Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292

Retinal Vascular Tortuosity and Diameter Associations with Adiposity and Components of Body Composition.

OBJECTIVE: The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. METHODS: A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. RESULTS: Venular tortuosity and diameter increased by approximately 2% (P < 10-300 ) and 0.6 μm (P < 10-6 ), respectively, per SD increase in BMI, waist circumference index, waist-hip ratio, total body fat mass index, and fat-free mass index (FFMI). Venular associations with adiposity persisted after adjustment for FFMI, whereas associations with FFMI were weakened by FMI adjustment. Arteriolar diameter (not tortuosity) narrowing with FFMI was independent of adiposity (-0.6 μm; -0.7 to -0.4 μm per SD increment of FFMI), while adiposity associations with arteriolar diameter were largely nonsignificant after adjustment for FFMI. CONCLUSIONS: This demonstrates, on an unprecedented scale, that venular tortuosity and diameter are more strongly associated with adiposity, whereas arteriolar diameter relates more strongly to fat-free mass. Different attributes of the retinal microvasculature may reflect distinct roles of body composition and fatness on the cardiometabolic system

Retinal Vascular Tortuosity and Diameter Associations with Adiposity and Components of Body Composition.

OBJECTIVE: The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. METHODS: A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. RESULTS: Venular tortuosity and diameter increased by approximately 2% (P < 10-300 ) and 0.6 μm (P < 10-6 ), respectively, per SD increase in BMI, waist circumference index, waist-hip ratio, total body fat mass index, and fat-free mass index (FFMI). Venular associations with adiposity persisted after adjustment for FFMI, whereas associations with FFMI were weakened by FMI adjustment. Arteriolar diameter (not tortuosity) narrowing with FFMI was independent of adiposity (-0.6 μm; -0.7 to -0.4 μm per SD increment of FFMI), while adiposity associations with arteriolar diameter were largely nonsignificant after adjustment for FFMI. CONCLUSIONS: This demonstrates, on an unprecedented scale, that venular tortuosity and diameter are more strongly associated with adiposity, whereas arteriolar diameter relates more strongly to fat-free mass. Different attributes of the retinal microvasculature may reflect distinct roles of body composition and fatness on the cardiometabolic system

Associations of Retinal Microvascular Diameters and Tortuosity With Blood Pressure and Arterial Stiffness: United Kingdom Biobank.

To examine the baseline associations of retinal vessel morphometry with blood pressure (BP) and arterial stiffness in United Kingdom Biobank. The United Kingdom Biobank included 68 550 participants aged 40 to 69 years who underwent nonmydriatic retinal imaging, BP, and arterial stiffness index assessment. A fully automated image analysis program (QUARTZ [Quantitative Analysis of Retinal Vessel Topology and Size]) provided measures of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiovascular disease risk factors/outcomes were examined using multilevel linear regression to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing within person clustering), adjusted for age, sex, ethnicity, clinic, body mass index, smoking, and deprivation index. Greater arteriolar tortuosity was associated with higher systolic BP (relative increase, 1.2%; 95% CI, 0.9; 1.4% per 10 mmHg), higher mean arterial pressure, 1.3%; 0.9, 1.7% per 10 mmHg, and higher pulse pressure (PP, 1.8%; 1.4; 2.2% per 10 mmHg). Narrower arterioles were associated with higher systolic BP (-0.9 µm; -0.94, -0.87 µm per 10 mmHg), mean arterial pressure (-1.5 µm; -1.5, -1.5 µm per 10 mmHg), PP (-0.7 µm; -0.8, -0.7 µm per 10 mmHg), and arterial stiffness index (-0.12 µm; -0.14, -0.09 µm per ms/m2). Associations were in the same direction but marginally weaker for venular tortuosity and diameter. This study assessing the retinal microvasculature at scale has shown clear associations between retinal vessel morphometry, BP, and arterial stiffness index. These observations further our understanding of the preclinical disease processes and interplay between microvascular and macrovascular disease

Fully Automatic Retinal Vascular Tortuosity Assessment Integrating Domain-Related Information

[Abstract] The fundus of the eye is the only part of the human body that allows a direct non-invasive observation of the circulatory system. Retinal vascular tortuosity presents a valuable potential for diagnostic and treatment purposes of relevant vascular and systemic diseases. This work presents a computational metric for the tortuosity characterization that combines mathematical representations of the vessel segments with anatomical properties of the fundus image such as the vessel caliber, the distance to the optic disc, the distance to the fovea and the distinction between arteries and veins. The evaluation of the prognostic performance shows that the incorporation of the domain-related information allows a reliable characterization of the retinal vascular tortuosity that provides a better representation of the expert perception.This work is supported by the Instituto de Salud Carlos III, Government of Spain and FEDER funds of the European Union through the DTS18/00136 research projects and by the Ministerio de Ciencia, Innovación y Universidades, Government of Spain through the RTI2018-095894-B-I00 research projects; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; ED431G 2019/0

Retinal vascular tortuosity in schizophrenia and bipolar disorder

\u3cp\u3eThe micro-vasculature of retina and brain share common morphological, physiological, and pathological properties. Retina being easily accessible, retinal vascular examination provides an indirect assessment of cerebral vasculature. Considering the high prevalence of vascular morbidity in SCZ and BD a few studies have examined retinal vascular caliber and have reported increased retinal venular caliber in schizophrenia (SCZ). Retinal vascular tortuosity could serve as a better structural measure than caliber as it is static and less susceptible to pulse period variations. However, to date, no study has examined retinal vascular tortuosity in SCZ and bipolar disorder (BD). Hence, we examined retinal vascular tortuosity in comparison with healthy volunteers (HV). We included 255 subjects (78 HV, 79 SCZ, and 86 BD) in the age range of 18 to 50 years. Trained personnel acquired images using a non-mydriatic fundus camera. To measure the average retinal arteriolar tortuosity index (RATI) and retinal venular tortuosity index (RVTI), we used a previously validated, semi-automatic algorithm. The results showed significant differences across the three groups in RATI but not in RVTI; both BD and SCZ had significantly increased RATI compared to HV. There was also a significant difference between SCZ and BD, with BD having higher RATI. If shown to be of predictive utility in future longitudinal studies, it has the potential to identify patients at risk of development of adverse vascular events. As retinal vascular imaging is non-invasive and inexpensive, it could serve as a proxy marker and window to cerebral vasculature.\u3c/p\u3

The role of inflammation in retinal ischaemia

Purpose: The immune cascade is known to contribute to the pathology seen in oxygen induced retinopathy (OIR), however its exact role is poorly defined. We hypothesised that immune cell activation worsens hypoxia and exacerbates the neovascular sequelae seen in ischaemic retinopathy. Methods: We assess the effect of intraperitoneal lipopolysaccharide (IP LPS) injection in OIR mice. Neovascularisation was assessed by measuring the avascular area and neovascular tuft area at P17. Hypoxia was assessed using vessel tortuosity and EF5 hypoxia staining at P14. The activated retinal inflammatory cell population was characterised using immunohistochemistry and flow cytometry. Transgenic mice were bred to delete different subpopulations of inflammatory cells to define their role in hypoxia modulation. RNA sequencing performed on retinal tissue analysed the effect of systemic LPS on retinal cytokines and angiogenesis markers. Results: IP LPS injection at P12 in OIR mice significantly reduced neovascularisation at P17 and hypoxia at P14. Immunohistochemistry revealed an influx of round, CD11b+, lectin stained cells into the retina of LPS treated mice, which on flow cytometry were identified as myeloid cells, being predominantly Cd11b+Ly6Ghi neutrophils. Experimental depletion of the myeloid lineage was achieved using ROSA26eGFP-DTALysMcre, CCL2 and CCR2 knockout mouse lines and anti-CCR2 antibody MC21. However, when these mice were LPS treated, the effects on hypoxia readouts caused by LPS were still seen. Transcriptional profiling of the retina (using RNAseq) revealed a large upregulation in IL1β in the central, hypoxic retina of LPS treated mice. Injection of IL1β at P12 also mimicked the effects of LPS, suggesting that IL1β is a key mediator of the hypoxia reducing effect LPS has in the OIR model. Conclusions: These findings are counterintuitive to the current literature and provide new insight into the role the immune system has on regulating oxygen demand in the retina. This novel approach to reducing hypoxia has the potential to lead to novel therapies targeting hypoxia and preventing neovascularisation in ischaemic eye disease