Static Vessel Analysis Research Articles

Retinal vessel analysis in vascular occlusions of the eye

Aims/Purpose: This cohort study investigates how the static and dynamic vessel parameters differ in patients with vascular occlusions and if there are any variations between the different types of vessel occlusion.Methods: Patients with the diagnosis of branch retinal artery obstruction BRAO, central retinal artery obstruction CRAO, branch retinal vein obstruction BRVO, central retinal vein obstruction CRVO, anterior ischaemic optic neuropathy AION and any combination of these Combo were included in our study. During their inpatient stay for cardiovascular diagnostics all patients were examined via static and dynamic vessel analysis (IMEDOS Health GmbH, Jena) to obtain the arteriovenous ratio (AVR), the central retinal artery equivalent (CRAE), the central retinal vein equivalent (CRVE) and the flicker light induced dilation of the retinal arteries (FLA) and veins (FLV). The vessel density was determined via OCT angiography (Heidelberg Engineering GmbH, Heidelberg).Results: 34 patients (70% male; 30% female; mean age 69.6 ± 11.3 years) with 9 (26.5%) CRVO, 8 (23.5%) AION, 5 (14.7%) BRAO and 4 (11.8%) CRAO, BRVO and Combo each have been included. The best visual acuity (BCVA) of the diseased eye differed significantly between the groups (AION 0.41 ± 0.61, CRAO 2.40 ± 0.20, BRAO 0.16 ± 0.05, CRVO 0.81 ± 0.86, BRVO 0.18 ± 0.10, Combo 1.53 ± 0.68; p < 0.001) whereas the BCVA of the healthy eyes were comparable. The CRVE showed a significant difference between the groups CRAO – CRVO (p = 0.008), CRAO – Combo (p < 0.001) and BRAO–Combo (p = 0.026). The FLV of the diseased eye was significantly higher in patients with AION than in the CRAO group (p = 0.049). The parameters of the static vessel analysis of the healthy eyes were comparable.Conclusions: Preliminary analysis shows significant differences of individual parameters of the retinal vessel analysis between different types of vascular occlusion. The diagnostic and research benefit for the individual patient remains to be further evaluated.

Introduction to static vessel analysis

This talk will provide you with an overview of static retinal vessel analyses. Digital photography, automated vessel segmentation and analyses have revolutionized the field of retinal vessel analyses rapidly. Retinal vessel calibre changes allow for non‐invasive study of the microcirculation in vivo. The study of the retinal microcirculation has shown its potential in cardiovascular risk assessment, allowed for observation of changes in systemic health and capture changes in physical activity. This session is aimed for those new to retinal vessel analyses using fundus images.

VascuFit: vascular effects of non-linear periodized exercise training in sedentary adults with elevated cardiovascular risk – protocol for a randomized controlled trial

BackgroundEarly vascular aging (EVA) is increasingly prevalent in the general population. Exercise is important for primary cardiovascular prevention, but often insufficient due to ineffective training methods and a lack of biomarkers suitable to monitor its vascular effects. VascuFit will assess the effectiveness of non-linear periodized aerobic exercise (NLPE) in a non-athletic sedentary population to improve both established and promising biomarkers of EVA.MethodsForty-three sedentary adults, aged 40–60 years, with elevated cardiovascular risk will either engage in 8 weeks of ergometer-based NLPE (n = 28) or receive standard exercise recommendations (n = 15). The primary outcome will be the change of brachial-arterial flow-mediated dilation (baFMD) after versus before the intervention. Secondary outcomes will be the change in static vessel analysis (SVA; clinical biomarker of microvascular endothelial function), endomiRs (microRNAs regulating key molecular pathways of endothelial cell homeostasis) and circulating cellular markers of endothelial function (mature endothelial cells, endothelial progenitor cells). Tertiary outcomes will be the change in sphingolipidome, maximum oxygen capacity, and traditional cardiovascular risk factors (blood pressure, triglycerides, cholesterol, fasting glucose, high-sensitivity C-reactive protein).DiscussionWe expect an improvement of baFMD of at least 2.6% and significant pre-post intervention differences of SVA and endomiRs as well as of the tertiary outcomes in the intervention group. VascuFit may demonstrate the effectiveness of NLPE to improve endothelial function, thus vascular health, in the general sedentary population. Furthermore, this project might demonstrate the potential of selected molecular and cellular biomarkers to monitor endothelial adaptations to aerobic exercise.Trial registrationThe trial was registered on www.clinicaltrials.gov (NCT05235958) in February 11th 2022.

Vascular ophthalmopathies - an interdisciplinary task

Retinal microvascular function is highly depending on macrovascular circulation and especially on blood pressure variability and nocturnal blood pressure. The eyes are more subject to central hemodynamics compared to peripheral pressures. Pulse wave analysis is essential here and can reveal masked aortic hypertension. Morphological and functional changes of retinal vessels are detected today in high resolution by digital imaging techniques. Early hypertensive changes can be visualized best by laser scanning multi-color devices, and the vessel diameters (AV-Ratio) are measured precisely by static vessel analysis. Functional disorders of vascular motility are delineated reproducibly by devices for dynamic vessel analysis. Also functional effects of cardiovascular therapy measures can be judged by these means: micro- meets macrocirculation.

Age‐related Changes in Systemic Circulation Promote Vascular Maladaptation and Impair Vascular Reactivity in Retinal and Brain Circulation in Older Adults

IntroductionNormal brain function requires appropriate provision of oxygen, glucose, and other nutrients. This requirement is fulfilled through continuous adjustment of cerebral blood flow (CBF), the process also known as neurovascular coupling (NVC). Therefore, impairment of the resting CBF or impairment of NVC in the brain may be responsible for the development of vascular cognitive deficits in aging. A novel method, Dynamic Retinal Vessel Analysis (DVA) allows evaluation of NVC responses in the retinal circulation in response to photoreceptor stimulation. Considering that human retina shares similar embryologic origins with the central nervous system, this approach may provide a novel and non‐invasive tool to screen subjects at risk for development of vascular cognitive impairment. In this study, we hypothesize that examination of retinal vessels may provide a proxy measure of the microcirculatory health of the brain. We test whether the arterio‐venous ratio (AVR) and NVC measured in the retina correlate with age, cognitive function, central and cerebrovascular hemodynamics.MethodsFor our study, we enrolled 44 healthy adults 23–86 years of age. DVA and static vessel analysis was performed using a mydriatic retinal camera to determine retinal NVC and AVR. Transcranial Doppler Sonography (TCD) was used to assess resting CBF velocity and pulsatility in the middle cerebral artery (MCA). Pulse Waveform Analysis was used to measure central hemodynamic pressures. and stiffness (augmentation index, AIx) was calculated from these results. Cognitive performance was assessed using Cambridge Neuropsychological Cognitive Test Automated Battery (CANTAB), specifically, Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests. Spearman’s correlation between variables was used for statistical analysis.ResultsRetinal NVC showed negative (rho=−0.48, p=0.02), and MCA pulsatility showed positive (rho=0.69, p<0.01) correlation with aortic pulse pressure. Neither of these vascular parameters correlated with central arterial stiffness (AIx). Older age was associated with decreased cognitive performance: total errors on PAL test (PALTEA28, rho=0.49, p<0.01),mean latency to the correct response during DMS (DMSMLAD, rho=0.46, p<0.01), and correct responses in DMS (DMSPC rho=−0.43, p<0.01). AVR correlated negatively with PALTEA28 (rho=−0.48, p<0.01) and positively with DMSPC (rho=0.64, p<0.01), retinal arteriolar dilation correlated negatively with DMSMLAD (rho=−0.32, p=0.04).ConclusionsOur results demonstrate that age‐related changes in the macrocirculation lead to the maladaptation and decreased reactivity of retinal microcirculation. The association between retinal‐, and brain hemodynamics, together with cognitive performance suggests that the retinal microcirculation may reflect the health of the cerebral microcirculation.

Effects of a school-based physical activity program on retinal microcirculation and cognitive function in adolescents

ObjectivesTo investigate the effect of combined aerobic and coordinative exercise on retinal microcirculation and its association with changes in cognitive performance in healthy adolescents. DesignUsing cluster-randomization (on class-level), 36 participants were allocated to an exercise group (EX) performing a 20-min aerobic and coordinative exercise session on each school day over a period of 8 weeks or a control group, which was encouraged to have social interactions (CON). MethodPrior to and following the intervention period, central retinal arteriolar (CRAE) and venular diameters (CRVE) were assessed by use of a static vessel analyzer. Additionally, a computer-based version of the Stroop Color-Word task was administered to assess inhibitory control. ResultsThe statistical analysis revealed that EX compared to CON showed higher CRAE at post-test, when pre-test values were accounted for, F(1,32)=4.92, p=0.036, η2=0.130. In contrast, no such effect was reported for CRVE. With regard to cognitive performance, a greater reduction of reaction time on the Stroop task was observed in EX relative to CON, F(1,30)=8.58, p=0.006, η2=0.222. The increase in CRAE was significantly correlated with a decrease of reaction time on trials demanding inhibitory control, even after adjusting for covariates, r(31)=−0.438, p=0.011. ConclusionsA structured exercise program leads to a widening of retinal arteriolar diameters, which is associated with improvements in inhibitory control. Consequently, daily exercise sessions performed during the school break-time can be recommended for promoting both cardiovascular and cognitive health in adolescents.

Effects of different endurance exercise modalities on retinal vessel diameters in unipolar depression

BackgroundPsychiatric disorders are associated with a high prevalence of cardiovascular disease. Regular exercise is known to reduce depressive symptoms and improve vascular function, in turn lowering cardiovascular risk. We aimed to investigate the effects of different exercise modalities on retinal vessel diameters as a microvascular biomarker and depression severity index in patients suffering from unipolar depression. Methods23 patients (female: 19, male: 4, age: 36.7, Beck-Depression-Inventory-II (BDI-II) score: 30.7) were enrolled in this two-armed randomized controlled trial. Static vessel analysis was performed to obtain central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents and the arterio-venous diameter ratio (AVR). Maximal bicycle ergometer exercise testing yielded maximal fitness parameters. Patients were assigned to either high intensity low volume (HILV) or moderate continuous aerobic training (MCT). Both intervention groups trained three times a week during a 4-week intervention period. ResultsModerate interaction effects were found for AVR (ɳp2 = 0.12) whereby HILV showed a larger increase in AVR (HILV: pre: 0.89 (0.04), post: 0.91 (0.04), SMD = −0.50) compared to MCT (MCT: pre: 0.85 (0.06), post: 0.86 (0.05), SMD = −0.18). Parallel group trials revealed a 67% possibly beneficial effect of HILV over MCT. Moderate interaction effects on depression severity reduction (ɳp2 = 0.06) were found, whereby the effect size was slightly larger in MCT. ConclusionBoth exercise interventions improved AVR as well as BDI-II. HILV may be more effective in improving cerebrovascular health. The exercise-induced effects on retinal vessel diameter changes were relatively small and the clinical relevance remains to be investigated in larger and longer-term exercise trials.

Experimental Characterization and Correlation of Mayer Waves in Retinal Vessel Diameter and Arterial Blood Pressure.

Retinal vessels show various biological temporal variations that can impact diagnosis using a static vessel analysis. In this study, Mayer waves in the retinal vessel diameter and arterial blood pressure (BP) signals were characterized, and the temporal correlation between these two modalities was investigated. The arterial and venous vessel diameters and arterial BP were recorded simultaneously on human subjects. The obtained vessel diameters showed vasomotion amplitudes over time. The vessel diameter and BP signals contained multiple signals in the frequency domain and varied over time. The signal characteristics were similar within the measurements. The BP and arterial and venous vessel diameters were correlated. The highest correlation values between the signals were observed for shifts of 1 or 0 periods. The spectrum and amplitudes of the Mayer waves showed a high variability. The Mayer waves in the retinal vessel diameters showed the same characteristics as those in the arterial BP. A temporal dependency between the oscillations in the arterial BP and retinal vessel diameters was shown.

Cross-sectional association between oral health and retinal microcirculation.

To investigate the relation between oral health status and microcirculation, we analysed the association between periodontitis and number of teeth with retinal vessel diameters in a population-based study. We analysed data from the Study of Health in Pomerania-TREND (SHIP-TREND). All subjects (3,183 for number of teeth, 3,013 for mean probing depth and 2,894 for mean attachment level) underwent nonmydriatic funduscopy and dental examination. We measured central retinal arteriolar (CRAE), venular (CRVE) vessel diameters and calculated arterio-venous ratio (AVR) from static vessel analysis (SVA). Periodontal status was assessed using the case definition of the Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Data were analysed by linear (CRAE, CRVE, AVR) and logistic regression (AVR<0.8) adjusted for age, sex, smoking status, alcohol consumption, body mass index, systolic blood pressure, hsCRP and type-2-diabetes mellitus. Only in men, significant associations were found between periodontal and retinal conditions. Severe periodontitis [β=-0.0120 (-0.0218; -0.0007 95%-CI)] and mean probing depth [β=-0.0054 (-0.0105; -0.0002 95%-CI)] were inversely associated with AVR; severe periodontitis [β=3.80 (0.61; 6.98 95%-CI)], mean probing depth [β=1.86 (0.23; 3.49 95%-CI)] and mean attachment level [β=1.31 (0.34; 2.27 95%-CI)] with CRVE and mean attachment level with CRAE [β=0.91 (0.14; 1.69 95%-CI)]. Our results point towards an association between periodontal conditions and AVR in men. Periodontitis may impact microvascular endothelium function. Improving oral health to reduce periodontitis might lead to reduced risk for other age-related diseases.

Static and dynamic retinal vessel analyses in patients with stroke as compared to healthy control subjects

PurposeThe retinal microcirculatory bed shares anatomical and physiological characteristics with the cerebral circulation. Static and dynamic changes in the retinal blood vessels can mirror cardio‐ and cerebrovascular events. The aim of the study was to underpin the relevance of retinal analysis for stroke research.Methods18 stroke patients and 16 age‐matched healthy control subjects were included in the present study. Retinal image acquisition was done with a Zeiss fundus camera FF 450plus. Static vessel analysis was done using IFLEXIS software provided by VITO (www.iflexis.com). Retinal vessel dimensions and geometric dimensions were determined. A retinal arteriole and a retinal venule were examined before and after flicker light stimulation for 60 sec. Flicker response, the relative change of vessel diameter due to flicker light stimulation, was calculated using Dynamic Vessel Analysis by imedos (www.imedos.de).ResultsCentral Retinal Arterial Equivalent (CRAE) was significant smaller in stroke patients when compared to the control group, whereas Central Retinal Venular Equivalent (CRVE) was comparable between the groups. Arteriovenous ratio (AVR) was significantly smaller in the stroke group. The analysis further showed significantly smaller daughter arteriolar branches and larger venular branch angles in stroke patients. Dynamic vessel analysis found reduced arteriolar diameters in stroke patients. Response to flicker light was smaller in stroke patients but this difference did not reach level of significance.ConclusionsOur pilot study indicates that retinal analysis is a non‐invasive and convenient tool that is relevant to study microvascular changes in stroke patients The importance of retinal changes as a risk factor for stroke or for patient stratification is now being addressed in follow‐up studies.

Dynamic functionality and static changes of retinal vessels in diabetic patients treated with intravitreal ranibizumab.

To investigate the short-term effects of intravitreal ranibizumab on retinal vessel functionality in patients with diabetic macular edema (DME) by Dynamic Vessel Analyzer (DVA). Patients presenting with DME were enrolled in the study. All patients underwent a complete ophthalmic evaluation, including optical coherence tomography and dynamic and static vessel analysis, using the DVA before (baseline), 1week and 1month after administration of intravitreal ranibizumab. DME subject were compared with diabetic retinopathy (DR) without DME subjects, and with normal non diabetic subjects (controls) matched for age and sex. A total of 45 eyes of 45 subjects (15 eyes for each group) were included in the analysis. In DME patients, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1week. Mean central retinal artery equivalent (CRAE) of DR patients without DME was significantly different from baseline and week 1 of DME eyes. In healthy control subjects, CRAE was significantly different from CRAE at baseline and 1week on DME patients, but not significantly different from DR patients without DME. Using DVA in patients with DME, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1week in DME eyes. A significant reduction in arterial vessels could be demonstrated in DME patients compared to DR patients without DME and controls.

The association of socio-economic factors with physical fitness and activity behaviours, spinal posture and retinal vessel parameters in first graders in urban Switzerland

ABSTRACTSocio-economic status during childhood has been shown to be a strong predictor of adult health outcome. Therefore, we examined associations of parental educational level, household income and migrant background with physical fitness, spinal flexibility, spinal posture as well as retinal vessel diameters in children of an urban Swiss region. A total of 358 first graders of the Swiss canton Basel-Stadt (age: 7.3, SD: 0.4) were examined. Physical fitness (20 m shuttle run test, 20 m sprint, jumping sidewards and balancing backwards), spinal flexibility and spinal posture (MediMouse®, Idiag, Fehraltdorf, Switzerland) and retinal microcirculation (Static Retinal Vessel Analyzer, Imedos Systems UG, Jena, Germany) were assessed. Parental education, household income, migrant background and activity behaviour were evaluated with a questionnaire. Parental education was associated with child aerobic fitness (P = 0.03) and screen time (P < 0.001). Household income was associated with jumping sidewards (P = 0.009), balancing backwards (P = 0.03) and sports club participation (P = 0.02). Migrant background was associated with BMI (P = 0.001), body fat (P = 0.03), aerobic fitness (P = 0.007), time spent playing outdoors (P < 0.001) and screen time (P < 0.001). For spinal flexibility and retinal vessel diameter, no associations were found (0.06 < P < 0.8). Low parental education, low household income and a migrant background are associated with poor physical fitness, higher BMI and body fat percentage and low-activity behaviour.

DYNAMIC AND STATIC RETINAL VESSEL ANALYSES IN PATIENTS WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION.

To investigate the vasomotor responses and diameter of retinal vessels in patients with macular edema secondary to retinal vein occlusion (RVO). A total of 18 eyes of 18 RVO patients were consecutively included and compared with age- and sex-matched controls. Participants underwent an examination with optical coherence tomography and dynamic and static retinal vessel analyses using the Dynamic Vessel Analyzer. Dynamic vessel analysis in RVO showed mean maximum venous and arterial dilation of 2.22 ± 1.23% and 1.87 ± 1.41%, respectively, as compared with 5.05 ± 2.75% (P = 0.001) and 3.95 ± 1.44% (P = 0.0004), respectively, in controls. Static retinal vessel analysis in RVO revealed a mean arteriovenous ratio (AVR) of 0.74 ± 0.09 versus 0.90 ± 0.04 (P < 0.0001) in controls. Mean AVRs of occluded and nonoccluded quadrants in RVO were 0.71 ± 0.13 and 0.85 ± 0.19, respectively; in the corresponding quadrants of controls, mean AVRs were 0.90 ± 0.19 (P < 0.0001) and 0.86 ± 0.17 (P = 0.89), respectively. In branch RVO patients, mean AVRs of occluded versus nonoccluded quadrants were 0.70 ± 0.06 and 0.90 ± 0.22 (P = 0.002), respectively. In patients with macular edema secondary to RVO, dynamic vessel analysis showed an impairment of both venous and arterial motility and/or reactivity and static vessel analysis showed a reduced AVR indicating a general enlargement of the retinal venous network. Moreover, in branch RVO patients, static analysis demonstrated that retinal vessels could actually be uninvolved by the occlusive process in areas spared by disease.

High serum thyrotropin levels are associated with retinal arteriolar narrowing in the general population.

Recent studies have shown associations of hypothyroidism with arterial blood pressure, atherosclerosis, and inflammation. Based on these pathways, there might also be an association between hypothyroidism and retinal arteriolar narrowing (RAN), a marker of microvascular damage from hypertension, atherosclerosis, and inflammation. Against this background, the aim of this study was to investigate the putative association between serum thyrotropin (TSH) levels and RAN defined by arterio-venous ratio (AVR) from static vessel analysis. We used data from 3189 individuals from the second population-based cohort of the Study of Health in Pomerania (SHIP-TREND-0). Thyroid function was defined according to serum TSH and serum diiodothyronine (3,5-T2) levels. Low and high serum TSH levels were defined by the cutoffs 0.3 mIU/L and 3.0 mIU/L. Fundus photography of the central retina was recorded with a nonmydriatic camera, and images were evaluated by one experienced reader. An AVR <0.8 was defined as decreased. Serum TSH levels, low and high TSH, and serum 3,5-T2 levels were associated with AVR by linear regression and with AVR <0.8 by Poisson regression, both adjusted for age, sex, cigarette smoking, alcohol consumption, and intake of beta-blockers. Serum TSH levels were significantly associated with AVR (β=-0.028 [CI -0.049 to -0.007]; p=0.009) and with a decreased AVR <0.8 (relative risk=2.05 [CI 1.13-3.73]; p=0.019). Individuals with high TSH had a 1.43 higher risk for a decreased AVR ([CI 1.04-1.96]; p=0.027) than individuals with serum TSH levels within the reference range. Serum 3,5-T2 levels were also associated with a decreased AVR (relative risk for an increase of 1 nM=0.45 [CI 0.23-0.87]; p=0.017). Our results substantiate evidence for an association between hypothyroidism and RAN. Potential mechanisms explaining this association are long-term hypertension, atherosclerotic processes, and inflammation.

Comparison of Two Non-mydriatic Fundus Cameras to Obtain Retinal Arterio-venous Ratio

Purpose: To analyze device-dependent variability of two non-mydriatic fundus cameras to obtain arterio-venous ratio (AVR), central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE) in static vessel analysis (SVA).Methods: We examined 53 participants (29 men, 24 women; median age 46 years) of the Study of Health in Pomerania (SHIP). We took 45° optic-disc-centered fundus images of the right eye with two different non-mydriatic fundus cameras. The first photograph was obtained from the TRC-NW 200, the second from the OCT 2000 (both Topcon Corporation, Tokyo, Japan). One experienced grader graded image quality from 1 “ideal quality” to 5 “not analyzable” and determined AVR, CRAE, and CRVE with the software Vesselmap3 (Imedos, Jena, Germany).Results: Average image quality was 1.8 for the TRC-NW 200 and 1.6 for the OCT 2000. AVR could not be determined in 5 images of the TRC-NW 200 due to low image quality, while six images of the OCT 2000 were not analyzable. The difference between AVR taken from two different non-mydriatic cameras was 0.01 ± 0.03 in Bland-Altman plots. The difference between CRAE was 0.17 ± 10.15 and between CRVE was −2.32 ± 11.76.Conclusions: The two different non-mydriatic cameras showed good agreement with respect to image quality. When using the same reading software, AVR, CRAE, and CRVE agreed well. Thus, funduscopy and SVA seem to be robust against inter-device variability. As a result, device dependency can remain unconsidered in follow-up examinations with different technical equipment. However, variability might impact more with devices from different manufacturers.

Study of health in Pomerania (SHIP-Trend): : Important aspects for healthcare research in ophthalmology

Epidemiological studies continue to receive growing attention in health services research. How can ophthalmological health services research benefit from the Study of Health in Pomerania (SHIP)? The SHIP is a population-based, epidemiological project conducted in the northeast of Germany. In 1997 a random sample of 6,265 eligible subjects was enrolled for the first SHIP cohort. Between 1997 and 2001 baseline examinations were performed, followed by 5-year follow-up from 2002 to 2006, from 2008 to 2012 and from 2014. A second independent sample of 8,016 eligible subjects was enrolled in 2008. Baseline examinations of this new cohort (SHIP-Trend) were conducted between 2008 and 2012 and the first follow-up is scheduled for 2015. Included in SHIP are a large variety of different assessments including eye examinations. All participants are subjected to non-mydriatic funduscopy and static vessel analysis (SVA). A total number of 4,420 subjects participated in the interdisciplinary baseline examinations of SHIP-Trend. Standardized fundus photography was performed with a non-mydriatic camera in 3,934 subjects. Estimations of the prevalence of major eye diseases may provide valid indicators for healthcare provision within healthcare research. New concepts of prevention with a strengthened integration of ophthalmological diagnostics can be identified from the widespread spectrum of different healthcare examinations. Regional differences in the efficiency of healthcare provision can be evaluated with comparative studies between different German populations.

The short‐term effect of flavonoid‐rich dark chocolate on retinal vessel diameter in glaucoma patients and age‐matched controls

To investigate the effect of flavonoid-rich dark chocolate and non-flavonoid-rich white chocolate on retinal vessel diameter in glaucoma patients and age-matched controls. Thirty glaucoma patients and 30 age-matched subjects were assigned to dark or white chocolate by randomization with forced equal distribution. The number in each of the four groups was 15. Measured parameters included systemic blood pressure (BP), blood glucose levels, static retinal vessel analysis, as measured by central retinal artery equivalent (CRAE) (which relates to the diameter of the central retinal artery), central retinal vein equivalent (CRVE) (which relates to the diameter of central retinal vein) and the arterio-venous ratio (AVR), which represents the CRAE/CRVE ratio, dynamic retinal vessel analysis as measured by the change in vessel diameter in response to flicker light stimulation. Three recording cycles from each were averaged. Blood pressure parameters (systolic BP, diastolic BP and pulse), IOP and blood glucose levels did not differ significantly between both groups before and after consumption of white or dark chocolate. Static vessel analysis did not show any significant changes in CRAE, CRVE or AVR before and after dark or white chocolate in both groups (p > 0.05). Mean dilatation of the venules in the control group was 3.2 ± 0.9 % before dark chocolate and 4.2 ± 1.4 % after dark chocolate intake, which was statistically significantly different (p = 0.01). Mean dilatation of the arterioles in the control group was 2.8 ± 1.8 % before dark chocolate and 3.5 ± 1.8 % after dark chocolate intake with a trend to statistical significance (p = 0.14), but not reaching the significance level. Mean diameter changes in the glaucoma group did not show any significant differences after dark chocolate consumption. The present study showed a significant improvement of venous vasodilatation 2 hr after dark chocolate intake in the control group, but not in the glaucoma group. This effect might be indicative of an increased bioavailability of nitric oxide (NO) after dark chocolate consumption. The lack of finding a significant venous response after dark chocolate in the glaucoma group might be related to the already impaired endothelial function in these patients.

Acute and chronic effects of marathon running on the retinal microcirculation

ObjectivePrevious studies indicate an association between marathon running and premature atherosclerosis. Retinal vessel diameter alterations, in particular narrower arterioles and wider venules, reflect early stages of atherosclerosis, but the influence of marathon on the retinal microcirculation is unknown. MethodsRetinal vessel diameters were measured in 85 male runners (age 31–60 years; previous marathons 0–56) and in 45 age-matched healthy controls using a static vessel analyzer. In runners, diameters were also measured immediately and 24h after a marathon. Cardiovascular risk profiles, clinical chemistry and, in a subgroup of 46 runners, peripheral arterial wave reflections were also assessed. ResultsRunners had larger arterioles (median 196μm (IQR 25) vs. 190(25); p=0.068) and smaller venules (222(25) vs. 224(18); p=0.063) than controls, resulting in a significantly increased arteriolar-to-venular ratio (AVR; 0.89(0.08) vs. 0.85(0.07); p<0.001). In runners, retinal vessel diameters were not associated with body mass index, blood pressure, smoking, lipids or training history, and no differences were observed between the lowest (0.71–0.84) and highest (0.95–1.06) AVR quintiles. The marathon run induced a significant increase of AVR (0.91 (0.09); p=0.007) due to larger arteriolar than venular dilatations, correlating weakly to race duration (r=0.32; p=0.003) and to a lower increase in leucocytes (r=−0.35; p=0.001). Vessel diameters normalized 24h after the race. Augmentation index and pulse pressure decreased significantly after the race, but no associations with retinal vessel diameters were observed. ConclusionMarathon running is not associated with an impairment of the retinal microcirculation. These findings contrast previous reports on atherosclerotic alterations of peripheral vessels.

Exercise-induced alterations of retinal vessel diameters and cardiovascular risk reduction in obesity

BackgroundThe retinal microcirculation is affected early in the process of atherosclerosis and retinal vessel caliber is an emerging cardiovascular risk factor. Obesity is associated with vascular dysfunction. Here, we investigate the effect of regular exercise on retinal vessel diameters in lean and obese runners. We analyze a possible link to alterations of the nitric oxide (NO)-asymmetric dimethylarginine (ADMA) pathway. MethodsRetinal vessel diameters were assessed by means of a static vessel analyzer (SVA-T) in 15 obese athletes (OA), 14 lean amateur athletes (AA) and 17 lean elite athletes (EA) following a 10 week training program. ADMA serum levels were detected by ELISA and dimethylarginine dimethylaminohydrolase (DDAH) -1/-2 mRNA-expression in peripheral mononuclear cells (PBMC) was analyzed by real time PCR. ResultsAt baseline, the mean (±SD) arteriolar to venular diameter ratio (AVR) was impaired in obese (OA: 0.81±0.05) compared to lean subjects (AA: 0.87±0.07; EA: 0.94±0.05). The individual fitness levels correlated with AVR (rho=+0.66; P<0.001) and the training program improved AVR in all groups (P<0.001), normalising AVR in the obese (OA: 0.86±0.1). A training-induced arteriolar dilatation was found in OA (P=0.01), which was accompanied by a significant decrease of ADMA levels (0.56±0.12–0.46±0.12μmoll−1; P<0.028). DDAH-1 mRNA levels in PBMC increased in all groups (P<0.01). ConclusionsCardiovascular fitness and body composition affect retinal vessel diameters. Regular exercise reverses the subclinical impairment of the retinal microvasculature in obesity by inducing retinal arteriolar dilatation. The NO/ADMA pathway may play a key role in the training-induced improvement of microvascular function, which has the potential to counteract progression of small vessel disease.

The eye, the kidney and microcirculation

When Hermann von Helmholtz invented the direct ophthalmoscope in 1850, he opened the door to a non-invasive visualization of human microcirculation in vivo at the retina (Figure 1). Only a few years later, on 4 September 1864, a young man presented a talk on ‘The blood vessels of the human eye’ at the Heidelberg Ophthalmology Congress—his namewas Theodor Leber, and today, he is regarded as one of the founders of ophthalmic research. Only relatively minor changes have been made subsequently to Leber’s original anatomical drawings of the ocular vasculature [1]. In 1904, W. M. Bayliss was the first to describe the myogenic constriction of arterioles when transmural pressure is elevated [2]. This so-called ‘Bayliss effect’ is a central mechanism of the autoregulation to maintain blood flow in an organ despite variations in perfusion pressure. The kidney is the classical organ in which autoregulation of blood flow with changes in perfusion pressure has been demonstrated [3,4]. The retina provides an opportunity for the in vivo investigation of a part of human circulation. It has been shown that blood flow in the human retina is autoregulated [5], and with modern technology, the retina offers the unique chance to measure the ‘Bayliss effect’ on a non-invasive basis in human retinal arterioles [6]. As it is generally accepted that the retinal vessels have no functioning autonomic innervation beyond the lamina cribrosa, this autoregulation occurs in response to changes in perfusion pressure or in response to metabolic stimuli. The mammalian retina has been found to possess an unusually high rate of glycolysis [7] and oxygen consumption [8], with this activity fuelling the active transport processes that maintain the ionic gradients necessary for visual transduction and electrical activity. As it is widely accepted that cerebral blood flow is spatially and temporally coupled to brain function and metabolism [9], the same neurovascular coupling was postulated for the retina [10]. Different measuring methods have been developed to quantify ocular perfusion. They have profoundly changed our understanding of the regulation and dysregulation of perfusion of the eye, and given new insights into the pathogenesis of ocular diseases. These findings were brought to the attention of ophthalmologists, and in clinical practice and research, use of these technologies was limited to the ophthalmic community. However, some devices have demonstrated their functionality in the hands of neurologists and diabetologists. The Dynamic Retinal Vessel Analyzer (DVA, Imedos, Jena, Germany) consists of a modified CCD camera fitted to a fundus camera (Carl Zeiss Meditec, Jena, Germany) (Figure 2) [11]. In ‘static vessel analysis’, a single fundus picture is used to measure arterial and venous vessel diameters around the optic nerve and calculate the central arterial equivalent, the central retinal venous equivalent and the arterial-to-venous diameter ratio (AVR) [12]. Large epidemiological studies showed evidence that these values are indicators for cardioand cerebrovascular events [13]. In ‘dynamic vessel analysis’, the instrument measures vessel diameter in relation to time and local position along a vessel in real time continuously 25 times per second. The examination of function and individual capacities of vessel segments along the vessel is based on the fact that the vessel diameters are the essential adjusting elements of autoregulation. As an additional stimulation test for vessel function, the DVA interrupts the green measuring light and generates a flicker light with a frequency of 12.5 Hz with a bright-to-dark ratio of 25:1. The diameter responses can be recorded, and the dilation of vessel diameter is used as a functional diagnostic parameter for the endotheliumderived vasodilation. Since autoregulation is a generic term for different local feedback control systems, superimposed on each other vessel behaviour ranges from dynamic vessel changes within seconds (flicker response) to minutes (metabolic response). Although a general outline of the circulation and its autoregulation is useful for haemodynamic purposes, special circulations exist to meet the functional needs of individual organs. In many diseases, the kidney and the eye are linked—only recently in this journal, an editorial comment reviewed the linkage between dense-deposit disease and retinal drusen [14]. In type 1 and type 2 diabetes, patients