Diameter Of Retinal Blood Vessels Research Articles

Sitagliptin eye drops prevent the impairment of retinal neurovascular unit in the new Trpv2+/− rat model

Impaired function of the retinal neurovascular unit (NVU) is an early event in diabetic retinopathy (DR). It has been previously shown that topical delivery of the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin can protect against diabetes-mediated dysfunction of the retinal NVU in the db/db mouse. The aim of the present study was to examine whether sitagliptin could prevent the DR-like lesions within the NVU of the new non-diabetic model of DR, the Trpv2 knockout rat (Trpv2+/−). For that purpose, at 3 months of age, Trpv2+/− rats were topically treated twice daily for two weeks with sitagliptin or PBS-vehicle eyedrops. Trpv2+/+ rats treated with vehicle served as the control group. Body weight and glycemia were monitored. Optical coherence tomography recordings, fundus images and retinal samples were obtained to evaluate sitagliptin effects. The results revealed that sitagliptin eye drops had no effect on body weight or glycemia. Vehicle-treated Trpv2+/− rats exhibited retinal thinning and larger diameters of major retinal blood vessels, upregulation of inflammatory factors and oxidative markers, glial activation and formation of acellular capillaries. However, topical administration of sitagliptin significantly prevented all these abnormalities. In conclusion, sitagliptin eye drops exert a protective effect against DR-like lesions in Trpv2+/− rats. Our results suggest that sitagliptin eye drops carry significant potential to treat not only early-stages of DR but also other diseases with impairment of the NVU unrelated to diabetes.

Retinal blood vessel diameter changes with 60-day head-down bedrest are unaffected by antioxidant nutritional cocktail

Long-term human spaceflight can lead to cardiovascular deconditioning, but little is known about how weightlessness affects microcirculation. In this study, we examined how the retinal microvessels and cerebrovascular regulation of 19 healthy male participants responded to long-term head-down bedrest (HDBR), an earth-based analog for weightlessness. In addition, we examined whether an anti-inflammatory/antioxidant cocktail could prevent the vascular changes caused by HDBR. In all study participants, we found a decrease in retinal arteriolar diameter by HDBR day 8 and an increase in retinal venular diameter by HDBR day 16. Concurrently, blood pressure at the level of the middle cerebral artery and the cerebrovascular resistance index were higher during HDBR, while cerebral blood flow velocity was lower. None of these changes were reversed in participants receiving the anti-inflammatory/antioxidant cocktail, indicating that this cocktail was insufficient to restore the microvascular and cerebral blood flow changes induced by HDBR.

Retinal Blood Vessel Tracking and Diameter Estimation via Gaussian Process With Rider Optimization Algorithm.

Retinal blood vessels structure analysis is an important step in the detection of ocular diseases such as diabetic retinopathy and retinopathy of prematurity. Accurate tracking and estimation of retinal blood vessels in terms of their diameter remains a major challenge in retinal structure analysis. In this research, we develop a rider-based Gaussian approach for accurate tracking and diameter estimation of retinal blood vessels. The diameter and curvature of the blood vessel are assumed as the Gaussian processes. The features are determined for training the Gaussian process using Radon transform. The kernel hyperparameter of Gaussian processes is optimized using Rider Optimization Algorithm for evaluating the direction of the vessel. Multiple Gaussian processes are used for detecting the bifurcations and the difference in the prediction direction is quantified. The performance of the proposed Rider-based Gaussian process is evaluated with mean and standard deviation. Our method achieved high performance with the standard deviation of 0.2499 and mean average of 0.0147, which outperformed the state-of-the-art method by 6.32%. Although the proposed model outperformed the state-of-the-art method in normal blood vessels, in future research, one can include tortuous blood vessels of different retinopathy patients, which would be more challenging due to large angle variations. We used Rider-based Gaussian process for tracking blood vessels to obtain the diameter of retinal blood vessels, and the method performed well on the "STrutred Analysis of the REtina (STARE) Database" accessed on Oct. 2020 (https://cecas.clemson.edu/~ahoover/stare/). To the best of our knowledge, this experiment is one of the most recent analysis using this type of algorithm.

Retinal blood vessel diameters in children and adults exposed to a simulated altitude of 3,000m.

Introduction: Technological advances have made high-altitude ski slopes easily accessible to skiers of all ages. However, research on the effects of hypoxia experienced during excursions to such altitudes on physiological systems, including the ocular system, in children is scarce. Retinal vessels are embryologically of the same origin as vessels in the brain, and have similar anatomical and physiological characteristics. Thus, any hypoxia-related changes in the morphology of the former may reflect the status of the latter. Objective: To compare the effect of one-day hypoxic exposure, equivalent to the elevation of high-altitude ski resorts in North America and Europe (∼3,000m), on retinal vessel diameter between adults and children. Methods: 11 adults (age: 40.1 ± 4.1years) and 8 children (age: 9.3 ± 1.3years) took part in the study. They spent 3days at the Olympic Sports Centre Planica (Slovenia; altitude: 940m). During days 1 and 2 they were exposed to normoxia (FiO2 = 0.209), and day 3 to normobaric hypoxia (FiO2 = 0.162 ± 0.03). Digital high-resolution retinal fundus photographs were obtained in normoxia (Day 2) and hypoxia (Day 3). Central retinal arteriolar equivalent (CRAE) and venular equivalents (CRVE) were determined using an Automated Retinal Image Analyser. Results: Central retinal arteriolar and venular equivalents increased with hypoxia in children (central retinal arteriolar equivalent: 105.32 ± 7.72µm, hypoxia: 110.13 ± 7.16µm, central retinal venular equivalent: normoxia: 123.39 ± 8.34µm, hypoxia: 130.11 ± 8.54µm) and adults (central retinal arteriolar equivalent: normoxia: 105.35 ± 10.67µm, hypoxia: 110.77 ± 8.36µm; central retinal venular equivalent: normoxia: 126.89 ± 7.24µm, hypoxia: 132.03 ± 9.72µm), with no main effect of group or group*condition interaction. A main effect of condition on central retinal arteriolar and venular equivalents was observed (central retinal arteriolar equivalent:normoxia: 105.34 ± 9.30µm, hypoxia: 110.50 ± 7.67µm, p < 0.001; central retinal venular equivalent: normoxia: 125.41 ± 7.70µm, hypoxia: 131.22 ± 9.05µm, p < 0.001). Conclusion: A 20-hour hypoxic exposure significantly increased central retinal arteriolar and venular equivalents in adults and children. These hypoxia-induced increases were not significantly different between the age groups, confirming that vasomotor sensitivity of the retinal vessels to acute hypoxia is comparable between adults and prepubertal children.

Methods to measure blood flow and vascular reactivity in the retina.

Disturbances of retinal perfusion are involved in the onset and maintenance of several ocular diseases, including diabetic retinopathy, glaucoma, and retinal vascular occlusion. Hence, knowledge on ocular vascular anatomy and function is highly relevant for basic research studies and for clinical judgment and treatment. The retinal vasculature is composed of the superficial, intermediate, and deep vascular layer. Detection of changes in blood flow and vascular diameter especially in smaller vessels is essential to understand and to analyze vascular diseases. Several methods to evaluate blood flow regulation in the retina have been described so far, but no gold standard has been established. For highly reliable assessment of retinal blood flow, exact determination of vessel diameter is necessary. Several measurement methods have already been reported in humans. But for further analysis of retinal vascular diseases, studies in laboratory animals, including genetically modified mice, are important. As for mice, the small vessel size is challenging requiring devices with high optic resolution. In this review, we recapitulate different methods for retinal blood flow and vessel diameter measurement. Moreover, studies in humans and in experimental animals are described.

Multi-modal retinal scanning to measure retinal thickness and peripheral blood vessels in multiple sclerosis

Our purpose was to investigate changes to the retina in multiple sclerosis (MS) using established and novel modes of retinal image acquisition and analysis. 72 participants with MS and 80 healthy volunteers underwent retinal scanning with optical coherence tomography (OCT) and ultra-widefield (UWF) scanning laser ophthalmoscopy (SLO), over a two-year period. Changes in retinal nerve fibre layer (RNFL) thickness, macular volume and retinal blood vessel diameter were measured and parameters were then tested for associations with MS. Measurements from OCT showed that individuals with MS had a thinner RNFL and reduced macular volume when compared to healthy volunteers. On UWF images, participants with MS had reduced arterial widths in the inferior nasal quadrant of both eyes and reduced venous widths in the inferior nasal quadrant of right eyes. Longitudinal analysis showed that participants with MS had an accelerated annual rate of RNFL thinning in several regions of the retina. In conclusion, the assessment of OCT showed thinning of the RNFL and macula in concordance with previous reports on MS, while analysis of blood vessels in the retinal periphery from UWF-SLO images revealed novel changes.

Exploring Retinal Blood Vessel Diameters as Biomarkers in Multiple Sclerosis.

We aimed to determine whether retinal vessel diameters and retinal oxygen saturation in newly diagnosed patients with multiple sclerosis (pwMS) are different from those of a healthy population. Retinal blood vessel diameters were measured using imaging with a spectrophotometric non-invasive retinal oximeter. Twenty-three newly diagnosed untreated relapsing-remitting MS (RRMS) patients (mean age: 32.2 ± 7.5 years, age range = 18–50 years, 56.5% female) were measured and compared to 23 age- and sex-matched healthy controls (HCs) (mean age: 34.8 ± 8.1 years). Patients with Optic Neuritis were excluded. Retinal venular diameter (143.8 µm versus 157.8 µm: mean; p = 0.0013) and retinal arteriolar diameter (112.6 µm versus 120.6 µm: mean; p = 0.0089) were smaller in pwMS when compared with HCs, respectively. There was no significant difference in the oxygen saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively. There was a significant difference in the median low contrast visual acuity (2.5% contrast) between the pwMS and the HC groups (p = 0.0143) Retinal arteriolar and venular diameter may have potential as objective biomarkers for MS.

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

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

Associations Between Outdoor Air Pollution and the Retinal Microvasculature in School-aged Children in a Region Impacted by Residential Biomass Burning

BACKGROUND AND AIM: Disruptions to the microcirculation may be an important pathway by which fine particulate air pollution (PM2.5) and oxidant gases contribute to cardiovascular disease. To date, little is known about the early-life cardiovascular health impacts of air pollution. This study aimed to evaluate associations between outdoor air pollution (PM2.5 and oxidant gases) and retinal blood vessel diameter (a measure of microvascular health) in children living in a region impacted by residential biomass burning. METHODS: In this repeated-measures panel study in rural British Columbia, Canada, a median of 6 retinal vessel measurements were collected from 64 children (ages 4-12 years), for a total of 344 retinal measurements. Daily mean PM2.5, nitrogen dioxide (NO2) and ozone (O3) were measured, and the combined oxidant capacity of NO2 and O3 was calculated using a redox-weighted average (Ox). Linear mixed-effect models with a random subject intercept were used to estimate associations between PM2.5 or Ox (same-day, 3-day, 7-day, and 21-day means) and the diameter of retinal arterioles and venules, adjusting for confounding variables. Models with an interaction term between PM2.5 and Ox were also run to assess whether associations between PM2.5 and retinal vessel diameter were modified by Ox. RESULTS:Ox was inversely associated with retinal arteriolar diameter, with the strongest association observed for 7-day mean exposures: each 10 ppb increase in Ox was associated with a 2.63 μm decrease in arteriolar diameter (95% confidence interval: -4.63, -0.63). Moreover, Ox modified associations between PM2.5 and arteriolar diameter, with weak inverse associations observed between PM2.5 and arteriolar diameter only at higher concentrations of Ox. CONCLUSIONS:Our results suggest that outdoor air pollution has a measurable impact on the microvasculature of children. Moreover, our findings indicate that interactions between PM2.5 and Ox may play a role in determining the magnitude and direction of these associations. KEYWORDS: children's environmental health, particulate matter, ozone, cardiovascular diseases, short-term exposure

Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke

Objective: To explore the relationship between the total cerebral small vessel disease (CSVD) score and retinal vessel diameters in patients with mild stroke. Methods: The patients with mild stroke who were hospitalized in the Second People's Hospital of Changzhou, Nanjing Medical University from March to December 2019 were continuously collected (National Institutes of Health Stroke Scale score≤3 points). All patients completed the head magnetic resonance imaging and retinal fundus photography examination, and then the retinal arteriovenous diameter was measured semi-automatically based on the pictures. According to the total CSVD score (0-4 points), the patients were divided into 5 groups. The baseline characteristics of the patients were compared. Moreover, the correlation of total CSVD with retinal blood vessel diameters were analyzed by spearman and linear regression. Results: A total of 206 patients were enrolled. There were 69, 51, 41, 30, and 15 patients with 0, 1, 2, 3, and 4 points, respectively. In CSVD subgroups, there were significant differences in age, duration of hypertension and diabetes (all P<0.05). The central retinal artery equivalent (CRAE), (CSVD scores 0-4 were (126±12) μm, (118±11) μm, (108±11) μm, (99±8) μm, (90±7) μm, P<0.001) and arteriole-to-venule ratio (AVR) (CSVD scores 0-4 were 0.65±0.05, 0.60±0.04, 0.56±0.04, 0.49±0.03, 0.44±0.02, P<0.001) were different in CSVD subgroups. With the increase of CSVD score, the diameter of artery and AVR became smaller. The total CSVD was significantly correlated with AVR by Spearman correlation analysis (r= 0.818, P<0.001). By constructing a linear regression equation model, the coefficient of determination of the total CSVD score (R2=0.694) was higher than that of lacunes, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space. After adjusting for age, course of hypertension and diabetes, and different types of CSVD, further multiple linear regression analysis revealed that the total CSVD score was still an independent related factor of AVR (β=-0.039, P<0.001, 95%CI=-0.051--0.028). Conclusions: Total CSVD score is negatively correlated with retinal artery diameters and AVR. Additionally, the total CSVD score can better reflect the degree of cerebral microvascular lesions than single type CSVD.

Interocular asymmetry of the superonasal retinal nerve fibre layer thickness and blood vessel diameter in healthy subjects.

Optical coherence tomography is commonly used to measure the retinal nerve fibre layer thickness in both normal and diseased eyes; however, variation among normal eyes is common and may limit the usefulness of the results. The aim of this study was to explore the interocular asymmetries in retinal nerve fibre layer thickness in a group of normal eyes and to investigate the influence of blood vessel diameter on local retinal nerve fibre layer thickness. In this prospective study, retinal nerve fibre layer thickness and blood vessel diameter across 100 healthy participants were measured using two optical coherence tomography instruments. Individuals were categorised into two groups based on the presence or absence of interocular retinal nerve fibre layer thickness asymmetry beyond the 75th percentile of all participants. The superonasal sectoral retinal nerve fibre layer thickness was significantly greater in the left eye compared to the right, across all three sectors. Mean blood vessel diameter showed a corresponding difference in thickness at one of the superonasal sectors. Linear regression showed a positive and moderate correlation between blood vessel diameter and focal retinal nerve fibre layer thickness. This trend persisted across both arteries and veins, but veins showed larger variability between left and right eye in participants with marked superonasal retinal nerve fibre layer asymmetry. Retinal nerve fibre layer thickness and blood vessel diameter vary significantly between eyes even in healthy individuals. These asymmetries in a normal population should be taken into consideration when interpreting the retinal nerve fibre layer thickness measurements from optical coherence tomography to assist in distinguishing normal variations from disease.

Activation of transient receptor potential vanilloid 4 channels dilates rat retinal arterioles through nitric oxide- and BKCa channel-dependent mechanisms in vivo.

Transient receptor potential vanilloid 4 (TRPV4) channel, a cation channel expressed in nearly all cell types, plays an important role in the regulation of vascular tone. In the present study, we examined the effect of GSK1016790A, an activator of TRPV4 channels, on the diameter of retinal blood vessels in rats and the underlying mechanisms. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Intravenous infusion of GSK1016790A (0.2-2μgkg-1min-1) increased retinal arteriolar diameter in a dose-dependent manner. The higher dose of GSK1016790A (2μgkg-1min-1) slightly decreased blood pressure. These responses to GSK1016790A were significantly attenuated by intravenous injection of GSK2193874 (0.3mg/kg), an antagonist of TRPV4 channels. Intravitreal injection of Nω-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase or iberiotoxin, an inhibitor of large-conductance Ca2+-activated K+ (BKCa) channel, significantly attenuated the GSK1016790A-induced increases in retinal arteriolar diameter. These results suggest that activation of TRPV4 channels dilates rat retinal arterioles through NO- and BKCa channel-dependent mechanisms in vivo.

Hypercapnia Impairs Vasoreactivity to Changes in Blood Pressure and Intraocular Pressure in Rat Retina.

The balance between oxygen and carbon dioxide sets the resting tone (or diameter) of retinal blood vessels. Eyes that are hypercapnic use up their "vasodilatory reserve" and therefore fail to respond adequately to changes in intraocular or blood pressure. Retinal vessels are regulated by both myogenic and metabolic mechanisms. We considered whether alteration of metabolic status would modify the vascular response to ocular perfusion pressure (OPP) lowering in rat retina. In pentobarbital anesthetized adult Brown-Norway rats, normocapnia or hypercapnia was achieved by artificially ventilating animals with air or 5% carbon dioxide in ~30% oxygen, respectively. Ocular perfusion pressure was gradually reduced to ~20 mmHg by either lowering blood pressure (slowly drawing blood from a femoral artery/vein) or manometrically increasing intraocular pressure under normocapnic or hypercapnic conditions. In all four groups (n = 7 eyes for each), a confocal scanning laser ophthalmoscope was used to acquire image sequences centered on the optic nerve throughout pressure modification. The diameter of arterioles and venules at various OPP levels was measured and expressed as percentage relative to their own baseline. The response of arterioles and venules to OPP lowering was compared between normocapnic and hypercapnic groups. Average arterial carbon dioxide partial pressures were 36.9 ± 2.6 mmHg in normocapnic and 64.1 ± 5.9 mmHg in hypercapnic (P < .001) animals. In the normocapnic groups, blood pressure lowering and intraocular pressure elevation resulted in significant vasodilation of both arterioles and venules (P < .0001). In the hypercapnic groups, OPP lowering-induced vasodilation was significantly attenuated compared with the corresponding normocapnic groups (P < .0001 for both, two-way analysis of variance). Hypercapnia significantly modified myogenic vascular autoregulation in response to OPP reduction.

GGM classifier with multi-scale line detectors for retinal vessel segmentation

Persistent changes in the diameter of retinal blood vessels may indicate some chronic eye diseases. Computer-assisted change observation attempts may become challenging due to the emergence of interfering pathologies around blood vessels in retinal fundus images. The end result is lower sensitivity to thin vessels for certain computerized detection methods. Quite recently, multi-scale line detection method proved to be worthy for improved sensitivity toward lower-caliber vessels detection. This happens largely due to its adaptive property that responds more to the longevity patterns than width of a given vessel. However, the method suffers from the lack of a better aggregation process for individual line detectors. This paper investigates a scenario that introduces a supervised generalized Gaussian mixture classifier as a robust solution for the aggregate process. The classifier is built with class-conditional probability density functions as a logistic function of linear mixtures. To boost the classifier’s performance, the weighted scale images are modeled as Gaussian mixtures. The classifier is trained with weighted images modeled on a Gaussian mixture. The net effect is increased sensitivity for small vessels. The classifier’s performance has been tested with three commonly available data sets: DRIVE, SATRE, and CHASE_DB1. The results of the proposed method (with an accuracy of 96%, 96.1% and 95% on DRIVE, STARE, and CHASE_DB1, respectively) demonstrate its competitiveness against the state-of-the-art methods and its reliability for vessel segmentation.

Microvascular reactivity in rehabilitating cardiac patients based on measurements of retinal blood vessel diameters

BackgroundExercise-based rehabilitation improves general cardiovascular fitness. The impact on the microvascular system has been studied in less detail. We measured changes in retinal blood vessel diameters, as a proxy for microvascular reactivity, in cardiac patients and we assessed the impact of a rehabilitation program on retinal vessel diameters. DesignCardiac patients (n = 78) and age-matched healthy controls (n = 32) performed an initial maximal endurance cycling test. Patients then participated in a 12-week rehabilitation program with additional endurance tests being performed six and twelve weeks after the initial test. MethodsFundus images were collected immediately before and 0, 5, 10, 15 and 30 min after the endurance test. Widths of retinal blood vessels, represented as Central Retinal Arteriolar/Venular Equivalent (CRAE/CRVE) were calculated from the images. ResultsAt the start of the rehabilitation program, CRAE and CRVE values of the patients changed immediately after the endurance test with respectively −1.90 μm (95% CI: −3.58; −0.22) and −5.32 μm (95% CI: −7.33; −3.30) compared to baseline values. In contrast, CRAE and CRVE values of healthy controls were respectively increased [3.52 μm (95% CI: 2.34; 4.69)] and decreased [−3.17 μm (95% CI: −5.27; −1.07)]. After six and twelve weeks, CRAE responses of patients immediately after endurance test increased respectively with 5.98 μm (95% CI: 4.25; 7.71) and 4.44 μm (95% CI: 3.18; 5.71). These responses were similar to the microvascular reactions observed in the control group. ConclusionsArteriolar and venular retinal microvascular responses in cardiac patients were different from the ones of healthy controls. Retinal microvascular response of cardiac patients improved during rehabilitation.

Association of advanced oxidation protein product, thiobarbituric acid reactive substances and total sulfhydryl groups with retinal blood vessels caliber

Introduction/Objective. Intensive oxidative stress is proven in patients with diabetes mellitus and important in the development of a microvascular complication of type 2 diabetes mellitus. The aim of the study was to investigate the relationship between morphometric parameters of retinal blood vessels in patients with diabetic retinopathy (DR) and the levels of parameters of oxidative stress: advanced oxidation protein product (AOPP), thiobarbituric acid reactive substances (TBARS), and total sulfhydryl (SH) groups in blood samples. Methods. The patients (the group with DR and controls) were sex- and age-matched. Glycaemia, hemoglobin A1C HbA1C, total cholesterol and its fractions, and triglycerides were measured in blood samples. AOPP and total SH groups were determined in the plasma by specific methods. Modification of the thiobarbituric acid method was used for the determination of TBARS. The number and diameter of retinal blood vessels, as morphometric parameters on digital retinal photography, was determined by using the ImageJ software. Student?s t-test was used as the statistical method for the evaluation of differences between the morphometric and blood test parameters. The significance of differences in morphometric parameters of retinal blood was establish by one-way ANOVA. Results. Significantly higher levels of parameters of oxidative stress (AOPP and TBARS) were in the group of patients with DR than in the controls. This difference was also present among the patients with mild and severe forms of DR (AOPP F 77.03, p &lt; 0.001) (TBARS F 63.28, p &lt; 0.001). The diameter of retinal blood vessels correlated with levels of AOPP, but only in patients with mild DR. Conclusion. Parameters of oxidative stress, AOPP and TBARS, may be important for the follow-up of DR. In early stages in diabetic retinopathy, AOPP can be a valuable biomarker.

Ginsenoside Rb1 attenuates diabetic retinopathy in streptozotocin-induced diabetic rats1.

Purpose To investigated the effects of ginsenoside Rb1 on diabetic retinopathy in streptozotocin-induced diabetic rats. Methods Diabetes was induced by a single intraperitoneal injection of streptozotocin (80 mg/kg) in male Wistar rats. Ginsenoside Rb1 (20, 40 mg/kg) was injected (i.p.) once a day for 4 weeks. Then, using fundus photography, the diameter and vascular permeability of retinal vessels were investigated. Retinal histopathology was undertaken. Contents of malondialdehyde (MDA) and glutathione (GSH) in retinas were assayed. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione cysteine ligase catalytic subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM) were measured. Results Treatment with ginsenoside Rb1 attenuated the diabetes-induced increase in the diameter of retinal blood vessels. Ginsenoside Rb1 reduced extravasation of Evans Blue dye from retinal blood vessels. Ginsenoside Rb1 partially inhibited the increase in MDA content and decrease in GSH level in rat retinas. Nrf2 levels in the nuclei of retinal cells and expression of GCLC and GCLM were increased significantly in rats treated with ginsenoside Rb1. Conclusion These findings suggest that ginsenoside Rb1 can attenuate diabetic retinopathy by regulating the antioxidative function in rat retinas.

EFFECTS OF INTRAVITREAL RANIBIZUMAB AND BEVACIZUMAB ON THE RETINAL VESSEL SIZE IN DIABETIC MACULAR EDEMA.

The goal of this study was to assess the effects of a single injection of intravitreal ranibizumab (RAN) or bevacizumab (BEV) on the retinal vessel size in eyes with diabetic macular edema. In total, 32 patients were enrolled in the RAN group, and 30 patients were included in BEV group. Each of these groups was also subdivided into two others groups: a study group and a control group. The study groups were composed of the injected eyes, whereas the noninjected fellow eyes served as the control groups. The patients underwent complete ophthalmic examinations, including optical coherence tomography and fundus fluorescein angiography, and the primary outcome measures included the central retinal artery equivalent, central retinal vein equivalent, and artery-to-vein ratio. In the RAN study group (n = 32), the preinjection mean central retinal artery equivalent (175.42 μm) decreased to 169.01 μm after 1 week, and to 167.47 μm after 1 month (P < 0.001), whereas the baseline central retinal vein equivalent (235.29 μm) decreased initially to 219.90 μm after 1 week, and to 218.36 μm after 1 month (P < 0.001). In the BEV study group (n = 30), the preinjection central retinal artery equivalent (150.21 μm) decreased to 146.25 μm after 1 week, and to 145.89 μm after 1 month (P < 0.001); whereas the baseline central retinal vein equivalent (211.87 μm) decreased initially to 204.59 μm after 1 week and was 205.24 μm after 1 month (P < 0.001). The preinjection artery-to-vein ratio values changed significantly (P = 0.001) after 1 week and after 1 month in the RAN group, but no significant alteration in the artery-to-vein ratio was observed in the BEV group (P = 0.433). In both the RAN (n = 32) and BEV (n = 30) control groups, none of the 3 parameters changed throughout the study period, when compared with the baseline. The results of this study showed that both RAN and BEV injections significantly constricted the retinal blood vessel diameters.

A generalized multi-scale line-detection method to boost retinal vessel segmentation sensitivity

Many chronic eye diseases can be conveniently investigated by observing structural changes in retinal blood vessel diameters. However, detecting changes in an accurate manner in face of interfering pathologies is a challenging task. The task is generally performed through an automatic computerized process. The literature shows that powerful methods have already been proposed to identify vessels in retinal images. Though a significant progress has been achieved toward methods to separate blood vessels from the uneven background, the methods still lack the necessary sensitivity to segment fine vessels. Recently, a multi-scale line-detector method proved its worth in segmenting thin vessels. This paper presents modifications to boost the sensitivity of this multi-scale line detector. First, a varying window size with line-detector mask is suggested to detect small vessels. Second, external orientations are fed to steer the multi-scale line detectors into alignment with flow directions. Third, optimal weights are suggested for weighted linear combinations of individual line-detector responses. Fourth, instead of using one global threshold, a hysteresis threshold is proposed to find a connected vessel tree. The overall impact of these modifications is a large improvement in noise removal capability of the conventional multi-scale line-detector method while finding more of the thin vessels. The contrast-sensitive steps are validated using a publicly available database and show considerable promise for the suggested strategy.

Anti-diabetic drug metformin dilates retinal blood vessels through activation of AMP-activated protein kinase in rats

The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01–0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase. Similar results were obtained with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR, 0.01–1mg/kg/min). Neither metformin nor AICAR exerted significant effect on mean blood pressure and heart rate. However, a significant pressor response to AICAR was observed upon inhibition of NO synthase. These results suggest that metformin dilates retinal blood vessels through activation of AMPK, and NO plays an important role in the retinal vasodilator response following AMPK activation.