Characteristics of laterality in the optic nerve head microcirculation obtained by laser speckle flowgraphy in healthy subjects.

PURPOSE: To determine the characteristics of the laterality of the ocular microcirculation parameters obtained from laser speckle flowgraphy (LSFG) in the optic nerve head (ONH). SUBJECTS AND METHODS: We reanalyzed a total of 240 healthy subjects (169 men, 71 women) who had participated in a medical checkup program. We analyzed the average mean blur rate (MBR), maximum MBR (Max-MBR), minimum MBR (Min-MBR), and area ratio of the blood stream (ARBS). As the pulse waveform parameters, we also calculated the skew, blowout score (BOS), blowout time (BOT), rising rate, falling rate, flow acceleration index (FAI), acceleration time index (ATI), resistivity index (RI), and beat strength over MBR (BOM). All parameters were compared between left and right eyes. RESULTS: MBR-average, MBR-Max, MBR-Min, ARBS, skew, BOT, rising rate, falling rate, FAI, ATI, and ARBS did not differ significantly between the right and left eyes. The BOS in the right eyes was significantly lower than that of the left eyes, and the RI and BS in the right eyes were significantly higher than those of the left eyes. Similarly, for the whole of the ONH, the BOS in the tissue area (Tissue) and in the vessel area (Vessel) of the right eyes were significantly lower than those of the left eyes, and RI-Tissue, RI-Vessel, BOM-Tissue, and BOM-Vessel in the right eyes were significantly higher than those of the left eyes. CONCLUSION: By using LSFG, we observed laterality of the BOS, RI, and BOM, all of which are pulse wave form parameters in the ONH.

The influence of hemorrhagic shock on ocular microcirculation by obtained by laser speckle flowgraphy in a white rabbit model.

PURPOSE: To clarify the continuous changes in the retinal vessels' and choroid's microcirculation during hemorrhagic shock and resuscitation in a rabbit model. METHODS: Hemorrhagic shock by the removal of blood (30 mL) and resuscitation by a blood-return technique was induced in anesthetized male New Zealand White rabbits (n = 10). We evaluated the retinal vessel blood flow (relative flow volume: RFV) and choroidal blood flow (mean blur rate in the choroid area: MBR-CH) by laser speckle flowgraphy (LSFG), with simultaneous measurements of systemic hemodynamics and laboratory parameters. RESULTS: RFV and MBR-CH showed significant decreases immediately after the initiation of blood removal and recovered by blood return. The lactate concentration tended to increase from baseline by the blood-removal operation, and it was significantly higher at the end of observation period. The %RFV and %MBR-CH each showed a significant positive correlation with mean arterial blood pressure, cardiac output, carotid blood flow, and central venous pressure. %RFV showed a significant positive correlation with %central venous oxygen saturation and negatively correlated with %lactate. The %hemoglobin did not show a significant correlation with %RFV or %MBR-CH. CONCLUSION: This rabbit hemorrhagic shock model confirmed that ocular microcirculation measurements by LSFG feasibly reflect variations in systemic hemodynamics during hemorrhagic shock and recovery.

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.

Intravitreal bevacizumab treatment reduces ocular blood flow in retinopathy of prematurity: a four-case report.

PURPOSE: To evaluate the relationship between ocular blood flow, expressed as mean blur rate (MBR) by laser speckle flowgraphy, and intravitreal bevacizumab (IVB) therapy in neonates with retinopathy of prematurity (ROP). METHODS: This was a case series study of 4 neonates with ROP under sedation before and after IVB and evaluated 8 eyes, in which the circulation could be measured three times consecutively. We performed optic nerve head blood flow measurement and fluorescein angiography (FA) before and 1 week after treatment. Blood flow was analyzed separately for MBR-A (mean of all values), MBR-V (vessel mean), and MBR-T (tissue mean). Comparisons between the MBR (-A, -V, -T), body weight, and other systemic and ocular parameters before and after treatment were performed using a paired t test. RESULTS: The MBR values after IVB were lower than the pre-treatment values in all cases. All eyes showed leakage at neovascularization on FA before treatment. Although leakage improved 1 week after treatment, the neovascularization did not completely regress. CONCLUSIONS: IVB improves vein dilation and artery tortuosity, while reducing ocular blood flow in neonates with ROP. We suggest that neovascularization might not be involved in reducing ocular blood flow in the early stage of IVB treatment.

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.

Retinal VEGF levels correlate with ocular circulation measured by a laser speckle-micro system in an oxygen-induced retinopathy rat model.

PURPOSE: We used a Laser speckle flowgraphy (LSFG)-micro system to examine the relationship between ocular blood flow and retinal vascular endothelial growth factor (VEGF) at retinopathy onset in oxygen-induced ischemic retinopathy (OIR) model rats. METHODS: Sixteen 50/10 OIR rats were compared with 17 control rats reared in room air. In postnatal day 14 (P14) and P18 rats, we measured and analyzed the left eye's mean blur rate (MBR) by setting a rubber band on the optic nerve head center, using the LSFG-Micro. At P18, the rats were sacrificed and their left-eye retinas were fixed, flat-mounted and stained with adenosine diphosphatase (ADPase). The right-eye retinas were homogenized; the lysate was centrifuged for an enzyme-linked immunosorbent assay (ELISA). The avascular area was measured as the percentage (%AVA) of the total retinal area. Retinal VEGF was measured by an ELISA. RESULTS: The examination's reproducibility was good. Our multivariate linear mixed model analysis revealed significantly high MBRs in the OIR rats (p = 0.0017). In the P18 OIR rats, significant correlations were seen between the MBR and %AVA (r = 0.80, p = 0.0002) and between the MBR and VEGF (r = 0.76, p = 0.0006). CONCLUSIONS: The LSFG-Micro provided reproducible blood flow measurements in neonatal rats. Because of the vitreous blood vessels, measurement of only the retinal vessels was not possible. However, the MBR was higher in the OIR rats than in the control rats, and the MBR and %AVA were correlated, as were the MBR and retinal VEGF. The MBR may thus serve as an indicator of OIR severity.

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.

Ocular blood flow values measured by laser speckle flowgraphy correlate with the postmenstrual age of normal neonates.

PURPOSE: To evaluate the relationships between optic nerve head (ONH) blood flow by laser speckle flowgraphy (LSFG), and postmenstrual age and body weight in normal neonates. METHODS: During their normal sleep, we studied 24 infants (postmenstrual age, 248-295 days) whose ocular blood flow could be measured three consecutive times. While the subjects slept in the supine position, three mean blur rate (MBR) values of the ONH were obtained: the MBR-A (mean of all values), MBR-V (vessel mean) and MBR-T (tissue mean) in the ONH. With regard to eye diseases, no retinopathy of prematurity (ROP) was observed, and no severe systemic diseases requiring treatment were noted in the subjects. Pearson's correlation coefficients were used to determine the relationship between the MBR-A, -V, -T and postmenstrual age (days) and body weight (g). RESULTS: Postmenstrual age was significantly correlated with MBR-A (r = 0.64, p = 0.0007), MBR-V (r = 0.62, p = 0.0012) and MBR-T (r = 0.62, p = 0.0012). However, the body weight was not correlated with the MBR (MBR-A: r = 0.37, p = 0.07, MBR-V: r = 0.31, p = 0.14, MBR-T: r = 0.38, p = 0.06). CONCLUSIONS: Our results clarified that the values of ocular blood flow measured by LSFG correlate with the postmenstrual age of normal neonates.

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.

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.

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.

[Comparison of antioxidant capacities in serum and vitreous fluids of vitreoretinal diseases].

PURPOSE: To investigate serum antioxidant potential of patients with vitreoretinal diseases that require vitreous surgery and the antioxidant potential in vitreous fluids obtained intraoperatively. SUBJECTS AND METHODS: Twenty seven eyes of 27 patients who had undergone vitrectomy for macular edema associated with branch retinal vein occlusion (BRVO), proliferative diabetic retinopathy (PDR), macular hole (MH)/epiretinal membrane (ERM) at Toho University Sakura Medical Center were studied. The biological anti-oxidant potential (BAP), as an index of anti-oxidant potential of serum and vitreous fluid was measured using a free radical elective evaluator (FREE). RESULTS: The vitreous BAP levels (microEq/l) in the PDR group was 1843 +/- 402 and in the BRVO group, 2120 +/- 413. The BAP levels in the vitreous fluid of the PDR and BRVO were significantly lower than those of control subjects. The serum BAP levels (microEq/l) in the PDR group was 2307 +/- 51.9 and in the BRVO group, 2390 +/- 149. The serum BAP levels in the PDR group were significantly lower than those in the control group. Only in the PDR group, the serum BAP was significantly lower than the vitreous BAP. The vitreous BAP levels were significantly positively correlated with those of the serum. CONCLUSIONS: A difference was shown between the antioxidant potentials of the vitreous fluid and serum in the patients with PDR. Antioxidant potential in the eye had possibly declined in patients with ischemic vitreoretinal disease compared with other vitreoretinal diseases.