Arteriolar Narrowing Research Articles

Retinal changes in preeclampsia

Background: The eye undergoes a series of physiological changes during pregnancy in response to metabolic and hormonal adaptation. Preeclampsia (PE) is the main cause of maternal morbidity and is associated with serious pregnancy-related complications. Characterized by hypertension and proteinuria, PE affects 2–8% of pregnancies globally. Previous studies have indicated that PE compromises retinal health. We examined the effects of PE on retinal structure and vasculature. Methods: We conducted a literature review by searching PubMed/MEDLINE, Embase, and Scopus using terms pertaining to PE and the retina. The review included articles published between January 1, 1990, and May 30, 2024. The articles were selected based on their relevance to the topic. The key findings are summarized to offer a comprehensive overview of current knowledge, highlight the pathophysiology and manifestations of PE-related retinal changes, and propose clinical implications, diagnostic clues, and management strategies. Results: PE is associated with visual disturbances caused by various retinal changes, including arteriolar narrowing, vasospasm, hemorrhages, exudates, serous retinal detachment, macular edema, retinal vein occlusion, and choroidal ischemia. These are mostly evident on fundus examination and frequently resolve postpartum. The underlying pathophysiology involves endothelial dysfunction, hypertension, inflammation, and coagulopathy. These retinal changes have immediate clinical implications and long-term risks, necessitating early detection, prompt multidisciplinary management, and close follow-up. Although most PE-associated retinal disturbances spontaneously resolve after the termination of pregnancy, one-third of patients are likely to experience long-lasting consequences Conclusions: Visual disturbances may precede and portend the onset of PE. Early detection and prompt management will mitigate fetal and maternal morbidity and mortality. Understanding the underlying pathophysiology of PE-related retinal manifestations is crucial for optimal management, because the majority of manifestations are reversible. Although retinal changes secondary to PE typically resolves postpartum, some studies demonstrated that women with PE may have a higher long-standing risk of ocular disorders. A multidisciplinary team approach involving obstetricians, ophthalmologists, and healthcare providers is essential for the immediate and long-term management of ocular consequences in pregnancy. Consequently, additional studies associated with robust methodologies are required to develop clinical guidelines.

Effect of Continuous Positive Airway Pressure Treatment on the Arteriole-to-Venule Ratio in Patients With Nonproliferative Diabetic Retinopathy and Obstructive Sleep Apnea: A Randomized Trial.

This study aimed to assess the effect of continuous positive airway pressure (CPAP) on the arteriolar-to-venular ratio (AVR) in patients with diabetic retinopathy (DR) and obstructive sleep apnea (OSA). A prospective, randomized, unblinded, and controlled clinical trial with parallel groups was performed. From a base of 138 patients, 83 were randomized to either CPAP or control. Nonstereoscopic 35º photographs were processed with Sirius software. The intention-to-treat analysis showed no differences in AVR, although the arteriolar diameter increased from baseline in the CPAP group. Per-protocol analysis showed a 12-month increase in AVR (P = 0.035) and arteriolar diameter (P = 0.033) in CPAP versus control group. The venular diameter showed a nonstatistically significant reduction. CPAP is a potentially novel treatment for individuals with DR and concomitant OSA, improving the retinopathy status, reversing the arteriolar narrowing, and therefore increasing the AVR, tending to reduce the venular diameter. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Retinal microvascular remodeling associates with adverse events in continuous-flow left ventricular assist device-supported patients

BackgroundContinuous-flow left ventricular assist device (cfLVAD) use is effective in supporting patients with end-stage heart failure (ESHF). Reduced flow pulsatility within the systemic circulation in cfLVAD-supported patients may lead to alterations within the microcirculation. Temporal changes in microvasculature in relation to adverse events in cfLVAD supported patients has not been studied. We aimed to profile changes within retinal microvasculature and its association with adverse events. MethodsRetinal photography was performed using Topcon TRC-NW8 non-mydriatic fundus camera in cfLVAD supported patients and ESHF control patients. Retinal measurements including arteriolar and venular caliber, fractal dimension, branching angle, and vessel tortuosity were evaluated using a validated semi-automated program. Demographic and adverse event data were documented. Results172 images were recorded from 48 patients (n=29 cfLVAD, n=19 ESHF, mean age 54.2 ± 11.9 years). There were significant trends in retinal arteriolar caliber (B = -0.53 µm, 95% CI: -0.96 – -0.10, p = 0.016) and retinal fractal dimension parameters (B = 0.014, 95% CI: 0.001 – 0.002, p = 0.016) in linear mixed model regressions. Amongst cfLVAD patients, there was a significant association between the incidence of gastrointestinal bleeding and stepwise increases in retinal arteriolar-venular caliber ratio (HR: 3.03, 95% CI: 2.06 – 4.45, p = 0.005), a measure of arteriolar narrowing. ConclusionsWe have observed for the first time that alterations in retinal microvasculature in cfLVAD-supported patients may be associated with gastrointestinal bleeding. While understanding these temporal changes may predict future adverse events in cfLVAD-supported patients, further multi-center studies are required to confirm the associations observed.

A Rare Case of Neuronal Ceroid Lipofuscinosis-Type 1 (NCL-1) with Vitamin D-Dependent Rickets-Type 1 (VDDR-1), Complex 1 Mitochondrial Deficiency, and Mixed Variant-Checkerboard and Phylloid Type of Pigmentary Mosaicism.

Introduction Neuronal ceroid lipofuscinosis-type 1 (NCL-1) is a neurodegenerative lysosomal storage disorder. Vitamin D-dependent rickets type 1 (VDDR-1) is a rare cause of refractory rickets. Here, we report an unusual association of NCL-1 with VDDR-1. Case A 3-year-old boy presented with a history of seizures from 45 days of life, delayed development, and loss of attained milestones at 20 months of age, along with progressive vision impairment since 1 year. Examination showed a failure to thrive, microcephaly, rachitic rosary, checkerboard and phylloid type of pigmentary mosaicism, fundus showed disc pallor with generalized narrowing of arterioles, bilateral retinitis pigmentosa, spasticity and dystonia, brisk reflexes, extensor plantar, and left choreoathetoid movements. Investigations showed hypocalcemia (7.8 mg/dL), normal phosphorus (3.9 mg/dL), elevated alkaline phosphatase (508.8 U/L), elevated parathyroid hormone (513.35 pg/mL), low 1,25-dihydroxy-vitamin D (9.93 pg/mL), and normal renal function. The child had metabolic acidosis, elevated ammonia (403.9 micromol/L), lactate (95 mg/dL, normal range 4.5-19.8 mg/dL), and creatine phosphokinase (432 U/L) level, and normal tandem mass spectroscopy. X-ray wrist showed healing vitamin deficiency rickets. Abnormal electroencephalogram was suggestive of low voltage activity. Magnetic resonance imaging brain showed gross cerebral and cerebellar atrophy. A muscle biopsy showed scattered atrophic fibers and several ultrastructural granular osmiophilic deposits and some mitochondrial aggregates of varying size were observed. Mitochondrial respiratory chain enzyme assay exhibited complex-1 deficiency (activity < 30%). Genetic analysis showed two pathogenic mutations: homozygous nonsynonymous variation c.674T > C in exon 7 of the PPT1 gene and a homozygous frameshift variation c.1178_1179delAA in exon 7 of CYP27B1 confirming the diagnosis of NCL-1 with VDDR-1. The child was treated with a low protein diet, levetiracetam, clonazepam, trihexyphenidyl, haloperidol, calcium supplement, calcitriol, and sodium benzoate; some improvement in clinical and biochemical parameters was noted on follow-up. Conclusion This is a novel association of NCL-1 with VDDR-1 associated with complex-1 mitochondrial deficiency which has previously not been reported in the literature.

#2909 Molecular mechanisms of early vascular damage in children with chronic renal failure

Abstract Background and Aims The risk of developing cardiovascular disease is exceedingly high in patients with chronic kidney disease (CKD), therapeutic options are limited. In order to develop specific therapies, a comprehensive molecular understanding of the underlying pathomechanisms is essential. Method Transcriptome and proteome analyses followed by pathway analyses (GO, GSEA) were performed from microdissected omental arterioles of 6 children with normal renal function and 8 children with CKD5 (median age 9.2 years), respective microproteomics were performed from laser microdissected endothelial layers. Key findings were validated independently by immunohistochemistry. Human endothelial umbilical vein cells (HUVEC) were exposed to plasma from children with normal renal function and children with CKD5. Tight junction (TJ) abundance was quantified in Transwells, ionic conductance by transendothelial resistance measurements and chromatin topology by Single Molecule Localization Microscopy (SMLM) followed by cluster/persistent homology analyses. The latter was compared to ion radiation induced chromatin re-organisation. Results Arteriolar lumen narrowing was already pronounced in children with CKD5 (lumen/vessel ratio; 0.58 vs. 0.76 in healthy individuals, p &amp;lt; 0.001), arteriolar intima and media thickness significantly increased. Biofunctions significantly regulated in CKD compared to controls at both transcriptome and proteome levels were immune response, chromatin organisation, actin cytoskeleton and TJ organization (FDR&amp;lt;0.25, p &amp;lt; 0.05). In independent cohorts of children with CKD5 (n = 20), the subendothelial space was infiltrated by CD68+ macrophages and endothelial histone2A abundance was reduced compared to children with normal renal function (n = 16). Repair foci at the places of DNA double strand breaks (DSB) visualized by yH2A.X were similar in both groups. HUVEC exposed to plasma from CKD5 children showed marked relaxation of H3K9 labeled heterochromatin compared to HUVEC exposed to plasma from children with normal renal function, and persistent homology analysis revealed CKD specific chromatin pattern. The CKD induced chromatin re-organisation differed from ion radiation induced DSB repair. Polarized endothelial cells exposed to plasma from CKD5 children had increased ion transport compared to cells exposed to plasma from healthy donors. Endothelial cell membrane abundance of the sealing TJ protein claudin-5 and of zonula occlundens-1, which links TJ to the actin cytoskeleton, was reduced by uremic plasma, TNFα and carbonyl stress. Co-incubation with histidine dipeptides and AlaGln ameliorated the loss of endothelial barrier function. Conclusion CKD5 leads to complex molecular pathomechanisms and functional alterations particularly including the immune response, chromatin re-organization and endothelial barrier dysfunction already in young children. Dipeptides represent potential therapeutic agents to protect the endothelial barrier function.

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

Retinal Vascular Imaging Application in Women’s Reproductive Health: Clinical Implications and Future Directions

Abstract Over the past two decades, population-based studies employing semiautomatic computer-assisted programs have uncovered associations between retinal microvascular features and various systemic conditions. As the recognition of retinal imaging in cardiometabolic health grows, there is increasing evidence supporting its application in women’s health, particularly during the reproductive age. This review aims to summarize the indications of retinal imaging in women’s health and intergenerational health, where suboptimal retinal imaging has been found to mirror pathological systemic changes, such as suboptimal hemodynamic circulation, inflammation, endothelial dysfunction, oxidative stress, and hypoxia in vivo. Findings from Singapore Growing Up in Singapore Towards Healthy Outcomes and Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohorts have reported serial changes in retinal conventional microvascular features (e.g., retinal arteriolar narrowing, retinal venular widening) and retinal geometric microvascular features (e.g., sparse fractal dimension, enlarged branching angle, and increased curvature tortuosity) during the preconception and antenatal phases. These morphological abnormalities were found to be related to female fertility, maternal antenatal health conditions, postnatal maternal cardiometabolic health, and intergenerational health in the fetus. Given the compelling evidence of the ability to detect microvascular changes through noninvasive methods at an early stage, retinal imaging holds the potential to facilitate timely interventions, mitigate the progression of complications, and prevent adverse pregnancy outcomes. Looking ahead, the convergence of artificial intelligence and advanced imaging techniques heralds a promising era in women’s health research and clinical practice.

Association between deep learning measured retinal vessel calibre and incident myocardial infarction in a retrospective cohort from the UK Biobank

BackgroundCardiovascular disease is a leading cause of global death. Prospective population-based studies have found that changes in retinal microvasculature are associated with the development of coronary artery disease. Recently, artificial...

THE OPTICAL COHERENCE TOMOGRAPHY (OCT) IN A PATIENT WITH RETINOPATHY-ASSOCIATED ECLAMPSIA: WHAT TO EXPECT?

Introduction : Eclampsia is a common pregnancy complication, that has been associated with retinopathy. Screening of retinopathy in preeclampsia/eclampsia is essential for early detection and management. Various imaging modalities are used to diagnose retinopathy. However, because of the higher-resolution imaging demand, optical coherence tomography (OCT) suggests a better option. The present study aimed to report the OCT findings of retinopathy-associated eclampsia.&#x0D; Case Illustration : A 24-year-old pregnant woman in 27th-week gestation with eclampsia presented the new onset of bilateral sudden diminution of vision. The vision in her right eye was limited to hand movement and that in her left eye was light perception only. Clinical examination revealed Siegrist streaks, Elschnig spots, and flame shape hemorrhages. OCT of both eyes demonstrated subretinal fluid, intraretinal fluid, thickening of the retinal layer, also inner retinal hyperreflectivity. Two months after the follow-up, there was an improvement in the OCT findings and also in the visual acuity.&#x0D; Discussion : An increase in macular thickness could be a characteristic feature in the OCT of retinopathy- associated eclampsia caused by retinal arteriolar narrowing due to systemic hypertension and ischemia. Previous studies have demonstrated subretinal/intraretinal fluid with or without serous retinal detachment in preeclampsia. Following our case, we report subretinal fluid, intraretinal fluid in the outer plexiform layer with retinal detachment and macular edema. The subretinal fluid and serous detachment were most likely caused by the changes in the fluid and ion-transport function of the retinal pigment epithelium (RPE).&#x0D; Conclusion : OCT can provide valuable information for diagnosis and follow-up retinopathy in preeclampsia/eclampsia.

Retinal vascular changes in persons with cerebral small vessel disease

The retinal and cerebral microvasculature share many morphological and physiological properties, Hence, it is thought that studying these retinal vessels will provide a direct measure to evaluate the vascular and neuronal status of the brain. In the present study, we aimed to study retinal vasculature by fundus examination in persons identified to have cerebral small vessel disease on MRI brain and an attempt to correlate the retinal vascular changes with the degree of MRI brain changes. A case control study was conducted in the department of Neurology, Jubilee Mission Medical College &amp; Research Institute. A total of 180 patients, included 90 patients for case group (Cerebral small vessel disease on MRI brain) and 90 patients for control group (no cerebral small vessel disease on MRI brain) reporting to the neurology department were included in the study. Cerebral small vessel disease was identified and classified/graded as per the modified Fazeka Scale. Ophthalmoscopic examination was done using fundus camera with the help of the ophthalmologist. Results were expressed in percentages and the data obtained was analysed using standard analytical techniques using SPSS software. Majority of cases and controls were in the age group of 61-70 years. Majority of the cases were males 55 (61.1%). Majority of the controls were females 51 (56.7%). 42 (46.7%) cases and 34 (37.8%) controls were hypertensives. Cases with CSVD had a statistically significant association with arteriolar narrowing, AV crossing changes and optic disc edema when compared to controls. Retinal vascular changes were associated with increased cerebral vascular events. These associations persist after accounting for confounding variables known to be disease causing in both circulations.

Evaluating the potential of retinal photography in chronic kidney disease detection: a review.

Chronic kidney disease (CKD) is a significant global health concern, emphasizing the necessity of early detection to facilitate prompt clinical intervention. Leveraging the unique ability of the retina to offer insights into systemic vascular health, it emerges as an interesting, non-invasive option for early CKD detection. Integrating this approach with existing invasive methods could provide a comprehensive understanding of patient health, enhancing diagnostic accuracy and treatment effectiveness. The purpose of this review is to critically assess the potential of retinal imaging to serve as a diagnostic tool for CKD detection based on retinal vascular changes. The review tracks the evolution from conventional manual evaluations to the latest state-of-the-art in deep learning. A comprehensive examination of the literature was carried out, using targeted database searches and a three-step methodology for article evaluation: identification, screening, and inclusion based on Prisma guidelines. Priority was given to unique and new research concerning the detection of CKD with retinal imaging. A total of 70 publications from 457 that were initially discovered satisfied our inclusion criteria and were thus subjected to analysis. Out of the 70 studies included, 35 investigated the correlation between diabetic retinopathy and CKD, 23 centered on the detection of CKD via retinal imaging, and four attempted to automate the detection through the combination of artificial intelligence and retinal imaging. Significant retinal features such as arteriolar narrowing, venular widening, specific retinopathy markers (like microaneurysms, hemorrhages, and exudates), and changes in arteriovenous ratio (AVR) have shown strong correlations with CKD progression. We also found that the combination of deep learning with retinal imaging for CKD detection could provide a very promising pathway. Accordingly, leveraging retinal imaging through this technique is expected to enhance the precision and prognostic capacity of the CKD detection system, offering a non-invasive diagnostic alternative that could transform patient care practices. In summary, retinal imaging holds high potential as a diagnostic tool for CKD because it is non-invasive, facilitates early detection through observable microvascular changes, offers predictive insights into renal health, and, when paired with deep learning algorithms, enhances the accuracy and effectiveness of CKD screening.

Morphological changes of the hepatobiliary system and salivary glands under the influence of stress

Stress can impact our bodies at the cellular level, causing changes to various organs and systems. Chronic stress can indirectly affect the hepatobiliary tract. Salivary gland dysfunction can be a manifestation of a large variety of systemic diseases or the consequence of local structural or functional pathologies. Stress can influence the oral microbiome, leading to changes in microbial diversity. Scientists study stress reactions, new resistance methods, and modern approaches to prevent and treat stress. &#x0D; The aim is to examine the morphological aspects and changes of the blood vessels in the liver and salivary glands of white rats in experiment using acute immobilization stress.&#x0D; Materials and methods. In total 22 white male rats were studied, divided into two groups. The first was kept as a control, the second was subjected to acute immobilization stress. The rats were immobilized by hanging them by the neck with a clamp for 6 hours. Animals were euthanized with a sodium thiopental solution. Samples of the liver and parotid gland were examined histologically using hematoxylin and eosin stain.&#x0D; Results. The livers of rats were studied after acute immobilization stress. Significant changes were observed in the liver blood vessels, including thrombosis and expansion of perisinusoidal spaces. Liver cells also showed changes such as karyopyknosis, colliquation necrosis, and hydropic dystrophy. The parotid salivary gland histologic examination showed swelling in the connective tissue, periductal regions, and perivascular spaces. In the acinar section, basophilia and swelling of serocytes were observed, along with dystrophic processes leading to remodeling of the acini and ducts. The narrowing of arterioles was observed, reflecting tension in the arterial system.&#x0D; Conclusions. Exposure to acute stress can cause changes in the liver and biliary tract, increasing the risk of various diseases, including those that affect the oral cavity.

RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

Retinopathy among women with hypertensive disorders of pregnancy attending hospitals in Mbarara city, south-western Uganda: a cross-sectional study

ObjectiveRetinopathy is one of the complications occurring among women with hypertensive disorders of pregnancy. We sought to determine the prevalence and factors associated with retinopathy among women with hypertensive disorders...

A deep learning system for retinal vessel calibre improves cardiovascular risk prediction in Asians with chronic kidney disease.

Cardiovascular disease (CVD) and mortality is elevated in chronic kidney disease (CKD). Retinal vessel calibre in retinal photographs is associated with cardiovascular risk and automated measurements may aid CVD risk prediction. Retrospective cohort study of 860 Chinese, Malay and Indian participants aged 40-80 years with CKD [estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2] who attended the baseline visit (2004-2011) of the Singapore Epidemiology of Eye Diseases Study. Retinal vessel calibre measurements were obtained by a deep learning system (DLS). Incident CVD [non-fatal acute myocardial infarction (MI) and stroke, and death due to MI, stroke and other CVD] in those who were free of CVD at baseline was ascertained until 31 December 2019. Risk factors (established, kidney, and retinal features) were examined using Cox proportional hazards regression models. Model performance was assessed for discrimination, fit, and net reclassification improvement (NRI). Incident CVD occurred in 289 (33.6%) over mean follow-up of 9.3 (4.3)years. After adjusting for established cardiovascular risk factors, eGFR [adjusted HR 0.98 (95% CI: 0.97-0.99)] and retinal arteriolar narrowing [adjusted HR 1.40 (95% CI: 1.17-1.68)], but not venular dilation, were independent predictors for CVD in CKD. The addition of eGFR and retinal features to established cardiovascular risk factors improved model discrimination with significantly better fit and better risk prediction according to the low (<15%), intermediate (15-29.9%), and high (30% or more) risk categories (NRI 5.8%), and with higher risk thresholds (NRI 12.7%). Retinal vessel calibre measurements by DLS were significantly associated with incident CVD independent of established CVD risk factors. Addition of kidney function and retinal vessel calibre parameters may improve CVD risk prediction among Asians with CKD.

Food intake in South African children and retinal microvascular health: The ExAMIN Youth SA study

Background and aimsRetinal arteriolar narrowing and venular widening are associated with increased cardiovascular risk, even at young ages. Whether diet contributes to early microvascular changes in children is not widely explored. We explored the associations of frequency of healthy and unhealthy food group intake with retinal vessel calibers in black and white children. Methods and resultsThis study included school-aged (5–9 years) black (N = 433, 7.46 ± 0.98 years), and white (N = 403, 7.43 ± 0.82 years) children. Anthropometric and blood pressure measurements were taken, along with retinal vessel calibers (central retinal arteriolar (CRAE) and venular (CRVE) equivalents). Frequencies of food group intake were assessed using a food-frequency questionnaire. A factor analysis was performed to describe food group patters. Independent associations between retinal vessel calibers and frequencies of food group intake and food group patters were explored. In black children, cookies, cakes, and biscuits were associated with narrower arterioles (p < 0.05). In white children, cold sweetened beverages were associated with narrower arterioles (p = 0.02), whereas salty snacks were associated with narrower arterioles (p = 0.01) and wider venules (p < 0.05). Fruits were positively associated with CRAE (p = 0.03) in white children only. ConclusionA higher frequency of unhealthy food group consumption was associated with retinal arteriolar narrowing and venular widening in both black and white children. However, fruit intake was shown beneficial for retinal microvascular health in white children only. Our findings may highlight the importance of promoting healthy eating patterns from early childhood which may reduce the risk of premature cardiovascular disease development.

Preconception maternal retinal arteriolar narrowing and fetal growth throughout pregnancy: A prospective cohort study.

To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth. A hospital-based, prospective preconception cohort including 369 women with a singleton live birth. We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit. We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11-13, 18-21, 24-28, and 32-34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH-21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24-28 weeks and 32-34 weeks of gestation, after full adjustment. Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (-0.34; 95% CI -0.66 to -0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (-0.41; 95% CI -0.90 to -0.001) and fetal FL (-0.55; 95% CI -1.00 to -0.10) between 24-28 weeks and 32-34 weeks of gestation, respectively. Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.

#5664 PERITONEAL DIFFUSE PODOPLANIN EXPRESSION IS ASSOCIATED WITH SEVERE ARTERIOLOPATHY IN CHILDREN ON PERITONEAL DIALYSIS

Abstract Background and Aims Podoplanin is a transmembrane glycoprotein binding chemokines and modulating inflammatory reactions. In healthy peritoneum, it is expressed in mesothelial cells and in lymphatic endothelium, expression beyond these structures (diffuse podoplanin staining, DPS) has been observed in adult patients with encapsulating peritoneal sclerosis (EPS). Method Parietal peritoneal tissues from 71 children on PD fluids with low glucose degradation product (GDP) content underwent digital histomorphometry. DPS and pathomechanisms of peritoneal membrane transformation and vasculopathy were hierarchically clustered. A panel of 13 peritoneal cell markers was selected and tissue sections were stained with metal conjugated antibodies and acquired using imaging mass cytometry (IMC; Hyperion Imaging System®). After single-cell segmentation, spillover correction, and normalization, cell types were identified using manual gating to train a random forest classifier for final cell type identifications using published workflows. Single-cell analysis was used to characterize peritoneal cells with positive podoplanin signals. Results DPS was present in 22% of the PD patients, all devoid of any clinical, radiological or histological feature of EPS. DPS positive patients were younger, had higher dialytic glucose exposure (median 103 vs. 154 g/m²/day, p = 0.002), and lower peritoneal arteriolar lumen to vessel (L/V) ratio, i.e. exhibited more arteriolar lumen narrowing. PD duration [median 20 (14.5, 48) months] and peritonitis incidence were similar as in non-DPS patients. In multivariable analysis, glucose exposure, PD duration, epithelial-to-mesenchymal transformed (EMT) cells and lower patient body surface area (BSA) independently predicted the presence of DPS. DPS and lower mesothelial surface coverage predicted lower arteriolar L/V ratio. In subgroups matched for BSA, PD duration and dialytic glucose exposure, DPS patients had a lower L/V ratio, (0.44 ± 0.13 vs. 0.31 ± 0.18, p = 0.003) and higher submesothelial CD45 leucocyte, CD68 macrophage and EMT cell count. Submesothelial lipopolysaccharide and hyaluronic acid receptor CD44 were increased in DPS positive patients, hyaluronan synthase 1 and 2 were similar. Among DPS positive patients, DPS intensity grade was higher in those with history of bacterial or fungal peritonitis (7 out of 15). Two patients had three and four peritonitis episodes respectively, their DPS pattern did not differ from patients with history of only one peritonitis episode. Hierarchical clustering demonstrated highest similarity of DPS positive areas with CD68 positive areas. In IMC analysis of DPS positive areas, highest podoplanin signals were derived from M2 classified macrophages (CD68+CD163+) and fibroblastic cells [αSMA positive/non-endothelial/non-macrophage (αSMA+PROX1-CD31-CD68-CD163-)], signals derived from M1 classified macrophages (CD68+CD163-) were lowest. Conclusion Peritoneal DPS in pediatric patients on low-GDP PD is associated with lower BSA, higher dialytic glucose exposure, history of infectious peritonitis and peritoneal inflammatory and EMT cell invasion, and predicts obliterating peritoneal vasculopathy. We identified M2 macrophages as major source of extra-lymphatic peritoneal podoplanin accumulation, suggesting their role in severe peritoneal transformation.

URINARY PROTEOMIC SIGNATURE OF THE RETINAL MICROVASCULATURE

Objective: The retinal vasculature provides a window into the body's microcirculation. Variations in retinal vessel diameters have been associated with adverse cardiovascular outcomes, such as stroke and coronary heart disease. As the pathogenesis of retinal microvascular diameter changes remain poorly understood, this study aimed to provide novel insights by characterizing the urinary proteomic signature of the retinal microvasculature. Design and method: The central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriole-to venule-ratio (AVR) were measured from digitized retinal photographs of 562 randomly recruited Flemish participants (mean age, 48.9 years; 50.9% women). The urinary proteome was analyzed using capillary electrophoresis coupled with mass spectrometry. Multivariable linear regression analysis identified significant urinary peptides with adjustment for age, sex, body mass index, smoking, hypertension, plasma glucose, total and HDL cholesterol, eGFR, and history of cardiovascular disease. Reactome pathway enrichment analysis was performed to interpret the proteomic signature. Results: Table 1 shows participant characteristics. Of the 359 peptides analyzed, 19 were significantly associated with CRAE after adjusting for potential confounders and multiple testing (Table 2). In the proteomic profile, 14 peptides (74%) were fragments of collagen I, III, and XI proteins, while the remaining peptides were fragments of the fibrinogen alpha chain (11%), xylosyltransferase 1 (5%), S100 calcium-binding protein A9 (5%), and hemoglobin subunit alpha (5%) proteins. Pathway analysis showed that these proteins were predominantly involved in endothelial cell proliferation and migration, collagen formation and degradation, and cell-extracellular matrix interactions (Figure 1). No peptides were significantly associated with CRVE and AVR following adjustment. Conclusions: This study revealed a novel urinary proteomic signature as a potential biomarker of retinal arteriolar narrowing. The signature suggests fibrosis and neovascularization may be involved in retinal microvascular diameter changes. Further investigation may help elucidate the pathophysiologic mechanisms underlying the relationship between microvascular and macrovascular disease.

Commentary: Clinical profile, demographic distribution, and outcomes of ocular siderosis: Electronic medical record-driven big data analytics from an eye care network in India.

Commentary: Clinical profile, demographic distribution, and outcomes of ocular siderosis: Electronic medical record-driven big data analytics from an eye care network in India.