The role of arterial stiffness in the onset of Takotsubo cardiomyopathy observed with noradrenaline administration and intracranial blood injection in rabbits.

Takotsubo cardiomyopathy (TCM) has been reported to occur after subarachnoid hemorrhage, and the involvement of a critical activity of catecholamines has been mentioned, but the details of its onset have not been fully clarified. Recently, proper arterial stiffness could be measured with cardio-ankle vascular index. Therefore, we aimed to clarify the role of arterial stiffness in onset of TCM using rabbits under infusion of noradrenaline and injection of blood into brain ventricle. Rabbits were divided into three groups: infusion of noradrenaline (group A), infusion of noradrenaline + injection of saline into the brain ventricle (group B), infusion of noradrenaline + injection of blood in the brain ventricle (group C). Aortic arterial stiffness beta (Aß) and femoral arterial stiffness beta (Fß) were defined according to definition of the cardio-ankle vascular index. Blood pressure (BP), Aß, Fß, and femoral vessel resistance (FVR) were measured. Left ventricular movement were monitored with echocardiography. BP increased uniformly in all three groups. Fß in the group A, B and C increased from 3.6 ± 3.2, 3.6 ± 3.6 and 3.9_ ± 4.2 to 15 ± 2, 17.9 ± 2.4, 34.8 ± 9.1 due to the ICP enhancements in addition to noradrenaline administration, respectively. Fß in groups B and C was significantly larger than that in group A. On echocardiography, a much higher akinesic area of the apex was observed in group C compared with group A and B. Cardiac movements similar to TCM were observed slightly in group B and definitely in group C. Noradrenaline administration infusion and blood injection into the brain ventricle induced TCM accompanying with enhanced femoral arterial stiffness. These results suggested that elevated arterial stiffness might be involved in the formation of TCM in addition to a critical activity of catecholamines and an increase in intracranial pressure with blood injection.

Analysis of effects of acute hypovolemia on arterial stiffness in rabbits monitored with cardio-ankle vascular index.

Although elasticity of the conduit arteries is known to be contribute effective peripheral circulation via Windkessel effects, the relationship between changes in intra-aortic blood volume and conduit artery elasticity remains unknown. Here we assessed the effects of change in intra-aortic blood volume induced by blood removal and subsequent blood transfusion on arterial stiffness and the involvement of autonomic nervous activity using our established rabbit model in the presence or absence of the ganglion blocker hexamethonium (100 mg/kg). Blood removal at a rate of 1 mL/min gradually decreased the blood pressure and blood flow of the common carotid artery but increased a stiffness indicator the cardio-ankle vascular index, which was equally observed in the presence of hexamethonium. These results suggest that arterial stiffness acutely responds to changes in intra-aortic blood volume independent of autonomic nervous system modification.

Effect of nicorandil administration on cardiac burden and cardio-ankle vascular index after coronary intervention.

Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).

Physiological role of nitric oxide for regulation of arterial stiffness in anesthetized rabbits.

We assessed effects of acetylcholine and Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) on the cardio-ankle vascular index (CAVI), an indicator of arterial stiffness from origin of aorta to tibial artery, in halothane-anesthetized rabbits. Acetylcholine decreased the blood pressure, femoral vascular resistance and CAVI, whereas l-NAME did not affect the CAVI at a hypertensive dose. The acetylcholine-induced decrement of CAVI was completely suppressed by l-NAME. These results suggest that the arterial stiffness in rabbits may be independent from homeostatic production of nitric oxide, however, it can be decreased by large amounts of nitric oxide that are intrinsically produced by exogenously administered acetylcholine.

Pulse Waveform Analysis in Ocular Microcirculation by Laser Speckle Flowgraphy in Patients with Left Ventricular Systolic and Diastolic Dysfunction.

PURPOSE: To determine: (1) whether variables of a pulse wave form analysis of ocular microcirculation shown by laser speckle flowgraphy (LSFG) correlate with left ventricular (LV) systolic dysfunction and (2) whether these variables correlate with LV diastolic dysfunction in subjects without LV systolic dysfunction as assessed by echocardiography. METHODS: We studied 200 consecutive subjects. LV systolic dysfunction has been determined to be present when the LV ejection fraction was < 50%. LV diastolic dysfunction was diagnosed when subjects had an E/e' ratio ≥15 and an e' velocity < 10 cm/s. We evaluated the pulse waveform analysis variables "rising rate" and the blowout score (BOS) using LSFG in the optic nerve head (ONH) and choroid. RESULTS: The brain natriuretic peptide (BNP) level, the rising rate in the choroid area (rising rate-choroid), and heart rate were revealed as independent factors for LV systolic dysfunction, and BOS-choroid was identified as an independent factor for LV diastolic dysfunction. The areas under the curve (AUC) of BNP and rising rate-choroid for LV systolic dysfunction were 0.83 and 0.81, respectively. The AUC of BOS-choroid for LV diastolic dysfunction was 0.73. CONCLUSION: Pulse waveform analysis in the choroid has a significant correlation with LV systolic and LV diastolic function.

Assessment of ocular microcirculation in patients with end-stage kidney disease.

PURPOSE: To determine the impact that end-stage kidney disease (ESKD) has on ocular microcirculation in the optic nerve head (ONH) and choroid area shown by laser speckle flowgraphy (LSFG). METHODS: We studied 24 consecutive Japanese patients with ESKD who visited the department of Nephrology at our hospital and 55 age- and gender-matched subjects who had undergone polysomnography. The mean blur rates (MBRs) in vessels (MBR-Vessel), in the tissue (MBR-Tissue), throughout the ONH (MBR-All), and throughout the choroid (MBR-Choroid) were analyzed. We divided the MBR-Tissue into four sections (superior, temporal, inferior, and nasal). The results of systemic and ocular parameters were compared between the ESKD patients and control subjects. We performed single and multiple regression analyses to determine the MBR section(s) that correlated most strongly with serum creatinine and the estimated glomerular filtration rate (eGFR) and to identify the independent factors for selected MBR sections in the ESKD patients. RESULTS: All sections of the ONH in the ESKD patients were significantly lower than those in the control subjects. MBR-Choroid was not significantly different between the control and ESKD groups. The single regression analyses revealed that MBR-Tissue had the strongest correlations with creatinine and the eGFR. The multiple regression analyses revealed hematocrit, creatinine, and eGFR as factors independently contributing to the MBR-Tissue. The inferior section of MBR-Tissue was most strongly correlated with creatinine and the eGFR. CONCLUSION: The MBRs in the ONH of the ESKD patients decrease compared with control subjects and the inferior section of MBR-Tissue is correlated with serum creatinine and eGFR.

Differences in optic nerve head microcirculation between evening and morning in patients with coronary artery disease.

PURPOSE: To determine whether differences or variation of blood flow in the ONH are independent risk factors for CAD. METHODS: We studied 144 consecutive patients whose ocular blood flow in the ONH was measured in the evening and morning by LSFG. We analyzed the MBR throughout the ONH (MBR-A) and in the tissue (MBR-T) and vessels (MBR-V) in the ONH. We also evaluated the MBR-T, MBR-V, and MBR-A values obtained in the evening and morning and the variation (Δ) between evening and morning values in each group. RESULTS: Twenty-three patients (16%) were diagnosed with CAD. The morning MBR-T and MBR-A values were significantly lower in these patients with CAD compared to the patients without CAD. ΔMBR-T in the CAD patients was significantly lower compared to that of the no-CAD patients. The logistic regression analysis was revealed that a high carotid artery plaque score, lower ΔDBP, and ΔMBR-T were identified as risk factors for CAD. CONCLUSIONS: Ocular microcirculation obtained from LSFG may provide a window for detecting changes in microvasculature related to CAD.

Arterial stiffness shown by the cardio-ankle vascular index is an important contributor to optic nerve head microcirculation.

PROPOSE: The purpose of this study was to determine whether there were significant correlations between the pulse waveform in the capillary area of the optic nerve head (ONH) microcirculation shown by laser speckle flowgraphy (LSFG) and parameters of the systemic condition, especially the cardio-ankle vascular index (CAVI). METHOD: We studied 130 men (ages 60.5 ± 10.9 years) who visited the Vascular Function Section of the Department of Cardiovascular Center of Toho University Sakura Medical Center. We evaluated the skew and blowout time (BOT) - which are parameters of pulse waveform analyses - using LSFG in the capillary area of the ONH for each patient. The CAVI, the E/e' ratio as the measure of diastolic left ventricular function, and the mean intima-media thickness (IMT) were evaluated as systemic parameters. We performed a Pearson's correlation analysis and a multiple regression analysis to determine independent factors for skew and BOT. RESULTS: Heart rate, spherical refraction, and the CAVI (standard regression = 0.18, t = 2.61, p = 0.01) were revealed as factors contributing independently to the skew by multiple regression analysis. Heart rate, the CAVI (standard regression = -0.27, t = -3.92, p = 0.0002), the urinary albumin concentration, the mean IMT, spherical refraction, body mass index and pulse pressure were revealed as factors contributing independently to the BOT by multiple regression analysis. CONCLUSION: The CAVI was demonstrated to be an independent factor contributing to both skew and BOT in the capillary area of the ONH. Our findings clarified that large arterial function shown by the CAVI contributes to smooth hemodynamics of microcirculation, shown by LSFG.

Soluble form of LR11 is highly increased in the vitreous fluids of patients with idiopathic epiretinal membrane.

PURPOSE: LR11 (also called SorLA or SORL1) is a migration regulator of adherent cells with the immature proliferative phenotype. The present study investigated the clinical and pathological involvement of the soluble form of LR11 (sLR11) in the idiopathic epiretinal membrane (iERM). METHODS: The subjects were 51 patients with iERM (24 cellophane macular reflex (CMR) and 27 preretinal macular fibrosis (PMF)) and 45 patients with macular holes as age and sex-matched controls. Vitreous sLR11 and transforming growth factor (TGF)ß2 levels were measured by ELISA. RESULTS: The sLR11 levels in the vitreous fluids of patients with iERM (20.2 ± 8.1 ng/mL) were significantly higher than those in controls (11.4 ± 4.7 ng/mL). Among the patients with iERM, the vitreous sLR11 levels were significantly higher in PMF (23.6 ± 8.2 ng/mL), than those in CMR (16.5 ± 5.9 ng/mL). Multivariate regression analysis of the studied factors showed that sLR11 was a unique factor independently contributing to the discrimination of the iERM patients against the control subjects (odds ratio [OR] 1.35 per 1-ng/mL increase, 95% CI 1.09-1.67; P = 0.004). ROC analysis showed that the sensitivity and the specificity of sLR11, but not of other studied factors, categorized into the rank of moderate accuracy. Finally, there was a positive correlation (R = 0.588; P = 0.003) between the vitreous levels of sLR11 and TGFß2 using the available samples. CONCLUSIONS: sLR11 levels in vitreous fluids were specifically increased in patients with iERM, suggesting the involvement in the pathology of proliferative and migrating cells for the development of iERM.

Relationship between glycosylated hemoglobin A1c and ocular circulation by laser speckle flowgraphy in patients with/without diabetes mellitus.

PURPOSE: To determine whether there are significant correlations between the hemodynamics of the optic nerve head (ONH) and choroid as shown by laser speckle flowgraphy (LSFG) and the fasting blood sugar (FBS) and HbA1c level in patients with/without diabetes mellitus (DM). METHODS: We analyzed 196 consecutive patients (151 men, 45 women). The pulse waveform analysis parameters of the mean blur rate (MBR), blowout score (BOS) and blowout time (BOT) in the ONH and choroid were evaluated. We used a multiple regression analysis to determine the independent factors for the LSFG parameters that are significantly correlated with FBS or HbA1c. We evaluated the relationship between the LSFG parameters FBS and HbA1c obtained from the 147 non-DM patients. RESULTS: The multiple regression analysis revealed that hematocrit and HbA1c were factors contributing independently to the choroid MBR. The age, gender, pulse pressure, heart rate, spherical refraction and HbA1c were identified as factors contributing independently to the BOS in the ONH. The multiple regression analysis indicated that age, height, pulse pressure, heart rate and HbA1c were factors contributing independently to the BOS in the choroid. A Pearson's correlation analysis showed that the BOT values in the ONH and choroid were significantly correlated with the HbA1c in the non-DM patients. CONCLUSION: Our results confirmed that HbA1c, even within the normal range, affected the blood flow in the ONH and choroid. LSFG may be a useful method to detect abnormalities of asymptomatic ocular circulation.

Pulse waveform analysis in the optic nerve head circulation reflects systemic vascular resistance obtained via a Swan-Ganz catheter.

PURPOSE: To determine whether a pulse waveform analysis in the optic nerve head (ONH) circulation as determined by laser speckle flowgraphy (LSFG) can provide systemic hemodynamic values - the systemic vascular resistance (SVR) in particular - similar to those obtained by using a Swan-Ganz catheter, which is an invasive method. METHOD: Sixteen consecutive subjects were examined. Hemodynamic monitoring was obtained from right heart catheterization with a Swan-Ganz catheter and coronary angiography without an intracoronary nitroglycerin administration. Direct blood pressure was measured with a trans-radial approach. Single regression analyses were used to determine the relationship between the blowout score and blowout time, which are the items of the pulse waveform analysis in the ONH, by using LSFG and the hemodynamic parameters. RESULTS: The blowout time was significantly and negatively correlated with the SVR (r = -0.52, p = 0.04), the ocular perfusion pressure with the mean arterial blood pressure of the radial artery (r = -0.52, p = 0.04) and the radial artery pulse pressure (r = -0.52, p = 0.04).The pulmonary capillary wedge pressure (r  = -0.44, p = 0.09) and the mean arterial blood pressure of the radial artery (r  = -0.44, p = 0.09) tended to be correlated with the blowout time, but did not reach significance. The blowout score was significantly and negatively correlated with the radial artery blood pressure (r = -0.51, p = 0.046). CONCLUSION: A pulse waveform analysis in the ONH by LSFG may be one of the useful methods for understanding the SVR.

Relationship between plasma levels of vasoactive mediators and optic nerve head circulation shown by laser speckle flowgraphy.

PROPOSE: To evaluate relationships between optic nerve head (ONH) circulation by laser speckle flowgraphy (LSFG), and secretion levels of plasma norepinephrine (NE), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma cortisol. METHOD: Forty subjects were included in the study. The mean blur rates (MBR) throughout the ONH (MBR-all), in the tissue (MBR-tissue), and in vessels (MBR-vessel) were analyzed. In 29 subjects the following parameters were evaluated: plasma NE and ONH circulation in the evening and morning (Δ plasma NE, Δ MBR-all, -tissue, -vessel, and Δ area ratio of blood stream). RESULTS: Plasma NE was significantly correlated with MBR-all (r = 0.39, P = 0.01) and MBR-vessel (r = 0.51, P = 0.0008). Plasma cortisol was significantly correlated with MBR-vessel (r =0.35, P = 0.03). The PRA (r = 0.31, P = 0.05) and PAC (r = 0.31, P = 0.05) tended to correlate with MBR-vessel. The multiple regression analysis revealed that plasma NE, PAC, and ocular perfusion pressure (OPP) were identified as factors contributing independently to the MBR-vessel (plasma NE: standard regression = 0.48, t-value = 3.12, P = 0.004; PAC: 0.43, 3.10, 0.04; OPP: 0.58, 2.34, 0.03, r = 0.71). Positive correlations between Δ plasma NE and Δ MBR-all (r = 0.46, P = 0.01), Δ MBR-tissue (0.38, 0.04), Δ MBR-vessel (0.41, 0.03), and Δ area ratio of blood stream (0.38, 0.04) were observed. CONCLUSION: Our results clarified that the measurements of ONH circulation by LSFG is reflecting the plasma secretion levels of vasoactive mediators.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). METHODS: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. RESULTS: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with x0394;serum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for x0394;CAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for x0394;mean IMT. CONCLUSION: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

Cardio-ankle vascular index (CAVI) differentiates pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbits.

Cardio-ankle vascular index (CAVI) has been developed for measurement of vascular stiffness from the aorta to tibial artery, which is clinically utilized for assessing the progress of arteriosclerosis. In this study, we established measuring system of the CAVI in rabbits, and assessed whether the index could reflect different pharmacological actions of nitroglycerin and nicardipine on the systemic vasculature. Rabbits were anesthetized with halothane, and the CAVI was calculated from the well-established basic equations with variables obtained from brachial and tibial blood pressure and phonocardiogram. Nicardipine (1, 3 and 10 µg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and heart-ankle pulse wave velocity (haPWV). Meanwhile, no significant change was detected in the CAVI at the low or middle dose, which reflects the defining feature of the CAVI that is independent of blood pressure. The index increased at the high dose. Nitroglycerin (2, 4 and 8 µg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and haPWV. Meanwhile, the CAVI was decreased during the nitroglycerin infusion, which may reflect its well-known pharmacological action dilating conduit arteries. These results suggest that the CAVI differentiates the properties of these vasodilators in vivo.

Pulse waveform analysis of optic nerve head circulation for predicting carotid atherosclerotic changes.

PURPOSE: To evaluate the relationship between the parameters of pulse waveform analysis in the optic nerve head using laser speckle flowgraphy (LSFG) and intima-media thickness (IMT) and severity of carotid arterial plaque. DESIGN: Prospective and cross-sectional study. METHODS: One hundred seventy-six subjects were studied. Mean IMT and plaque score obtained from high-resolution B-mode ultrasound were evaluated. If mean IMT was 1 mm or greater, abnormal carotid artery thickening was diagnosed; if the plaque score exceeded 10, severe atherosclerosis was diagnosed. Blowout time and blowout score, which are parameters of pulse waveform analysis using LSFG, were evaluated. Logistic regression analyses determined the independent factors for abnormal carotid artery thickening and severe atherosclerosis. The cutoff levels for abnormal carotid artery thickening and severe atherosclerosis were analyzed using a conventional receiver operating characteristic (ROC) curve. RESULTS: Logistic regression analysis showed that blowout time and body mass index contributed independently to abnormal carotid artery thickening, and blowout score contributed independently to severe atherosclerosis. The ROC curve showed that sensitivity and specificity of the blowout time and blowout score were equivalent to or greater than those of other factors. The cutoff level of the blowout time for abnormal carotid artery thickening was 46.4; the cutoff level of the blowout score for severe atherosclerosis was 71.8. CONCLUSIONS: Measurement of blowout time and blowout score in the optic nerve head by LSFG can be useful for evaluating mean IMT and plaque score, which are parameters of carotid atherosclerosis.

Relationships among serum lipoprotein lipase mass, visceral fat, and retinal nerve fiber layer thickness.

PURPOSE: The purpose of the study was to determine whether there were significant correlations among the serum lipoprotein lipase mass, visceral fat, and the retinal nerve fiber layer (RNFL) thickness. METHODS: We studied 118 consecutive subjects. Optical coherence tomography (OCT) was used to measure the RNFL thickness. The Pearson correlation coefficient was used to determine the relationships among lipoprotein lipase (LPL) mass, visceral fat area by computed tomography, OCT, and other parameters. We performed a multiple regression analysis to identify independent factors for the RNFL sectors that were the most strongly correlated with the LPL mass and visceral fat area. RESULTS: The LPL mass was significantly correlated with the nasal RNFL thickness in both eyes (right eye: r = 0.24, p = 0.008, left eye: 0.32, 0.0008) and inferior RNFL thickness in the left eye ( r = 0.23, p = 0.01). The visceral fat area was significantly correlated with the nasal RNFL thickness in both eyes (right eye: r = -0.19, p = 0.04, left eye: -0.30, 0.0008) and the inferior RNFL thickness in the left eye ( r = -0.23, p = 0.01). The subcutaneous fat area was not significantly correlated with any OCT parameters. The multiple regression analysis revealed that age, LPL mass, and visceral fat area were independent contributors to the nasal RNFL thickness in the left eye (age, standard regression coefficient = -0.34 , p = 0.0004; LPL mass, 0.26, 2.49, 0.01; visceral fat area, -0.21, 0.03). CONCLUSION: A reduction of lipoprotein lipase and accumulation of visceral fat might produce retinal neurodegenerative disorders that decrease the RNFL thickness, especially on the nasal side.

Evaluation of Carotid Atherosclerosis, Peripheral Arterial Disease, and Chronic Kidney Disease in Patients with Exudative Age-Related Macular Degeneration without Coronary Artery Disease or Stroke.

PURPOSE: To evaluate the risk factors for acute atherothrombotic events in patients with exudative age-related macular degeneration (AMD) without a history of coronary artery disease or stroke. METHODS: Two hundred fifty-nine patents with exudative AMD were evaluated for carotid atherosclerosis, peripheral arterial disease, and chronic kidney disease (CKD). RESULTS: A mean intima-media thickness of ≥1.0 mm was found in 28.2% of patients; 8.9% of patients had severe carotid artery stenosis. The prevalence rates of severe atherosclerosis with a plaque score >10, peripheral arterial disease, and CKD were 16.6, 5.4, and 32%, respectively. Diabetes mellitus and AMD affecting eyes bilaterally were identified as risk factors for abnormal carotid artery thickening, and age and body mass index were identified as risk factors for CKD. CONCLUSION: The current study confirmed that potentially 30% of patients with exudative AMD without a history of coronary artery disease or stroke have a high risk of acute atherothrombotic events.

H2O2-induced decomposition of layer-by-layer films consisting of phenylboronic acid-bearing poly(allylamine) and poly(vinyl alcohol).

Layer-by-layer (LbL) films were prepared by an alternate deposition of phenylboronic acid-bearing poly(allylamine hydrochloride) (PBA-PAH) and poly(vinyl alcohol) (PVA) on the surface of a quartz slide to develop thin films that can be decomposed in response to hydrogen peroxide (H2O2). The PBA-PAH/PVA films decomposed in the presence of H2O2; the degree and kinetics of decomposition depend on the concentration of H2O2 and on the pH of the solution. For example, the film decomposition completely occurred in 30 min in 1.0 mM H2O2 solution at pH 7.4, while it took 180 min in 0.1 mM H2O2 solution. The H2O2-induced decomposition of the film can be explained in terms of the oxidative scission of the carbon-boron bond in PBA residues in the PBA-PAH chains. A potential use of the PBA-PAH/PVA films in developing H2O2-sensitive delivery systems was suggested.

Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration.

BACKGROUND: To evaluate the plasma vascular endothelial growth factor (VEGF) levels after one intravitreal injection of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD). METHODS: Twenty-four Japanese with exudative AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation were included. Fourteen patients received an intravitreal injection of aflibercept, and ten patients received an intravitreal injection of ranibizumab. Plasma VEGF levels were evaluated within 7 days before the intravitreal injections and 1 day, 1 week, and 1 month after the intravitreal injection. RESULTS: In the ranibizumab group, the mean plasma VEGF levels were 245.7 ± 233.4 pg/ml before the injection, 246.6 ± 304.8 pg/ml after 1 day, 217.8 ± 212.9 pg/ml after 1 week, and 260.0 ± 290.1 pg/ml after 1 month. The plasma VEGF levels did not decrease significantly in patients in the ranibizumab group at any time point. In the aflibercept group, the mean plasma VEGF levels were 280.0 ± 170.3 pg/ml before the intravitreal injection and 8.2 ± 12.9 pg/ml after 1 day, 9.1 ± 9.1 pg/ml after 1 week, and 41.9 ± 41.4 pg/ml after 1 month (p < 0.0001, vs before injection). CONCLUSION: Intravitreally injected aflibercept reduced plasma VEGF over at least 1 month. In contrast, intravitreal injection of ranibizumab did not cause a significant reduction in the plasma VEGF levels.