Autonomic dysfunction and systemic oxidative stress associated with glaucomatous optic neuropathy

There were four principal sections to the work: 1. Investigation of ocular and systemic vascular risk factors in POAG. The principal findings of this work were: a). Glaucoma patients exhibit an anticipatory reaction to the physical stress, similar to subjects at risk for cardiovascular diseases; a blunted BP response and a reduction in ONH blood flow in response to cold provocation was also recorded. b). Silent myocardial ischaemic episodes occurred during peaks in systemic BP and HR. c). Independent of a positive history for cardiovascular diseases, patients suffering from POAG demonstrate a blunt circadian rhythm of the ANS. 2. Assessment of the relationship between vascular and systemic vascular risk factors in GON. The principal findings of this work were: a). POAG patients demonstrate a high sympathetic tonus over a 24-h period. b). POAG patients with lower OBF demonstrate both 24-h systemic BP and HRV abnormalities. c). OBF alterations observed in some glaucoma patients could be either primary or secondary to systemic haemodynamic disturbances and not a consequence of ONH damage. 3. Assessment of the level of systemic anti-oxidant defence in POAG patients. The principal finding of this work was: Patients suffering from POAG demonstrated significantly lower GSH and t-GSH levels than normal controls. 4. Investigation of the effect of treatment with latanoprost 0.005% on visual function and OBF. The findings of this work were: a). Treatment with latanoprost 0.005% resulted in a significant decrease in IOP and increase in OPP. VF damage progression has also been stopped. b). Treatment with latanoprost 0.005% resulted in a significant increase in the OBF parameters measured at the ONH and peripapillary retina levels. Finally, the importance of a clear protocol for managing new POAG cases is highlighted and a clinical conduit is proposed

Ageing effect on flicker-induced diameter changes in retinal microvessels of healthy individuals

Purpose: To compare flicker-induced retinal vessel diameter changes in varying age groups with low cardiovascular risk. Methods: Retinal vascular reactivity to flicker light was assessed by means of dynamic retinal vessel analysis in 57 participants aged 19-30 years, 75 participants aged 31-50 years and 62 participants aged 51-70 years participants. Other assessments included carotid intima-media thickness (c-IMT), augmentation index (AIx), blood pressure profiles, blood lipid metabolism markers and Framingham risk scores (FRS). Results: Retinal arterial dilation amplitude (DA) and postflicker percentage constriction (MC%) were significantly decreased in the oldest group compared to the middle-aged (p = 0.028; p = 0.021) and youngest group (p = 0.003; p = 0.026). The arterial constriction slope (SlopeAC) was also decreased in the oldest group compared to the youngest group (p = 0.027). On the venous side, MC% was decreased in the middle-aged and oldest groups in comparison with the youngest group (p = 0.015; p = 0.010, respectively). Additionally, men exhibited increased arterial DA (p = 0.007), and percentage dilation (MD%, p < 0.001) in comparison with women, but only in the youngest age group. Both AIx and c-IMT scores increased with age (both p < 0.001); however, no correlations were found between the observed differences in the measured retinal vascular function and systemic parameters. Conclusion: In individuals with low cardiovascular risk, there are age-related differences in flicker-induced retinal vessel diameter changes throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the arterial dilatory phase and are only present in young individuals

Microvascular function and oxidative stress in adult individuals with early onset of cardiovascular disease

The current study aims to investigate retinal vascular function and its relationship with systemic anti-oxidative defence capacity in normal individuals versus those with early hypertensive changes according to the current ESC/ESH guidelines. Retinal microvascular function was assessed in 201 participants by means of dynamic retinal vessel analysis. Blood pressure, lipid panel, oxidized (GSH) & reduced glutathione (GSSG) were also evaluated for each participant. Individuals classed as grade 1 hypertension demonstrated higher retinal arterial baseline diameter fluctuation (p = 0.0012), maximum dilation percentage (p = 0.0007), time to maximum constriction (p = 0.0003) and lower arterial constriction slope (p = 0.0131). Individuals classed as high normal and grade 1 hypertension also demonstrated higher time to maximum dilation than individuals classed as optimal or normal. GSH levels correlated negatively with SBP, DBP and MBP values in all participants (p = 0.0010; p = 0.0350 and p = 0.0050) as well as with MBP values in high normal and grade 1 hypertension (p = 0.0290). The levels of GSSG correlated positively with SBP, DBP and MBP values in all participants (p = 0.0410; p = 0.0330 and, p = 0.0220). Our results point to the fact that microvascular alterations can be identifiable at BP values still considered within normal values and go in parallel with the changes observed in the level of oxidative stress

Partially Lazy Classification of Cardiovascular Risk via Multi-way Graph Cut Optimization

Cardiovascular disease (CVD) is considered a leading cause of human mortality with rising trends worldwide. Therefore, early identification of seemingly healthy subjects at risk is a priority. For this purpose, we propose a novel classification algorithm that provides a sound individual risk prediction, based on a non-invasive assessment of retinal vascular function. so-called lazy classification methods offer reduced time complexity by saving model construction time and better adapting to newly available instances, when compared to well-known eager methodS. Lazy methods are widely used due to their simplicity and competitive performance. However, traditional lazy approaches are more vulnerable to noise and outliers, due to their full reliance on the instances' local neighbourhood for classification. In this work, a learning method based on Graph Cut Optimization called GCO mine is proposed, which considers both the local arrangements and the global structure of the data, resulting in improved performance relative to traditional lazy methodS. We compare GCO mine coupled with genetic algorithms (hGCO mine) with established lazy and eager algorithms to predict cardiovascular risk based on Retinal Vessel Analysis (RVA) data. The highest accuracy of 99.52% is achieved by hGCO mine. The performance of GCO mine is additionally demonstrated on 12 benchmark medical datasets from the UCI repository. In 8 out of 12 datasets, GCO mine outperforms its counterpartS. GCO mine is recommended for studies where new instances are expected to be acquired over time, as it saves model creation time and allows for better generalization compared to state of the art methodS

Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients:a case for autonomic failure?

PURPOSE. To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS. Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40°C warm water followed by 4°C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS. The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40°C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40°C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS. Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients

Retinal Microvascular Abnormalities and Systemic Arterial Stiffness Are the First Manifestation of Cardiovascular Abnormalities in Patients with Untreated Moderate to Severe Obstructive Sleep Apnoea and with Low to Intermediate Cardiovascular Risk-A Pilot Study

This study aimed to investigate macro- and microvascular function parameters and their relationship with known markers of cardiovascular risk in patients with untreated moderate to severe obstructive sleep apnoea (OSA). Fourteen patients with moderate to severe OSA and fourteen controls were included in the present study. General assessments included BMI, systemic blood pressure (BP) and circulating markers for oxidative stress and endothelial function. Additional assessments included 24 h BP and heart rate monitoring, as well as the assessment of heart rate variability. Macro- and microvascular assessments included augmentation index, carotid intima-media thickness, brachial artery flow-mediated dilation, as well as various retinal microvascular function assessments, using the Dynamic Retinal Vessel Analyzer. All participants completed the Short Form Health Survey, Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale. The results show that, in comparison to controls, BMI ( = 0.003) and AIx ( = 0.025) were significantly higher in the OSA group. There was, however, no significant difference between groups with regard to other measured systemic general, vascular and circulatory parameters (all > 0.05). Nevertheless, the retinal microvascular function showed various alterations in the OSA patients, including a delayed reaction time in response to flicker ( = 0.047), as well as a decreased dilation amplitude ( = 0.004), dilation slope ( = 0.004), and post-flicker constriction ( = 0.015). In addition, the observed Slope alterations correlated negatively with BMI values only in the OSA group (r = -0.46, = 0.045). In conclusion, individuals with untreated moderate to severe OSA but without overt CVD, exhibit signs of increased arterial stiffness and retinal microvascular dysfunction, which can be early indicators for future vascular complications

Author response: can vascular function be assessed by the interpretation of retinal vascular diameter changes?

A protocol with repeated stimulation cycles should be analyzed stepwise, in that each stimulation is evaluated, and a reaction pattern is identified. No two subjects will react identically, in that dilation and recovery times can vary; however, this is not reason enough to abandon a multiple stimulation cycle with fixed recovery and stimulation times. Furthermore, it enables us to examine and determine the range in which a normal subject will be placed and can then be compared to different pathophysiological states (i.e., smokers and different diseases). The purpose of our paper was to highlight the importance of evaluating these different cycles and the danger of false interpretation when averaging results. There are many different ways of evaluating dilatory responses and elasticity, but each of them must be carefully evaluated and should not be overaveraged, which can result in a loss of sensitivity and specificity

Oxysterols and Retinal Microvascular Dysfunction as Early Risk Markers for Cardiovascular Disease in Normal, Ageing Individuals

The aim of the present paper is to assess the relationship between oxysterol levels and retinal microvascular function in individuals of various age groups, free of clinically evident diseases. Forty-two apparently healthy individuals were included in the present study (group 1: 19–30 years, group 2: 31–50 years, and group 3: 51–70 years). Retinal microvascular function was assessed using the dynamic retinal vessel analyzer (DVA, IMEDOS GmbH, Jena, Germany). Fasting plasma was obtained from all subjects and quantification of monohydroxy and dihydroxy oxysterols assessment was performed using LC-MS/MS following reverse phase chromatography. A Griess assay was used to evaluate the Nitric Oxide (NO) concentration in all individuals. The glutathione redox ratio was also analyzed by means of whole blood glutathione recycling assay. In all participants, the levels of 7-Ketocholesterol, 25-hydroxycholesterol and 7β-hydroxycholesterol correlated significantly and positively with the time to maximum arteriolar dilation. In addition, 25-hydroxycholesterol and 7β-hydroxycholesterol negatively correlated to the percentage of maximum arteriolar dilation. A negative correlation was observed for 27-hydroxycholesterol and 7β-hydroxycholesterol with microvascular arteriolar constriction. These results suggest that, with age, abnormal oxysterol levels correlate with early changes in microvascular bed function. This relationship could signal early risk for cardiovascular diseases (CVDs) in an ageing population

The effect of voluntary fasting and dehydration on flicker-induced retinal vascular dilation in a healthy individual: a case report

INTRODUCTION: Dynamic retinal vessel analysis represents a well-established method for the assessment of vascular reactivity during both normal conditions and after various provocations. We present a case where the subject showed abnormal retinal vessel reactivity after fasting voluntarily for 20 hours. CASE PRESENTATION: A healthy, 21-year-old man who fasted voluntarily for 20 hours exhibited abnormal retinal vascular reactivity (dilation and constriction) after flicker provocation as measured using the Dynamic Retinal Vessel Analyser (Imedos, Jena, Germany). CONCLUSION: The abnormal vascular reactivity induced by fasting was significant; abnormal levels of important nutrients due to fasting and dehydration could play a role through altering the concentration of vasoactive substances such as nitric oxide. This hypothesis needs further investigation

Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30–55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1