The temporal relationship between body composition and cardiometabolic profiles in an HIV-infected (on antiretroviral therapy) versus HIV-free Western Cape study population.

Cardiovascular risk is a health concern in people living with HIV/AIDS (PLWH). This longitudinal study (baseline vs 36 months) aimed to investigate the relationship between body composition and markers of cardiovascular risk in a South African study population [HIV free, n = 22 vs HIV positive on antiretroviral therapy (HIV+ART), n = 73)]. Health questionnaires, anthropometric measurements, biochemical analyses and flow-mediated dilation were performed. Linear mixed-model statistical analyses were applied. The HIV+ART vs the HIV-free groups were independently associated with body mass index (BMI) [-4.92 (-7.99 to -1.84), p = 0.002] and waist circumference [-10.5 (-17.2 to -3.77), p = 0.003]. ART duration was associated with BMI [2.60 (0.57-4.62), p = 0.013], waist circumference [3.83 (0.03-7.63), p = 0.048] and high-density lipoprotein cholesterol [20.18 (2.37-41.09), p = 0.025]. The data showed that intricate relationships existed in this study population between HIV, ART, body composition and cardiometabolic variables. There is a need for more research investigating cardiovascular risk in PLWH, particularly in the context of changes in body composition measures.

Retinal venular vessel diameters are smaller during ten days of bed rest.

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m-2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

A pilot study: Exploring the influence of COVID-19 on cardiovascular physiology and retinal microcirculation.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the cardiovascular system. The current study investigated changes in heart rate (HR), blood pressure (BP), pulse wave velocity (PWV), and microcirculation in patients recovering from Coronavirus disease 2019 (COVID-19) infection. METHODOLOGY: Out of 43 initially contacted COVID-19 patients, 35 (30 males, 5 females; age: 60 ± 10 years; and body mass index (BMI): 31.8 ± 4.9) participated in this study. Participants were seen on two occasions after hospital discharge; the baseline measurements were collected, either on the day of hospital discharge if a negative PCR test was obtained, or on the 10th day after hospitalization if the PCR test was positive. The second measurements were done 60 days after hospitalization. The vascular measurements were performed using the VICORDER® device and a retinal blood vessel image analysis. RESULTS: A significant increase in systolic BP (SBP) (from 142 mmHg, SD: 15, to 150 mmHg, SD: 19, p = 0.041), reduction in HR (from 76 bpm, SD: 15, to 69 bpm, SD: 11, p = 0.001), and narrower central retinal vein equivalent (CRVE) (from 240.94 µm, SD: 16.05, to 198.05 µm, SD: 17.36, p = 0.013) were found. Furthermore, the trends of increasing PWV (from 11 m/s, SD: 3, to 12 m/s, SD: 3, p = 0.095) and decreasing CRAE (from 138.87 µm, SD: 12.19, to 136.77 µm, SD: 13.19, p = 0.068) were recorded. CONCLUSION: The present study investigated cardiovascular changes following COVID-19 infection at two-time points after hospital discharge (baseline measurements and 60 days post-hospitalization). Significant changes were found in systolic blood pressure, heart rate, and microvasculature indicating that vascular adaptations may be ongoing even weeks after hospitalization from COVID-19 infection. Future studies could involve conducting additional interim assessments during the active infection and post-infection periods.

A generalizable deep learning regression model for automated glaucoma screening from fundus images.

A plethora of classification models for the detection of glaucoma from fundus images have been proposed in recent years. Often trained with data from a single glaucoma clinic, they report impressive performance on internal test sets, but tend to struggle in generalizing to external sets. This performance drop can be attributed to data shifts in glaucoma prevalence, fundus camera, and the definition of glaucoma ground truth. In this study, we confirm that a previously described regression network for glaucoma referral (G-RISK) obtains excellent results in a variety of challenging settings. Thirteen different data sources of labeled fundus images were utilized. The data sources include two large population cohorts (Australian Blue Mountains Eye Study, BMES and German Gutenberg Health Study, GHS) and 11 publicly available datasets (AIROGS, ORIGA, REFUGE1, LAG, ODIR, REFUGE2, GAMMA, RIM-ONEr3, RIM-ONE DL, ACRIMA, PAPILA). To minimize data shifts in input data, a standardized image processing strategy was developed to obtain 30° disc-centered images from the original data. A total of 149,455 images were included for model testing. Area under the receiver operating characteristic curve (AUC) for BMES and GHS population cohorts were at 0.976 [95% CI: 0.967-0.986] and 0.984 [95% CI: 0.980-0.991] on participant level, respectively. At a fixed specificity of 95%, sensitivities were at 87.3% and 90.3%, respectively, surpassing the minimum criteria of 85% sensitivity recommended by Prevent Blindness America. AUC values on the eleven publicly available data sets ranged from 0.854 to 0.988. These results confirm the excellent generalizability of a glaucoma risk regression model trained with homogeneous data from a single tertiary referral center. Further validation using prospective cohort studies is warranted.

Exposure to endocrine disrupters and cardiometabolic health effects in preschool children: Urinary parabens are associated with wider retinal venular vessels.

BACKGROUND AND AIM: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life. METHODS: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. RESULTS: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) µg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (ß = 1.23, p = 0.039) and PrP with the retinal tortuosity index (x103)(ß = 1.75, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (ß = -0.067, p = 0.015 and ß = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (ß = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (ß = 0.10, p = 0.060). CONCLUSIONS: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature.

Vascular Responses following Light Therapy: A Pilot Study with Healthy Volunteers.

(1) Background: Studies have reported the effectiveness of light therapy in various medical conditions. Our pilot study aimed to assess the effect of Maharishi light therapy (MLT) on physiological parameters, such as the heart rate (HR), HR variability (HRV), blood pressure (BP), BP variability (BPV), and the retinal microvasculature of healthy participants; (2) Methodology: Thirty (14 males and 16 females) healthy, non-smoking participants between 23 and 71 years old (46 ± 18 years) were included in this randomized crossover study. Each participant was tested with a placebo (using LED light) and gem lights, 24 h apart. Hemodynamic parameters were recorded during the session, and 24 h heart rate and BP levels were assessed via mobile devices. Retinal vascular responses were captured with fundus images and the subsequent analysis of retinal vessel widths. A linear model, using repeated measures ANOVA, was used to compare the responses across the sexes and to assess the effect of the MLT; (3) Results: Changes in the central retinal artery equivalent (CRAE) (p < 0.001) and central retinal vein equivalent (CRVE) (p = 0.002) parameters were observed. CRAE and CRVE decreased under MLT and increased under the placebo condition from before to after. However, the baseline values of the participants already differed significantly before the application of any therapy, and the variation in the retinal vessel diameters was already large in the baseline measurements. This suggests that the observed effect results may only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. Furthermore, no significant effects were observed in any other investigated parameters; (4) Conclusion: Our study with healthy participants finds significant changes in retinal parameters, but the biological variation in the baseline measurements was large to begin with. This suggests that the observed effect results only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. However, in the future, larger studies in which MLT is applied for longer periods and/or in patients with different diseases could discover the physiological impacts of this type of therapy.

Endothelial function in patients with COPD: an updated systematic review of studies using flow-mediated dilatation.

INTRODUCTION: Cardiovascular disease is a significant cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be involved in cardiovascular disease pathogenesis, and multiple studies report endothelial dysfunction in COPD. This article summarized the current knowledge on endothelial function in COPD patients. AREAS COVERED: Databases were screened until November 2022 for studies using ultrasound-based flow-mediated dilation in patients with stable COPD. Pooled effect sizes were calculated using random effects model. Meta-regression analyses assessed the effects of demographic and clinical variables. EXPERT OPINION: 34 studies were identified (1365 COPD patients; 617 controls). Pooled analysis demonstrated an impaired endothelial-dependent (-2.33%; 95%CI -3.30/-1.35; p < 0.001) and endothelial-independent dilation (-3.11%; 95%CI -5.14/-1.08; p = 0.003) in COPD patients when compared to non-COPD controls. Meta-regression identified that higher age, worse severity of airflow obstruction, and current smoking were significantly associated with impaired endothelial function. Studies evaluating the effects of pharmacological and non-pharmacological interventions on endothelial function in COPD patients demonstrated conflicting results.

Artificial Intelligence Software for Diabetic Eye Screening: Diagnostic Performance and Impact of Stratification.

AIM: To evaluate the MONA.health artificial intelligence screening software for detecting referable diabetic retinopathy (DR) and diabetic macular edema (DME), including subgroup analysis. METHODS: The algorithm's threshold value was fixed at the 90% sensitivity operating point on the receiver operating curve to perform the disease classification. Diagnostic performance was appraised on a private test set and publicly available datasets. Stratification analysis was executed on the private test set considering age, ethnicity, sex, insulin dependency, year of examination, camera type, image quality, and dilatation status. RESULTS: The software displayed an area under the curve (AUC) of 97.28% for DR and 98.08% for DME on the private test set. The specificity and sensitivity for combined DR and DME predictions were 94.24 and 90.91%, respectively. The AUC ranged from 96.91 to 97.99% on the publicly available datasets for DR. AUC values were above 95% in all subgroups, with lower predictive values found for individuals above the age of 65 (82.51% sensitivity) and Caucasians (84.03% sensitivity). CONCLUSION: We report good overall performance of the MONA.health screening software for DR and DME. The software performance remains stable with no significant deterioration of the deep learning models in any studied strata.

Pointwise Visual Field Estimation From Optical Coherence Tomography in Glaucoma Using Deep Learning.

Purpose: Standard automated perimetry is the gold standard to monitor visual field (VF) loss in glaucoma management, but it is prone to intrasubject variability. We trained and validated a customized deep learning (DL) regression model with Xception backbone that estimates pointwise and overall VF sensitivity from unsegmented optical coherence tomography (OCT) scans. Methods: DL regression models have been trained with four imaging modalities (circumpapillary OCT at 3.5 mm, 4.1 mm, and 4.7 mm diameter) and scanning laser ophthalmoscopy en face images to estimate mean deviation (MD) and 52 threshold values. This retrospective study used data from patients who underwent a complete glaucoma examination, including a reliable Humphrey Field Analyzer (HFA) 24-2 SITA Standard (SS) VF exam and a SPECTRALIS OCT. Results: For MD estimation, weighted prediction averaging of all four individuals yielded a mean absolute error (MAE) of 2.89 dB (2.50-3.30) on 186 test images, reducing the baseline by 54% (MAEdecr%). For 52 VF threshold values' estimation, the weighted ensemble model resulted in an MAE of 4.82 dB (4.45-5.22), representing an MAEdecr% of 38% from baseline when predicting the pointwise mean value. DL managed to explain 75% and 58% of the variance (R2) in MD and pointwise sensitivity estimation, respectively. Conclusions: Deep learning can estimate global and pointwise VF sensitivities that fall almost entirely within the 90% test-retest confidence intervals of the 24-2 SS test. Translational Relevance: Fast and consistent VF prediction from unsegmented OCT scans could become a solution for visual function estimation in patients unable to perform reliable VF exams.

Analysis of Retinal Blood Vessel Diameters in Pregnant Women Practicing Yoga: A Feasibility Study.

Studies have shown that practicing yoga during pregnancy beneficially affects maternal and neonatal outcomes. The objective of this study was to determine the effect of prenatal yoga on the microvascular circulatory system via non-invasive measurements of retinal blood vessels. We included 29 women who practiced prenatal yoga in the study. There were no statistically significant differences in arteriolar and venular diameters pre- vs. post-90 min yoga practice (150.5 ± 11.4 µm pre- vs. 151.2 ± 10.2 µm post-yoga; p = 0.53 for arteriolar and 221.8 ± 16.1 µm pre- vs. 223.2 ± 15.7 µm post-yoga; p = 0.51 for venular diameters). The current study demonstrated the feasibility of the setup. More extensive studies are needed to determine the potential microvascular effects of practicing yoga throughout pregnancy.

Cardiovascular Profile of South African Adults with Low-Level Viremia during Antiretroviral Therapy.

Chronic inflammation is an HIV infection feature, contributing to elevated risk of cardiovascular disease among people with HIV, which can be induced by viral replication. A proportion of antiretroviral therapy (ART) recipients fail to achieve viral suppression, despite not meeting criteria for treatment failure, so-called low-level viremia (LLV). We investigated the relationship between LLV and an array of cardiovascular measures and biomarkers. South Africans with LLV (viral load = 50−999 copies/mL) and virological suppression (viral load <50 copies/mL) were selected from the EndoAfrica study (all receiving efavirenz-based ART) for cross-sectional comparison of vascular structure and function measures, as well as 21 plasma biomarkers related to cardiovascular risk and inflammation. Associations were investigated with univariate, multivariate, and binomial logistic regression analyses (having outcome measures above (cases) or below (controls) the 75th percentile). Among 208 participants, 95 (46%) had LLV, and 113 (54%) had viral suppression. The median age was 44 years, 73% were women, and the median ART duration was 4.5 years. Cardiovascular measures and biomarker levels were similar between these two categories. Cardiovascular function and structure measures were not associated with viremia status and having LLV did not increase the odds of having outcome measures above the 75th percentile. In this study among South African ART recipients, LLV did not associate with cardiovascular risk.

Retinal vessel multifractals predict pial collateral status in patients with acute ischemic stroke.

OBJECTIVES: Pial collateral blood flow is a major determinant of the outcomes of acute ischemic stroke. This study was undertaken to determine whether retinal vessel metrics can predict the pial collateral status and stroke outcomes in patients. METHODS: Thirty-five patients with acute stroke secondary to middle cerebral artery (MCA) occlusion underwent grading of their pial collateral status from computed tomography angiography and retinal vessel analysis from retinal fundus images. RESULTS: The NIHSS (14.7 ± 5.5 vs 10.1 ± 5.8, p = 0.026) and mRS (2.9 ± 1.6 vs 1.9 ± 1.3, p = 0.048) scores were higher at admission in patients with poor compared to good pial collaterals. Retinal vessel multifractals: D0 (1.673±0.028vs1.652±0.025, p = 0.028), D1 (1.609±0.027vs1.590±0.025, p = 0.044) and f(α)max (1.674±0.027vs1.652±0.024, p = 0.019) were higher in patients with poor compared to good pial collaterals. Furthermore, support vector machine learning achieved a fair sensitivity (0.743) and specificity (0.707) for differentiating patients with poor from good pial collaterals. Age (p = 0.702), BMI (p = 0.422), total cholesterol (p = 0.842), triglycerides (p = 0.673), LDL (p = 0.952), HDL (p = 0.366), systolic blood pressure (p = 0.727), HbA1c (p = 0.261) and standard retinal metrics including CRAE (p = 0.084), CRVE (p = 0.946), AVR (p = 0.148), tortuosity index (p = 0.790), monofractal Df (p = 0.576), lacunarity (p = 0.531), curve asymmetry (p = 0.679) and singularity length (p = 0.937) did not differ between patients with poor compared to good pial collaterals. CONCLUSIONS: This is the first translational study to show increased retinal vessel multifractal dimensions in patients with acute ischemic stroke and poor pial collaterals. A retinal vessel classifier was developed to differentiate between patients with poor and good pial collaterals and may allow rapid non-invasive identification of patients with poor pial collaterals.

Comparison of endothelial function and cardiometabolic profiles of people living with HIV in two South African regions: the EndoAfrica study.

BACKGROUND: People living with HIV (PLWH) are at risk for cardiovascular disease, but regional differences have not been studied in South Africa. We compared endothelial function and cardiometabolic markers in PLWH and HIV-free controls from two distinct South African regions. METHODS: We measured flow-mediated dilation (FMD), cardiometabolic, immunological and viral markers in age- and gender-matched PLWH on antiretroviral therapy (n = 100/group) and HIV-free participants (n = 50/group) in samples from cohort studies in the North West and Western Cape provinces. RESULTS: Endothelial function and cardiometabolic profiles were not worse in PLWH than in HIV-free individuals, and %FMD was not associated with cardiometabolic, viral or immunological markers. PLWH from the North West region had lower %FMD but overall better metabolic profiles. CONCLUSIONS: Ethnic, cultural and socio-economic differences need further investigation to understand the possible protective role of antiretroviral treatment on the vasculature and to direct region-specific HIV and AIDS guidelines in South Africa.

Age-related changes in the fractal dimension of the retinal microvasculature, effects of cardiovascular risk factors and smoking behaviour.

PURPOSE: This cross-sectional study investigates the association between retinal vessel complexity and age and studies the effects of cardiovascular health determinants. METHODS: Retinal vessel complexity was assessed by calculating the box-counting fractal dimension (Df ) from digital fundus photographs of 850 subjects (3-97 years). All photographs were labelled as 'non-pathological' by the treating ophthalmologist. RESULTS: Statistical models showed a significantly decreasing relationship between age and Df (linear: R-squared = 0.1897, p < 0.0001; quadratic: R-squared = 0.2343, p < 0.0001; cubic: R-squared = 0.2721, p < 0.0001), with the cubic regression model offering the best compromise between accuracy and model simplicity. Multivariate cubic regression showed that age, spherical equivalent and smoking behaviour have an effect (p < 0.0001) on Df . A significantly increasing effect of the number of pack-years on Df was observed (effect: 0.0004, p = 0.0017), as well as a significantly decreasing effect of years since tobacco abstinence (effect: -0.0149, p < 0.0001). CONCLUSION: We propose using a cubic trend with age, refractive error and smoking behaviour when interpreting retinal vessel complexity.

Analysis of retinal blood vessel diameters in patients with COPD undergoing a pulmonary rehabilitation program.

BACKGROUND: Regular exercise positively affects cardiovascular physiology, translating into the adequate capacity of microvascular blood vessels to dilate in response to acute bouts of exercise. However, this remains unstudied in patients with chronic obstructive pulmonary disease (COPD), who often suffer from cardiovascular comorbidity. Therefore, we studied acute changes in retinal blood vessel diameters in response to high-intensity exercise in patients with COPD. The effect of an exercise-based 8-week pulmonary rehabilitation (PR) program was evaluated. We consider changes in these retinal metrics as an indicator of microvascular reactivity. METHODS: Demographics and clinical characteristics of 41 patients were collected at the start and end of the PR program. Patients performed a high-intensity exercise test on a cycle ergometer at the start and end of the PR program, during which we collected retinal images. Fundus images were taken immediately before and 0, 5, 10, 15, and 30 min after the ergometer test. Widths of retinal blood vessels, represented as Central Retinal Arteriolar and Venular Equivalents (CRAE and CRVE), were calculated. RESULTS: Thirty patients with COPD completed the study protocol (57% males; mean age: 64 ± 7 years; mean FEV1: 45 ± 17%pred). We did not observe a change in retinal vessel widths following the ergometer test at the start of the PR program. This null result remained at the end of the 8-week PR program. Our observations did not alter when considering responders and non-responders to PR. CONCLUSION: Retinal blood vessel diameters of patients with COPD did not change following an exercise test on an ergometer. The exercise-based PR program of eight weeks did not counteract the blunted retinal microvascular response.

Deep learning on fundus images detects glaucoma beyond the optic disc.

Although unprecedented sensitivity and specificity values are reported, recent glaucoma detection deep learning models lack in decision transparency. Here, we propose a methodology that advances explainable deep learning in the field of glaucoma detection and vertical cup-disc ratio (VCDR), an important risk factor. We trained and evaluated deep learning models using fundus images that underwent a certain cropping policy. We defined the crop radius as a percentage of image size, centered on the optic nerve head (ONH), with an equidistant spaced range from 10-60% (ONH crop policy). The inverse of the cropping mask was also applied (periphery crop policy). Trained models using original images resulted in an area under the curve (AUC) of 0.94 [95% CI 0.92-0.96] for glaucoma detection, and a coefficient of determination (R2) equal to 77% [95% CI 0.77-0.79] for VCDR estimation. Models that were trained on images with absence of the ONH are still able to obtain significant performance (0.88 [95% CI 0.85-0.90] AUC for glaucoma detection and 37% [95% CI 0.35-0.40] R2 score for VCDR estimation in the most extreme setup of 60% ONH crop). Our findings provide the first irrefutable evidence that deep learning can detect glaucoma from fundus image regions outside the ONH.

HIV and Antiretroviral Therapy Are Independently Associated with Cardiometabolic Variables and Cardiac Electrical Activity in Adults from the Western Cape Region of South Africa.

Cardiovascular-related complications are on the rise in people with HIV/AIDS (PWH); however, the relationship among HIV and antiretroviral therapy (ART)-related parameters, cardiovascular risk, and cardiac electrical activity in PWH remain poorly studied, especially in sub-Saharan African populations. We investigated whether HIV and ART are associated with cardiometabolic and cardiac electrical activity in PWH from Worcester in the Western Cape Province, South Africa. This was a cross-sectional study with HIV-negative (HIV-, n = 24) and HIV-positive on ART (HIV+/ART+, n = 63) participants. We obtained demographic, lifestyle, and medical history data and performed anthropometric, clinical assessments, and blood/urine biochemistry. We performed multiple stepwise linear regression analyses to determine independent associations among HIV, ART, cardiometabolic, and electrocardiographic (ECG) variables. HIV+/ART+ independently associated with a lower body mass index (p = 0.004), elevated gamma-glutamyl transferase levels (ß: 0.333 (0.130-0.573); p = 0.002), and elevated alanine aminotransferase levels (ß: 0.427 (0.224-0.629); p < 0.001) compared to HIV-. Use of second-line ART was positively associated with high-sensitivity C-reactive protein (p = 0.002). Although ECG parameters did not differ between HIV- and HIV+/ART+, viral load positively associated with p-wave duration (0.306 (0.018-0.594); p = 0.038), and longer HIV duration (≥5 years) with ST-interval (0.270 (0.003-0.537); p = 0.047) after adjusting for confounding factors. Our findings suggest that HIV and ART are associated with mixed effects on this population's cardiometabolic profile and cardiac electrical activity, underpinning the importance of cardiovascular risk monitoring in PWH.

Denser Retinal Microvascular Network Is Inversely Associated With Behavioral Outcomes and Sustained Attention in Children.

Changes in geometry of the retinal microvascular network, including vessel width, vessel density, and tortuosity, have been associated with neurological disorders in adults. We investigated metrics of the retinal microvasculature in association with behavior and cognition in 8- to 12-year-old children. Digital fundus images of 190 children (48.2% girls, mean age 9.9 years) were used to calculate retinal vessel diameters, fractal dimension, lacunarity, and tortuosity. Parents filled out a Strengths and Difficulties Questionnaire (SDQ) for behavioral screening. Cognitive performance testing included a computerized version of the Stroop test (selective attention), the Continuous Performance (sustained attention), the Digit-Symbol (visual scanning and information-processing speed) and the Pattern Comparison (visuospatial analytic ability) tests from the Neurobehavioral Evaluation System (NES3) battery. Retinal vessel geometry was significantly associated with the SDQ problem score, which increased with 1.1 points (95% CI: 0.3 to 1.9 points) per interquartile (IQR) increment in retinal fractal dimension, and decreased 1.4 points (95% CI: -2.4 to -0.4 points) or decreased 1.0 points (95% CI: -2.1 to 0.1 points) per IQR increment in retinal vascular lacunarity or tortuosity, respectively. Sensitivity analyses showed that results were driven by the hyperactivity/inattention and conduct problem scales of the SDQ. Correspondingly, mean reaction time on the Continuous Performance test increased by 11 ms (95% CI: 4.4 to 17.6 ms) with an IQR increase in fractal dimension. The results indicate that a denser retinal microvascular network, exemplified by a higher fractal dimension and lower lacunarity, are inversely associated with behavioral outcomes and sustained attention in children.