 0.59). Subcutaneous and intrathoracic adipose tissue were significantly higher in subjects with BMI ≥ 40 and correlated positively with esophageal pressure and pleural pressure gradient (p < 0.05). Muscle areas did not differ between groups. CONCLUSIONS: In patients with class III obesity, the superimposed pressure does not approximate the pleural pressure gradient, which is higher than in patients with lower BMI. The quantity and distribution of subcutaneous and intrathoracic adiposity also contribute to increased pleural pressure gradients in individuals with BMI ≥ 40. This study introduces a novel physiological concept that provides a solid rationale for tailoring mechanical ventilation in patients with high BMI, where specific guidelines recommendations are lacking.

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia.

Significant evidence links obesity and schizophrenia (SZ), but the brain associations are still largely unclear. 48 people with SZ were divided into two subgroups: patients with lower waist circumference (SZ-LWC: n = 24) and patients with higher waist circumference (SZ-HWC: n = 24). Healthy controls (HC) were included for comparison (HC: n = 27). Using tract-based spatial statistics, we compared fractional anisotropy (FA) of the whole-brain white matter skeleton between these three groups (SZ-LWC, SZ-HWC, HC). Using Free Surfer, we compared whole-brain cortical thickness and the selected subcortical volumes between the three groups. FA of widespread white matter and the mean cortical thickness in the right temporal lobe and insular cortex were significantly lower in the SZ-HWC group than in the HC group. The FA of regional white matter was significantly lower in the SZ-LWC group than in the HC group. There were no significant differences in mean subcortical volumes between the groups. Additionally, the cognitive performances were worse in the SZ-HWC group, who had more severe triglycerides elevation. This study provides evidence for microstructural abnormalities of white matter, cortical thickness and neurocognitive deficits in SZ patients with excessive abdominal obesity.

The Liquid Metal Age: A Transition From Hg to Ga.

This review offers an illuminating journey through the historical evolution and modern-day applications of liquid metals, presenting a comprehensive view of their significance in diverse fields. Tracing the trajectory from mercury applications to contemporary innovations, the paper explores their pivotal role in industry and research. The analysis spans electrical switches, mechanical applications, electrodes, chemical synthesis, energy storage, thermal transport, electronics, and biomedicine. Each section examines the intricacies of liquid metal integration, elucidating their contributions to technological advancements and societal progress. Moreover, the review critically appraises the challenges and prospects inherent in liquid metal applications, addressing issues of recycling, corrosion management, device stability, economic feasibility, translational hurdles, and market dynamics. By delving into these complexities, the paper advances scholarly understanding and offers actionable insights for researchers, engineers, and policymakers. It aims to catalyze innovation, foster interdisciplinary collaboration, and promote liquid metal-enabled solutions for societal needs. Through its comprehensive analysis and forward-looking perspective, this review serves as a guide for navigating the landscape of liquid metal applications, bridging historical legacies with contemporary challenges, and highlighting the transformative potential of liquid metals in shaping future technologies.

Extracorporeal membrane oxygenation in cardiovascular medication poisoning. A German-wide retrospective study.

Medication poisoning, resulting from the ingestion of cardiotoxic drugs, presents a significant health issue. The mortality rate remains high for patients with myocardial dysfunction refractory to conventional treatments. Venoarterial Extracorporeal Membrane Oxygenation (V-A ECMO) provides temporary support, potentially enhancing patient outcomes. This study aims to assess the efficacy of V-A ECMO in treating cardiovascular failure induced by cardiovascular medication poisoning. We utilized inpatient data from all hospitalisations in Germany from 2007 to 2022 due to cardiovascular medication poisoning treated with V-A ECMO. Patient characteristics, comorbidities, complications and application of ECMO were described descriptively and analysed for statistical significance between survivors and non-survivors. Overall, 49 patients received V-A ECMO for cardiovascular medication poisoning, with a survival rate of 63.6%. The most ingested medications were calcium-channel blockers (38.8%) and beta-adrenoceptor antagonists (34.7%). Half of non-survivors received in-hospital CPR, compared to 12.9% of survivors. Early ECMO implantation (within 24 h of admission) was common (83.7%) but did not significantly impact survival rates. A substantial number of patients presented with multiple substances ingested. V-A ECMO represents a viable option for patients experiencing cardiac failure due to medication poisoning. A structured implementation of V-A ECMO for cardiovascular medication poisoning could lead to higher survival rates.

Characterizing Psychological Resources and Resilience in Patients With Bladder Cancer: Associations With Frailty and Quality of Life.

PURPOSE: Resilience, the ability to maintain or restore baseline function following a stressor, remains unexplored in patients with bladder cancer. Our objective was to demonstrate the feasibility of prospectively characterizing baseline resilience, related psychological resources and frailty in patients with bladder cancer and evaluate associations with quality of life and mental health outcomes over time. MATERIALS AND METHODS: We enrolled patients with bladder cancer (N = 67, September 2020-July 2021) into a prospective observational cohort study. At intake, subjects completed validated assessments of frailty domains and psychological resources (resilience, psychological capital, self-compassion, and thriving, collectively PsyResources). Validated quality of life surveys were completed at 2 weeks, 3- and 6-months post-treatment selection. Correlation matrices were constructed to quantify correlations between baseline PsyResources and frailty measures (reported with Spearman's correlation coefficient [ρ]). Associations between PsyResources and quality of life outcomes were evaluated with linear regression. RESULTS: Median age was 71 years (83.6% male) and 77.6% had muscle-invasive bladder cancer (cN+: 21%, M1: 7.6%). Baseline PsyResources were inversely correlated with the Geriatric Depression Scale (ρ = -0.50-0.65, P < .0001). Higher baseline PsyResources were associated with improved global symptoms and emotional function and decreased anxiety and depression over time (B: -0.17 to -2.5; P < .05). CONCLUSION: We present the first prospective characterization of baseline PsyResources in patients with bladder cancer. We observed positive correlations with improved mental health and quality of life outcomes over time. Ongoing work is exploring the relationship between resilience, frailty domains and their role in functional recovery following treatment. Future work is needed to understand associations between PsyResources and treatment tolerance, recovery trajectories, and oncologic outcomes.

Single-pulse ultrafast real-time simultaneous planar imaging of femtosecond laser-nanoparticle dynamics in flames.

The creation of carbonaceous nanoparticles and their dynamics in hydrocarbon flames are still debated in environmental, combustion, and material sciences. In this study, we introduce single-pulse femtosecond laser sheet-compressed ultrafast photography (fsLS-CUP), an ultrafast imaging technique specifically designed to shed light on and capture ultrafast dynamics stemming from interactions between femtosecond lasers and nanoparticles in flames in a single-shot. fsLS-CUP enables the first-time real-time billion frames-per-second (Gfps) simultaneous two-dimensional (2D) imaging of laser-induced fluorescence (LIF) and laser-induced heating (LIH) that are originated from polycyclic aromatic hydrocarbons (PAHs) and soot particles, respectively. Furthermore, fsLS-CUP provides the real-time spatiotemporal map of femtosecond laser-soot interaction as elastic light scattering (ELS) at an astonishing 250 Gfps. In contrast to existing single-shot ultrafast imaging approaches, which are limited to millions of frames per second only and require multiple laser pulses, our method employs only a single pulse and captures the entire dynamics of laser-induced signals at hundreds of Gfps. Using a single pulse does not change the optical properties of nanoparticles for a following pulse, thus allowing reliable spatiotemporal mapping. Moreover, we found that particle inception and growth are derived from precursors. In essence, as an imaging modality, fsLS-CUP offers ultrafast 2D diagnostics, contributing to the fundamental understanding of nanoparticle's inception and broader applications across different fields, such as material science and biomedical engineering.

Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial.

Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. We hypothesized that cryoablation may modify the immune microenvironment through direct modulation of the tumor, thereby generating an anti-tumor response in tumors refractory to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), subjects with unresectable melanoma progressing on ICI underwent cryoablation of an enlarging metastasis, and ICI was continued for a minimum of two additional cycles. The primary endpoints were safety, feasibility and tumor response in non-ablated lesions. From May 2018 through July 2020, 17 patients were treated on study. The study met its primary endpoints with the combination strategy found to be safe and feasible with an objective response rate of 23.5% and disease control rate of 41% (4 partial response, 3 stable disease). Our data support further study of this synergistic therapeutic approach.

Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline.

BACKGROUND: Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms. METHODS: Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project. RESULTS: The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the AGT (angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated. CONCLUSIONS: Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with AGT mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic AGT silencing for the treatment of hypertension).

In-Vitro Tooth Cleaning Efficacy and Filament End Rounding of Different Manual Children's Toothbrushes.

PURPOSE: This in-vitro study aimed to investigate the cleaning efficacy of 18 different manual children's toothbrushes applying horizontal, vertical, and rotational movements, as well as to evaluate the rounding of their filament ends. MATERIALS AND METHODS: Models equipped with artificial teeth (coated with titanium dioxide) were brushed using a brushing machine with clamped manual children's toothbrushes. The machine carried out horizontal, vertical, and rotational movements for 1 min with a constant contact pressure of 100 g. The percentage of the area of titanium dioxide removed from the buccal, mesial, distal and total surfaces of the artificial teeth corresponded to the cleaning efficacy. To assess the filament design, a scanning electron microscope was used to check the morphology of the filaments which was scored with Silverstone and Featherstone scale. SPSS 22 was used for data analysis. RESULTS: The rotational and the vertical movements achieved the best cleaning efficacy with all tested toothbrushes. The vast majority of the tested toothbrushes had their poorest cleaning efficacy in the horizontal movement. Only a small part of the children's toothbrushes (3 out of 18) had a correct and acceptable proportion of rounded bristle ends. CONCLUSIONS: Based on the present results, it could be concluded that the cleaning efficacy of different manual children's toothbrushes varied considerably. The best cleaning efficacy was almost always observed for rotational and vertical movements.

Subcutaneous and Visceral Adipose Tissue Reference Values From the Framingham Heart Study Thoracic and Abdominal CT.

BACKGROUND: Computed tomography (CT) captures the quantity, density, and distribution of subcutaneous and visceral (SAT and VAT) adipose tissue compartments. These metrics may change with age and sex. OBJECTIVE: The study aims to provide age-, sex-, and vertebral level-specific reference values for SAT on chest CT and for SAT and VAT on abdomen CT. MATERIALS AND METHODS: This secondary analysis of an observational study describes SAT and VAT measurements in participants of the Framingham Heart Study without known cancer diagnosis who underwent at least 1 of 2 CT examinations between 2002 and 2011. We used a previously validated machine learning-assisted pipeline and rigorous quality assurance to segment SAT at the fifth, eighth, and tenth thoracic vertebra (T5, T8, T10) and SAT and VAT at the third lumbar vertebra (L3). For each metric, we measured cross-sectional area (cm2) and mean attenuation (Hounsfield units [HU]) and calculated index (area/height2) (cm2/m2) and gauge (attenuation × index) (HU × cm2/m2). We summarized body composition metrics by age and sex and modeled sex-, age-, and vertebral level-specific reference curves. RESULTS: We included 14,898 single-level measurements from up to 4 vertebral levels of 3797 scans of 3730 Framingham Heart Study participants (1889 [51%] male with a mean [standard deviation] age of 55.6 ± 10.6 years; range, 38-81 years). The mean VAT index increased with age from 65 (cm2/m2) in males and 29 (cm2/m2) in females in the <45-year-old age group to 99 (cm2/m2) in males and 60 (cm2/m2) in females in >75-year-old age group. The increase of SAT with age was less pronounced, resulting in the VAT/SAT ratio increasing with age. A free R package and online interactive visual web interface allow access to reference values. CONCLUSIONS: This study establishes age-, sex-, and vertebral level-specific reference values for CT-assessed SAT at vertebral levels T5, T8, T10, and L3 and VAT at vertebral level L3.

A Multicenter Evaluation of Treatment-associated Changes in Body Composition in Men With Germ Cell Tumors of the Testis: Implications for Adverse Events and Complications.

OBJECTIVE: To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications. MATERIALS AND METHODS: This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3 + AEs and post-RPLND complications on multivariable logistic regression analyses. RESULTS: One hundred and eighty-two men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was -6% (P = <.0001), while VAI, SAI, and FMI increased by +13% (P = <.0001), +11% (P = <.0001), and +6% (P = <.0001), respectively. Seventy-nine patients (43%) experienced at least one grade 3 + AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3 + AEs (P = .047). One hundred and 3 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least 1 grade 3 + post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications. CONCLUSION: In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications.

Lung Needle Biopsy and Lung Ablation: Indications, Patient Management, and Postprocedure Imaging Findings.

The clinical role and use of percutaneous transthoracic needle biopsy (TTNB) and ablation of lung tumors are evolving. Here we discuss important considerations for referring providers, including current and emerging indications supported by guidelines, critical aspects of pre and postprocedure patient management, and expected postprocedure imaging findings.

High-Volume Liposuction in Lipedema Patients: Effects on Serum Vitamin D.

Background: Lipedema is a subcutaneous adipose tissue disorder characterized by increased pathological adipocytes mainly in the extremities. Vitamin D is stored in adipocytes, and serum levels inversely correlate with BMI. As adipocytes are removed during liposuction, lipedema patients might be prone to further substantial vitamin D loss while their levels are already decreased. Therefore, we examined the effect of liposuction on perioperative serum 25-hydroxyvitamin D levels. Methods: In patients undergoing lipedema liposuction, blood samples were obtained pre- and postoperatively. Statistical analyses were performed to correlate the volume of lipoaspirate, patients' BMI and number of sessions to vitamin D levels. Results: Overall, 213 patients were analyzed. Mean liposuction volume was 6615.33 ± 3884.25 mL, mean BMI was 32.18 ± 7.26 kg/m2. mean preoperative vitamin D levels were 30.1 ± 14.45 ng/mL (borderline deficient according to the endocrine society) and mean postoperative vitamin D levels were 21.91 ± 9.18 ng/mL (deficient). A significant decrease in serum vitamin D was seen in our patients (p < 0.001) of mean 7.83 ng/mL. The amount of vitamin D loss was not associated with BMI or aspiration volume in our patients (p > 0.05). Interestingly, vitamin D dynamics showed a steady drop regardless of volume aspirated or preoperative levels. Conclusions: Many lipedema patients have low vitamin D levels preoperatively. Liposuction significantly reduced these levels additionally, regardless of aspirated volume or BMI. However, vitamin D loss was constant and predictable; thus, patients at risk are easily identified. Overall, lipedema patients undergoing liposuction are prone to vitamin D deficiency, and the long-term effects in this population are currently unknown.

Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality.

BACKGROUND: The expansion of hematopoietic stem cells caused by acquired somatic mutations (clonal hematopoiesis [CH]) is a novel cardiovascular risk factor. The prognostic value of CH in patients with carotid atherosclerosis remains to be evaluated. OBJECTIVES: This study assessed the prognostic significance of CH in patients with atherosclerosis as detected by ultrasound of the carotid artery. METHODS: We applied deep sequencing of selected genomic regions within the genes DNMT3A, TET2, ASXL1, and JAK2 to screen for CH in 968 prospectively collected patients with asymptomatic carotid atherosclerosis evaluated by duplex sonography. RESULTS: We detected clonal markers at variant allele frequency ≥2% in 133 (13.7%) of 968 patients (median age 69.2 years), with increasing prevalence at advanced age. Multivariate analyses including age and established cardiovascular risk factors revealed overall presence of CH to be significantly associated with increased risk of cardiovascular death (HR: 1.50; 95% CI: 1.12-2.00; P = 0.007), reflected also at the single gene level. The effect of CH was more pronounced in older patients and independent of the patients' inflammatory status as measured by high-sensitivity C-reactive protein. Simultaneous assessment of CH and degree of carotid stenosis revealed combined effects on cardiovascular mortality, depicted by a superior risk for patients with >50% stenosis and concomitant CH (adjusted HR: 1.60; 95% CI: 1.08-2.38; P = 0.020). CONCLUSIONS: CH status in combination with the extent of carotid atherosclerosis jointly predict long-term mortality. Determination of CH can provide additional prognostic information in patients with asymptomatic carotid atherosclerosis.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

Signature of Altered Retinal Microstructures and Electrophysiology in Schizophrenia Spectrum Disorders Is Associated With Disease Severity and Polygenic Risk.

BACKGROUND: Optical coherence tomography and electroretinography studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSDs). However, it remains unclear which specific retinal layers are affected; how the retina, brain, and clinical symptomatology are connected; and how alterations of the visual system are related to genetic disease risk. METHODS: Optical coherence tomography, electroretinography, and brain magnetic resonance imaging were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSDs and 130 healthy control individuals. The sparse partial least squares algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with individual polygenic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual optical coherence tomography and electroretinography parameter. RESULTS: The sparse partial least squares analysis yielded a phenotype-eye-brain signature of SSDs in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSDs had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude. CONCLUSIONS: This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSDs that are associated with disease severity and individual polygenic burden.