Response Of Retinal Vessels Research Articles

Retinal Vessel Functional Responses in South Africans Living With and Without HIV: The EndoAfrica-NWU Study.

The effects of HIV and antiretroviral therapy (ART) on microvascular function are poorly explored. We compared retinal vessel functional responses to flicker light-induced provocation (FLIP) in people living with HIV (PLWH) and people living without HIV (PLWoutH). We included 115 PLWH and 51 PLWoutH with a median age of 41 years. Treated PLWH received similar first-line fixed-dose combination ART. Clinical characteristics and retinal vessels functional responses to FLIP were compared in (a) PLWH and PLWoutH; and (b) PLWH groups stratified by the median of (i) CD4-count (511 cells/mm3), (ii) viral load (50 copies/mL), and (iii) ART duration (57.6 months). PLWH were older, smoked more, and had a lower prevalence of hypertension than PLWoutH (p < 0.05). Almost 64% of PLWH were infected for more than 5 years. Retinal vessel responses to FLIP were similar between PLWH and PLWoutH after taking confounders into account. In addition, PLWH subgroups stratified according to immuno-virological status by CD4-count, viral load, and ART duration showed no differences in retinal vessel responses to FLIP. Living with HIV and receiving ART were not associated with altered microvascular function as assessed with dynamic retinal vessel analysis in a South African case-control study.

Retinal vascular dynamics: A window for observing an irregular heartbeat. A case report.

We aimed to characterize several aspects of retinal vascular dynamics in a patient with arrythmia in order to elicit additional diagnostic information on microvascular dysfunction. A 68-year-old male patient with arrythmia and an age- and gender-matched control subject underwent ocular examination including dynamic retinal vessel assessment with flicker light provocation. Retinal vessel diameters were measured continuously following a standard protocol (IMEDOS Systems, Jena, Germany). The data were evaluated using methods of signal analysis. Retinal vessel response following flicker provocation as well as local structural and functional behavior of retinal vessels were comparable between both individuals. The arrhythmia case demonstrated irregular arterial and venous heart rate (HR) pulsation with an average frequency of 1Hz. Moreover, the case showed a higher magnitude and larger periods of low-frequency retinal vessel oscillations as well as lower periodicity of both HR pulsations and low-frequency vasomotions. Besides numerical examination of irregular HR pulsations in case of arrhythmia, from the direct noninvasive assessment of retinal vessel dynamics one can derive more detailed information on microvascular function including the whole spectrum of retinal arterial and venous pulsations and vasomotions. This may have implications for health screening not limited to atrial fibrillation.

Automated Retinal Vessel Analysis Based on Fundus Photographs as a Predictor for Non-Ophthalmic Diseases-Evolution and Perspectives.

The study of retinal vessels in relation to cardiovascular risk has a long history. The advent of a dedicated tool based on digital imaging, i.e., the retinal vessel analyzer, and also other software such as Integrative Vessel Analysis (IVAN), Singapore I Vessel Assessment (SIVA), and Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE), has led to the accumulation of a formidable body of evidence regarding the prognostic value of retinal vessel analysis (RVA) for cardiovascular and cerebrovascular disease (including arterial hypertension in children). There is also the potential to monitor the response of retinal vessels to therapies such as physical activity or bariatric surgery. The dynamic vessel analyzer (DVA) remains a unique way of studying neurovascular coupling, helping to understand the pathogenesis of cerebrovascular and neurodegenerative conditions and also being complementary to techniques that measure macrovascular dysfunction. Beyond cardiovascular disease, retinal vessel analysis has shown associations with and prognostic value for neurological conditions, inflammation, kidney function, and respiratory disease. Artificial intelligence (AI) (represented by algorithms such as QUantitative Analysis of Retinal vessel Topology and siZe (QUARTZ), SIVA-DLS (SIVA-deep learning system), and many others) seems efficient in extracting information from fundus photographs, providing prognoses of various general conditions with unprecedented predictive value. The future challenges will be integrating RVA and other qualitative and quantitative risk factors in a unique, comprehensive prediction tool, certainly powered by AI, while building the much-needed acceptance for such an approach inside the medical community and reducing the "black box" effect, possibly by means of saliency maps.

Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca v 2.3-Deficient Mice-An in-vivo Evaluation Using Retinal Vessel Analysis (RVA).

Objective: Metabolic demand increases with neuronal activity and adequate energy supply is ensured by neurovascular coupling (NVC). Impairments of NVC have been reported in the context of several diseases and may correlate with disease severity and outcome. Voltage-gated Ca2+-channels (VGCCs) are involved in the regulation of vasomotor tone. In the present study, we compared arterial and venous responses to flicker stimulation in Cav2.3-competent (Cav2.3[+/+]) and -deficient (Cav2.3[−/−]) mice using retinal vessel analysis.Methods: The mice were anesthetized and the pupil of one eye was dilated by application of a mydriaticum. An adapted prototype of retinal vessel analyzer was used to perform dynamic retinal vessel analysis. Arterial and venous responses were quantified in terms of the area under the curve (AUCart/AUCven) during flicker application, mean maximum dilation (mMDart/mMDven) and time to maximum dilation (tMDart/tMDven) during the flicker, dilation at flicker cessation (DFCart/DFCven), mean maximum constriction (mMCart/mMCven), time to maximum constriction (tMCart/tMCven) after the flicker and reactive magnitude (RMart/RMven).Results: A total of 33 retinal scans were conducted in 22 Cav2.3[+/+] and 11 Cav2.3[−/−] mice. Cav2.3[−/−] mice were characterized by attenuated and partially reversed arterial and venous responses, as reflected in significantly lower AUCart (p = 0.031) and AUCven (p = 0.047), a trend toward reduced DFCart (p = 0.100), DFCven (p = 0.100), mMDven (p = 0.075), and RMart (p = 0.090) and a trend toward increased tMDart (p = 0.096).Conclusion: To our knowledge, this is the first study using a novel, non-invasive analysis technique to document impairment of retinal vessel responses in VGCC-deficient mice. We propose that Cav2.3 channels could be involved in NVC and may contribute to the impairment of vasomotor responses under pathophysiological conditions.

L-Citrulline ameliorates the attenuation of acetylcholine-induced vasodilation of retinal arterioles in diabetic rats

In our previous study, we found that the vasodilation of retinal arterioles induced by acetylcholine and BMS-191011, a large-conductance Ca2+-activated K+ (BKCa) channel opener, were diminished in diabetic rats. Currently, few agents ameliorate the impaired vasodilator responses of retinal blood vessels. Our recent finding that the intravenous infusion of L-citrulline dilated retinal arterioles, suggests that L-citrulline could be a potential therapeutic agent for circulatory disorders of the retina. In this study, we determined the effect of an oral L-citrulline treatment on impaired acetylcholine- and BMS-191011-induced vasodilation in the retinal arterioles of diabetic rats. To induce diabetes, rats were administered an intravenous dose of streptozotocin (65 mg/kg) and a 5% D-glucose solution as drinking water. The L-citrulline (2 g/kg/day) and L-arginine (2 g/kg/day) treatments commenced either 15 days before or just after the streptozotocin injection and continued throughout the experimental period. A 29-day treatment with L-citrulline, but not L-arginine, significantly ameliorated the impaired acetylcholine- and BMS-191011-induced retinal vasodilation in diabetic rats without affecting their plasma glucose levels. The 2-week L-citrulline treatment tended to ameliorate the dysfunction of the acetylcholine-induced retinal vasodilation in diabetic rats. In conclusion, these results showed that the retinal blood vessel dysfunction induced by diabetes mellitus could be prevented by the long-term administration of L-citrulline and suggest that the latter could play a potentially prophylactic role in diabetic retinopathy.

Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.

Low or high sympatho-adrenal-medullary axis (SAM) and hypothalamic-pituitary-adrenal axis (HPA) dysregulation reflect chronic stress. Retinal vessel dynamics may relate to SAM, HPA activity and stroke risk. Our objectives were therefore to assess the relationships between retinal vessel, SAM and HPA responses, and to determine stroke risk. A prospective bi-ethnic gender cohort (n = 275, 45 ± 9 years) was included. Urine/serum/saliva samples for SAM [norepinephrine:creatinine ratio (u-NE)] and HPA [adrenocorticotrophic hormone (ACTH), cortisol] were obtained at baseline, three-year follow up and upon flicker light-induced provocation. Diastolic ocular perfusion pressure was measured as a marker of hypo-perfusion. Retinal arterial narrowing and venous widening calibres were quantified from digital images in the mydriatic eye. A validated stress and stroke risk score was applied. An interaction term was fitted for venous dilation in u-NE tertiles (p ≤ 0.05) and not in u-NE median/quartiles/quintiles. Independent of race or gender, tertile 1 (low u-NE) had a 112% increase in u-NE, decreases in cortisol, and no changes in ACTH over three years (positive feedback). Tertile 3 (high u-NE) contradictorily had decreases in u-NE and cortisol, and increases in ACTH (negative feedback). In tertile 1, reduced arterial dilation, and faster arterial vasoconstriction and narrowing were related to higher SAM activity and hypo-perfusion (p ≤ 0.05), whereas delayed venous dilation, recovery and widening were related to cortisol hypo-secretion (p ≤ 0.05). In tertile 1, delayed venous recovery responses predicted stress and stroke risk [odds ratio 4.8 (1.2-19.6); p = 0.03]. These associations were not found in u-NE tertiles 2 and 3. In response to low norepinephrine, a reflex increase in SAM activity occurred, enhancing arterial vasoconstriction and hypo-perfusion. Concomitant HPA dysregulation attenuated retinal vein vasoactivity and tone, reflecting delayed vein recovery responses and non-adaptation to stress. These constrained vein recovery responses are indicative of increased chronic stress and stroke risk.

Altered cerebral vessel amplitude and oscillation frequencies in Alzheimer’s disease compatible with impaired amyloid clearance

AbstractBackgroundRetinal vessels are similar to cerebral vessels in their structure and function. Using a non‐invasive in‐vivo technique, we demonstrated previously that retinal vessel response to flicker is more emphasized and delayed in patients with dementia due to Alzheimer’s disease (AD) compared to healthy controls (HC). Increasing evidence suggests that interstitial fluid of gray matter appears to flow outward via paravascular spaces which are located alongside cerebral vessels possibly being passively propulsed by vessels’ pulsatility. Impaired pulsatility resulting in impaired clearance of molecules such as beta‐amyloid may in parts explain amyloid deposition in the brain. Moderate low pulsatility frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in mice just recently. We aimed to elucidate whether retinal vessels’ pulsatility in particular at low frequencies (0.05‐0.15 Hz) is changed in AD at the stage of dementia or mild cognitive impairment (MCI).MethodsThree groups of participants were examined by Dynamic Vessel Analyzer (IMEDOS Systems): 17 patients, 72.0 (62.0 – 79.0) y.o. [median (1st quartile – 3rd quartile)], with mild‐to‐moderate dementia due to probable AD ; 23 patients, 69.0 (61.0 – 71.0) y.o. with MCI due to AD, and 18 anamnestic healthy control subjects 66.5 (61.3 – 66.5) y.o. without cognitive impairment (HC).ResultsPower spectra of the temporal arterial curves differed between the groups. Especially at moderate low frequencies around 0.1 Hz (0.05 – 0.15 Hz) ADD and most MCI arterial oscillations, characterized by the normalized area under the power spectrum, prevailed over HC oscillations. Within the heart frequency range of 0.8 – 0.9 Hz retinal arterial pulsations in MCI and AD groups were significantly more emphasized as in the HC group.ConclusionsIn ADD and MCI power spectra of retinal arterial oscillations seem to shift from very low to moderate low frequencies. Interestingly, the latter frequencies correspond to those reported for lymphatic vessels in humans and those for paravascular drainage in mice. The emphasized retinal arterial pulsation at moderate low frequencies in ADD and MCI group would be compatible with the view of compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.

Leptin and the Retinal Microvasculature in Young Black and White Adults: The African-PREDICT Study

Leptin is a vasoactive peptide that has been linked to diseases associated with macrovascular deterioration. What is still uncertain is its involvement in the microvasculature. Since microvascular changes are presumed to precede macrovascular deterioration, we examined whether measures of the retinal microvasculature are associated with leptin in healthy, young Black and White individuals. We included 283 Black and 289 White men and women (aged 20-30 years). We determined serum leptin, calculated central retinal artery and vein equivalents and arterio-venous ratio. We also measured retinal vessel responses to light flicker provocation. Black men were leaner and had lower leptin than White men, whereas Black women had increased adiposity and leptin compared to White women (all p<0.001). Black groups had narrower retinal arteries, and greater maximum arteriolar and venular dilations in response to light flicker than the White groups (p<0.001). Arterio-venous ratio associated negatively with leptin (all p≤0.044) in all groups (except Black women), but was lost upon adjustment for body mass index and other covariates. We found an inverse association between maximal venular dilation and leptin only in Black men in single and multiple regression analyses (Std β= -0.22; R2=0.05; p=0.035). No associations were found between other retinal measures with leptin in the other groups. We found an independent, negative association between retinal vein dilation with leptin in healthy, young Black men, suggesting a potential detrimental role for leptin in regulating microvascular responses in a population group known to be at greater risk of cardiovascular disease development.

未熟児網膜症モデルラットにおいて内皮依存性網膜血管拡張反応が減弱する

未熟児網膜症モデルラットにおいて内皮依存性網膜血管拡張反応が減弱する

Serum Phosphate and Microvascular Function in a Population-Based Cohort.

Higher serum phosphate is associated with cardiovascular events and all-cause mortality. Explanations of this association have focused on large vessel calcification and stiffness. Studies suggest that a higher serum phosphate induces microvascular dysfunction, but relationships in humans with direct measures of microvascular function are lacking. We performed a cross-sectional analysis of 3189 community-living participants that underwent skin capillaroscopy, laser-Doppler flowmetry, and flicker light-induced retinal vessel responses. We used linear regression to assess the association between serum phosphate and each microvascular outcome. The primary outcome was skin capillary recruitment during postocclusive peak reactive hyperemia by capillaroscopy. Secondary outcomes included capillary recruitment during venous congestion, heat-induced skin hyperemic response, flicker light-induced retinal arteriolar, and venular dilation. The mean age of the cohort was 59±8 years, 48% were women, 7% had an eGFR <60 ml/min per 1.73 m2, and the mean serum phosphate concentration was 3.2±0.5 mg/dl. A 1 mg/dl higher serum phosphate was independently associated with a 5.0% lower postocclusive capillary recruitment (95% CI, -10.0% to -0.1%). Results were similar for capillary recruitment with venous congestion (-4.5%; 95% CI, -9.8% to 0.7%). A 1 mg/dl higher serum phosphate was also independently associated with a 0.23% lower retinal venular dilation in response to flicker light (95% CI, -0.44% to -0.02%). A higher serum phosphate was not associated with change in flicker light-induced retinal arteriolar dilation or heat-induced skin hyperemic response, however a higher serum phosphate was associated with a lower heat-induced skin hyperemic response among men (-149% [95% CI, -260 to -38] per 1 mg/dl higher serum phosphate) but not women (P interaction, 0.01). Higher serum phosphate concentrations, even within the normal range, are associated with microvascular dysfunction in community-living individuals. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_20_CJN02610319.mp3.

Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis.

BackgroundImpairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC.MethodsA prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed.ResultsA total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001).ConclusionsTo the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals.

The relationship of systemic markers of haemostasis with retinal blood vessel responses in cardiovascular disease and/or diabetes

Background Hypercoagulability is a leading factor in diabetes and cardiovascular disease. Retinal vessel responses to flickering light are an important tool for assessing ocular function. We hypothesised a significant relationship between systemic markers of haemostasis and retinal vessel function.Methods Intra-ocular pressure and retinal microcirculation function were measured in 116 patients with diabetes and/or cardiovascular disease using unstimulated and stimulated arterial and venous retinal vessel responses to flickering light. Haemostasis was evaluated by platelet microparticles, soluble P selectin, and five functional markers of fibrin clot formation and lysis, hyperglycaemia by HbA1c.Results Intra-ocular pressure was linked to the rates of clot formation (p = 0.006) and clot dissolution (p = 0.013) whilst central retinal vein equivalent was linked to HbA1c (p = 0.017). In the first of three flickering light cycles only, arterial baseline diameter fluctuation was linked to the lag time to clot formation (p = 0.017), whilst maximum venous dilatation was linked to HbA1c (p = 0.001) and clot density (p = 0.011). HbA1c was linked to venous dilatation amplitude (p = 0.003). There were no significant links between any ocular index and any platelet index.Conclusions In addition to glycaemia, several haemostasis measures, but no measures of platelet activity, are linked to ocular and retinal blood vessel indices in patients with diabetes and/or cardiovascular disease. These associations may have pathophysiological significance.

Hypoxia challenge test and retinal circulation changes - a study using ocular coherence tomography angiography.

Previous studies report that the response of retinal vessels to a decrease in oxygen (hypoxia) is vasodilation, thus increasing blood flow. We aimed to characterize the changes in retinal microvasculature induced by a mild hypoxia stress test in a healthy population, using ocular coherence tomography angiography (OCT-A) technology. Interventional repeated-measures study. The standardized hypoxia challenge test (HCT) was performed to all volunteers, according to the BritishThoracic Society protocol. Ocular coherence tomography angiography (OCT-A) was performed at three time-points (baseline, during HCT and 30' posthypoxia). Macular and peripapillary vessel densities were assessedusing the built-in software. To minimize bias, analysis was performed separately in right (OD) and left (OS) eyes. Repeated-measures anova and mean comparison analysis were used as statistical tests (stata v13). Studied population included 30 healthy subjects (14 women), with a mean age of 28.8±4.2 [range 22-37] years. Baseline vessel density increased in hypoxic conditions and subsequently decreased to near-baseline values in posthypoxia conditions. This pattern was observed for both eyes in both parafovea (OD: 55.3±2.3 to 56.7±1.9 to 55.8±1.9, p<0.05; OS: 56.9±2.1 to 57.9±1.9 to 57.3±1.7, p<0.05) and peripapillary (OD: 60.5±0.5 to 62.6±0.5 to 60.1±0.4, p<0.05; OS: 60.4±0.4 to 62.3±0.5 to 60.7±0.4, p<0.05) areas. To our knowledge, there are no published data specifically addressing mild hypoxia conditions and retinal microvasculature changes, using OCT-A. This pilot study may pave way to better understand vascular responses in disease setting.

Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer\u2019s disease

Neurovascular coupling can be directly assessed by retinal vessel response to flickering light using optical imaging methods. The response is altered in a number of ocular and cardiovascular diseases. Whether it is altered in Alzheimer’s disease (AD) is investigated. Retinal vessel reaction to monochromatic flicker stimulation was examined by Dynamic Vessel Analyzer independent of the commercial software in elderly subjects: 15 patients with mild-to-moderate dementia due to AD (ADD); 24 patients with mild cognitive impairment due to AD (MCI); 15 cognitively healthy controls (HC). Retinal vessels in ADD showed a more emphasized and delayed reactive dilation as compared to HC. In MCI, these aspects still differed from those seen in ADD. Maximal arterial reaction was increased and dilation was delayed in ADD as compared to HC (p = 0.004 and p < 0.001) and to MCI (p = 0.058 and p = 0.004), respectively. Maximal venous reaction was increased in ADD as compared to HC (p = 0.001) and to MCI (p = 0.007), respectively. This finding suggests that retinal neuronal activity is either increased or feed-back loop of neurovascular coupling is damaged with differentiating alterations across the spectrum of AD. Thus, retinal vessel reaction to flicker stimulation is considered a promising non-invasive, widely available and easy-to-administer future biomarker for the diagnosis and monitoring of AD.

Remote ischemia affects the diameter of larger retinal vessels in normal persons

PurposeRemote ischemic conditioning (RIC) implies that repeated episodes of ischemia in one organ can protect another remote organ from the adverse consequences of ischemia. It remains to be elucidated whether the diameter response in retinal vessels can be used as a marker of RIC in general and whether the response can be used to predict the effect of RIC on the visual prognosis in diseases characterized by retinal ischemia.MethodsIn twenty normal persons aged 20–31 years the Dynamic Vessel Analyzer (DVA) was used to measure the resting diameter and diameter changes during isometric exercise and flicker stimulation before, immediately after, and one hour after RIC induced by transient ischemia in the left arm.ResultsThe baseline diameter of retinal venules was reduced non‐significantly immediately after (p = 0.07) and significantly one hour after RIC (p &lt; 0.009), whereas the baseline diameter of arterioles was unaffected by the intervention (p &gt; 0.61). Arterial constriction induced by isometric exercise was significantly reduced immediately after RIC (p &lt; 0.04), but not one hour after RIC (p &gt; 0.99). None of the other diameter responsese were affected by RIC (p &gt; 0.22 for all comparisons).ConclusionsThe diameter of large retinal vessels is affected one hour after controlled transient ischemia in the left arm. This indicates that the diameter response of retinal vessels could be a potential marker of ischemic conditioning in the body in general. The potential of remote ischemic conditioning as an intervention on vision threatening retinal diseases where ischemia is a part of the pathogenesis should be investigated.

ALTERED CEREBRAL VESSEL OSCILLATION FREQUENCIES AS A POSSIBLE CAUSE OF IMPAIRED AMYLOID CLEARANCE

Retinal vessels are similar to cerebral vessels in their structure and function. Using a non-invasive in-vivo technique, we demonstrated previously that retinal vessel response to flicker is altered in Alzheimer's disease (AD): patients with dementia due to AD (ADD) showed more emphasized and delayed reactive dilation. Interstitial fluid of gray matter appears to flow outward via perivascular spaces which are located alongside cerebral vessels being passively propulsed by vessels’ pulsatility. Impaired pulsatility resulting in impaired clearance may in part explain amyloid deposition in the brain. We aimed to elucidate whether retinal vessels’ pulsatility is changed an ADD or mild cognitive impairment (MCI). Three groups of participants were examined by Dynamic Vessel Analyzer (IMEDOS Systems): 11 patients, 76.2 (72.5 − 80.0) y.o. [median (1st. quartile − 3rd quartile)], with mild-to-moderate dementia due to probable AD fulfilling the standard diagnostic criteria (ADD); 20 patients, 69.2 (63.6 − 72.0) y.o. with mild cognitive impairment (MCI) due to AD, and 14 anamnestic healthy control subjects 67.1 (58.5 − 70.8) y.o. without cognitive impairment (HC). Oscillatory temporal changes of retinal vessel diameters were assessed during 40 s and were evaluated using mathematical signal analysis. The relative to the vessel diameter magnitude of arterial oscillations was higher in ADD. Power spectra of the temporal curves differed between the groups especially within low frequency range of 0 − 0.2 Hz. In arteries at very low frequencies < 0.05 Hz HC oscillations, characterized by the normalized area under the power spectrum, prevailed over ADD and MCI oscillations. At moderate low frequencies (0.05 − 0.2 Hz) ADD and most MCI oscillations prevailed over HC oscillations. In ADD and MCI power spectra shifted from very low to moderate low frequencies. Interestingly, the latter frequencies correspond to those reported for lymphatic vessels. The emphasized retinal arterial pulsation at moderate low frequencies in ADD and MCI group would be compatible with the view of compensatory upregulation in AD and strengthen the amyloid clearance hypothesis.

Dynamic Responses in Retinal Vessel Caliber With Flicker Light Stimulation and Risk of Diabetic Retinopathy and Its Progression.

This study investigated the associations between the responses of retinal vessels to flickering light and the incidence and progression of diabetic retinopathy (DR). A prospective cohort study of adult subjects with diabetes mellitus. The dynamic vessel analyser (DVA) was used to measure retinal vascular dilatation in response to diffuse illuminance flicker. Diabetic retinopathy was graded from retinal photography at baseline and at 1 year. Incident DR and two-step change in DR were analyzed. There were 276 subjects in total, with a mean age of 59.8 ± 8.9 years. The majority were male (73%) and the mean glycated hemoglobin A1c (HbA1c) level and mean duration of diabetes were 7.7 ± 1.4% and 14.0 ± 10.5 years, respectively. After adjustments for age, sex, smoking, duration of diabetes, HbA1c, hypertension, and hyperlipidemia, the responses of retinal arterioles to flicker stimulation were lower in subjects with incident DR (P = 0.048). Subjects with greater arteriolar dilatory responses were less likely to have DR progression (odds ratio [OR] 1.85, [95% confidence interval [CI] 1.33-2.56], P = 0.012, per SD decrease). Subjects with greater venular dilatory responses were also less likely to have DR progression (OR 1.89, [95% CI 1.35-2.63], P = 0.003, per SD decrease). There were no significant associations between arteriolar or venular dilation response and incident proliferative DR (PDR) and DR regression. Reduced retinal arteriolar and venular dilatory responses to flickering light are associated with risk of DR progression at 1 year in adult patients with diabetes.

Differential effects of nitric oxide and cyclo-oxygenase inhibition on the diameter of porcine retinal vessels with different caliber during hypoxia ex vivo

BackgroundHypoxia induced relaxation of larger retinal arterioles has been shown to be mediated by nitric oxide (NO) and cyclo-oxygenase (COX) products both in vivo and in vitro. However, the involvement of smaller retinal vessels in the response is unknown. Therefore, the purpose of the present study was to investigate the effect of blocking the synthesis of NO and COX on hypoxia induced changes in the diameter of smaller porcine retinal vessels at different branching level. MethodsPorcine hemiretinas were mounted in a tissue chamber and were constricted with the prostaglandin agonist U46619. Changes in the diameter of arterioles, pre-capillary arterioles and capillaries were studied during hypoxia, in the presence of the COX inhibitor ibuprofen and the NO synthase inhibitor L-NAME. ResultsIn the presence of L-NAME hypoxia induced dilatation was significantly smaller in arterioles and capillaries than in precapillary arterioles (p < 0.04), whereas in the presence of ibuprofen the dilatation was significantly smaller in capillaries and pre-capillary arterioles than in arterioles (p < 0.04). ConclusionsThe mechanisms underlying hypoxia induced dilatation differ among smaller porcine retinal vessels with different caliber ex vivo. This may reflect differences in the responses of retinal vessels to changes in metabolism, and may point to possible targets for pharmacological intervention on the diameter of retinal vessels with different caliber in vivo.

Retinal vessel responses to flickering light provocation in a cohort of black and white teachers: the SABPA study

Retinal vessel responses to flickering light provocation in a cohort of black and white teachers: the SABPA study

Anodal direct current stimulation at the eye evokes temporary variations in retinal vessel response to flicker

Stefanie Freitag, Alexander Hunold, Matthias Klemm, Sascha Klee, Steffen Rieger, Dietmar Link, Jens Haueisen