Arteriovenous Oxygen Saturation Difference Research Articles

Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics. A total of 40 subjects were included in the present study, of which 29 had recovered from moderate to severe COVID-19 within 2 to 23 weeks before inclusion and 11 had never had COVID-19, as confirmed by antibody testing. Perfusion in retinal vessels was significantly lower in patients (60.6 ± 16.0 a.u.) than in control subjects (76.2 ± 12.1 a.u., p = 0.006). Arterio-venous (AV) difference in oxygen saturation and AVR was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). Molecular profiles demonstrated down-regulation of cell adhesion molecules, NOTCH3 and fatty acids, and suggested a bisphasic dysregulation of nitric oxide synthesis after COVID-19 infection. The results of this study imply that retinal perfusion and oxygen metabolism is still significantly altered in patients well beyond the acute phase of COVID-19. This is also reflected in the molecular profiling analysis of blood plasma, indicating a down-regulation of nitric oxide-related endothelial and immunological cell functions.Trial Registration: ClinicalTrials.gov (https://clinicaltrials.gov) NCT05650905.

Pretreatment ocular blood flow and retinal oxygen metabolism inthe acute uveitic phase is associated with final outcome in Vogt-Koyanagi-Harada disease.

To investigate the association between pretreatment blood flow velocity in the choroid and optic nerve head (ONH) and retinal oxygen metabolism in the acute uveitic phase and the development of 'sunset glow fundus' in Vogt-Koyanagi-Harada (VKH) disease. Retrospective analysis of 41 patients (82 eyes). Laser speckle flowgraphy and retinal oximetry measurements were performed at the presentation. The main outcome measure was the development of 'sunset glow fundus'. Twenty patients (40 eyes) presented in the phase preceding anterior segment inflammation (early presentation), and 21 patients (42 eyes) presented with anterior segment inflammation (late presentation). In ONH, mean blur rate (MBR)-vessel, representing blood flow velocity in retinal vessels, was significantly lower in the late presentation group, while choroidal MBR was not significantly different. The late presentation group had significantly lower oxygen saturation in retinal venules, a higher arteriovenous oxygen saturation difference and a smaller calibre of retinal arterioles compared with the early presentation group. Eyes that subsequently developed 'sunset glow fundus' had significantly lower ONH MBR-vessels, lower oxygen saturation in retinal venules, a higher arteriovenous oxygen saturation difference and a smaller calibre of retinal arterioles compared with eyes without 'sunset glow fundus'. ONH MBR-vessel had a significant negative correlation with arteriovenous oxygen saturation difference and a significant positive correlation with calibre of retinal arterioles. In the acute uveitic phase of VKH disease, the development of 'sunset glow fundus' is associated with pretreatment reduced retinal blood flow velocity, calibre of retinal arterioles and oxygen saturation in retinal venules, as well as an increased arteriovenous oxygen saturation difference.

Abstract 12910: Exercise Hemodynamics Unmasks Stage C Heart Failure With Preserved Ejection Fraction and Impaired Peripheral Oxygen Extraction in Stage A/B Patients in a Safety-Net Center

Introduction: There is a gap in research evaluating hemodynamics and impaired peripheral oxygen extraction in Stage A/B HFpEF in diverse groups. We sought to characterize the prevalence of impaired cardiac/peripheral profiles in Stage A/B HFpEF at Boston Medical Center. Hypothesis: We hypothesize both abnormal cardiac and peripheral profiles will be unmasked in exercising Stage A/B HFpEF patients. Methods: Invasive cardiopulmonary exercise testing (iCPET) was performed in 30 individuals with Stage A/B HFpEF. Significant valvular or pulmonary disease were excluded. Criteria for an impaired cardiac profile, with reclassification to Stage C, included exercise PCWP ≥ 25 mmHg or ΔPCWP/ΔCO slope > 2 mmHg/L/min. An impaired peripheral profile was defined as O 2 extraction ratio (peak arterio-venous oxygen saturation difference)/ (1.34*rest hemoglobin*rest arterial O 2 saturation) < 50%. With an approved IRB, the analysis was conducted in R. Results: Cohort clinical data shown in Table with 47% non-white and 57% female patients. Exercise unmasked Stage C HFpEF in 23 (77%) of cases; 17% had an impaired peripheral profile (O 2 extraction ratio 43 ± 7) and 10% (3 out of 30 patients) had concomitant impaired cardiac and peripheral profiles. Both cardiac and peripheral metrics correlated to metabolic parameters: peak oxygen consumption correlated to PCWP (rho -0.52, p<0.004) and extraction ratio correlated to oxygen-uptake efficiency slope (rho 0.40, p=0.029). Conclusions: In our diverse cohort, a significant proportion of Stage A/B patients reclassified to Stage C HFpEF via invasive exercise testing; abnormal peripheral profiles were also noted. Impaired cardiac and peripheral profile metrics were related to metabolic parameters. Broader implementation of iCPET in early disease stages and attention to both cardiac and peripheral profiles in diverse populations will guide further HFpEF research in novel mechanisms and therapeutics.

Reproducibility of cerebral blood flow, oxygen metabolism, and lactate and N-acetyl-aspartate concentrations measured using magnetic resonance imaging and spectroscopy.

In humans, resting cerebral perfusion, oxygen consumption and energy metabolism demonstrate large intersubject variation regardless of methodology. Whether a similar large variation is also present longitudinally in individual subjects is much less studied, but knowing the time variance in reproducibility is important when designing and interpreting longitudinal follow-up studies examining brain physiology. Therefore, we examined the reproducibility of cerebral blood flow (CBF), global cerebral metabolic rate of oxygen (CMRO2), global arteriovenous oxygen saturation difference (A-V.O2), and cerebral lactate and N-acetyl-aspartate (NAA) concentrations measured using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques through repeated measurements at 6h, 24h, 7days and several weeks after initial baseline measurements in young healthy adults (N = 26, 13 females, age range 18-35years). Using this setup, we calculated the correlation, limit of agreement (LoA) and within-subject coefficient of variation (CoVWS) between baseline values and the subsequent repeated measurements to examine the longitudinal variation in individual cerebral physiology. CBF and CMRO2 correlated significantly between baseline and all subsequent measurements. The strength of the correlations (R2) and reproducibility metrics (LoA and CoVWS) demonstrated the best reproducibility for the within-day measurements and generally declined with longer time between measurements. Cerebral lactate and NAA concentrations also correlated significantly for all measurements, except between baseline and the 7-day measurement for lactate. Similar to CBF and CMRO2, lactate and NAA demonstrated the best reproducibility for within-day repeated measurements. The gradual decline in reproducibility over time should be considered when designing and interpreting studies on brain physiology, for example, in the evaluation of treatment efficacy.

Prophylactic use of levosimendan in preoperative setting for surgical repair of congenital heart disease in children.

Low cardiac output syndrome (LCOS) is a significant cause of morbidity and the leading cause of mortality after pediatric cardiac surgery. Levosimendan has been shown safe and effective in pediatrics to treat LCOS. We aimed to review our local strategy with preoperative prophylactic Levosimendan infusion to minimize LCOS after heart surgery in identified high-risk patients. Retrospective monocentric study. As there is no reliable cardiac output measurement in children, we recorded hemodynamic parameters as surrogates of cardiac output after extracorporeal circulation through an electronic patient survey system at different time points. Seventy-two children received Levosimendan before surgery between 2010 and 2019. As expected, most patients were newborns and infants with prolonged open-heart surgeries. Median cardiopulmonary bypass time was 182 [137-234] min, and aortic clamping time was 95 [64-126] min. The postoperative hemodynamic parameters, vasoactive-inotropic score, and urine output remained stable throughout the first 48 h. Only a tiny portion of the patients had combined surrogate markers of LCOS with a maximal median arterial lactate of 2.6 [1.9-3.5] mmol/L during the first six postoperative hours, which then progressively normalized. The median arterio-venous difference in oxygen saturation was 31 [23-38] % between 12 and 18 h post-surgery and gradually decreased. The median venous-to-arterial CO2 difference was the highest at 10 [7-12] mmHg between 12 and 18 h post-surgery. Nine patients (13%) required extracorporeal membrane oxygenation. No patient required dialysis or hemofiltration. Mortality was 0%. Before congenital heart surgery, preoperative prophylactic administration of Levosimendan seems effective and safe for decreasing occurrence and duration of LCOS in high-risk children.

Correlation of venous to arterial carbon dioxide partial pressure difference with other cardiac output indices in patients undergoing intracardiac repair for tetralogy of fallot.

Clearance of tissue carbon dioxide by circulation is measured by venous to arterial carbon dioxide partial pressure difference (AVCO2) and is correlated with cardiac output (CO) in critically ill adult patients. This study aimed to correlate AVCO2 with other CO indices like arteriovenous oxygen saturation difference (AVO2), central venous oxygen saturation (ScVO2), and serum lactate in pediatric patients undergoing intracardiac repair (ICR) for tetralogy of Fallot (TOF). We conducted a prospective observational study in 50 patients, of age 5 months to 5 years, undergoing ICR for TOF and analyzed AVO2, AVCO2, ScVO2, and lactate from arterial and venous blood gas pairs obtained at different time intervals from admission to pediatric intensive care unit (PICU) (T0), at 6 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) postoperatively. Bivariate correlations were analyzed using Pearson for parametric variables. Admission AVCO2 was not correlated with AVO2 (R2 = 0.166, P = 0.246), ScVO2 (R2 = -2.2, P = 0.124), and lactate (R2 = -0.07, P = 0.624). At T1, AVCO2 was correlated with AVO2 (R2 = 0.283, P = 0.0464) but not with ScVO2 (R2 = - 0.25, P = 0.079) and lactate (R2 = -0.07, P = 0.623). At T2, T3 and T4, AVCO2 was correlated with AVO2 (R2 = 0.338,0.440 & 0.318, P = 0.0162, 0.0013, and 0.024), ScVO2 (R2 = - 0.344, - 0.488, and -0.366; P = 0.0143, <0.0001, and 0.017), and lactate (R2 = 0.305, 0.467 and 0.607; P = 0.0314, 0.00062 and <0.0001). AVCO2 was negatively correlated with ScVO2. No correlation observed between admission AVCO2 and mechanical ventilation duration. Two nonsurvivors had higher value of admission AVCO2 compared to survivors. AVCO2 is correlated with other CO surrogates like AVO2, ScVO2, and lactate in pediatric patients undergoing ICR for TOF.

Retinal blood flow and oxygen saturation in patients previously infected with COVID‐19

AbstractPurpose: The SARS‐CoV‐2 pandemic has affected all countries in the world and is still ongoing. Although respiratory symptoms are the main manifestation of acute infection, there is also increasing evidence that neurological and vascular symptoms occur, and it is unknown whether residuals remain after patients have recovered. We therefore set out to investigate whether ocular vascular alterations remain after patients have recovered.Methods: Patients that had recovered from COVID‐19 infection within the last 6 months before inclusion and healthy age‐ and sex‐matched controls were recruited. Main inclusion criteria for patients were confirmed positive PCR test for SARS‐CoV‐2 in the medical history and positive testing for SARS‐CoV‐2 seroprevalence while controls had no history of COVID‐19 infection. Arteriovenous (AV) difference in oxygen saturation was calculated out of retinal arterial and venous oxygen saturation, which were measured with a commercially available Dynamic Vessel Analyser (DVA, Imedos, Germany). Retinal vessel diameters and arteriovenous ratio (AVR) were assessed using the same device. In addition, mean blur rate in the tissue area of the optic nerve head (MT) was quantified using laser speckle flowgraphy (LSFG, Nidek, Japan).Results: 29 patients that had recovered from moderate to severe COVID‐19 requiring hospitalization (mean age 35 ± 17 years) and 11 control subjects (mean age 36 ± 12 years) were included in the present study. No differences between groups regarding sex or concomitant diseases in the medical history were found. Body mass index (BMI) was significantly higher in patients that had recovered from COVID‐19 (27.5 ± 5.6 vs. 24.5 ± 2.8 m2/kg, p = 0.036). AVR as well as AV difference in oxygen saturation was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). MT in the optic nerve head also was significantly lower in patients (23.4 ± 10.1 a.u.) than in control subjects (47.3 ± 26.6 a.u., p &lt; 0.001).Conclusions: The results of this study imply that retinal metabolism is still altered in patients after recovering from COVID‐19 infection. Longitudinal studies are required to investigate whether these changes in retinal vessels as well as optic nerve head blood flow are temporary or remain.

Retinal Oxygen Metabolism in Patients With Type 2 Diabetes and Different Stages of Diabetic Retinopathy.

The aim of this cross-sectional study was to assess retinal oxygen metabolism in patients with type 2 diabetes and different stages of nonproliferative diabetic retinopathy (DR) (n = 67) compared with healthy control subjects (n = 20). Thirty-four patients had no DR, 15 had mild DR, and 18 had moderate to severe DR. Retinal oxygen saturation in arteries and veins was measured using the oxygen module of a retinal vessel analyzer. Total retinal blood flow (TRBF) was measured using a custom-built Doppler optical coherence tomography system. Retinal oxygen extraction was calculated from retinal oxygen saturation and TRBF. Arteriovenous difference in oxygen saturation was highest in healthy subjects (34.9 ± 7.5%), followed by patients with no DR (32.5 ± 6.3%) and moderate to severe DR (30.3 ± 6.5%). The lowest values were found in patients with mild DR (27.3 ± 8.0%, P = 0.010 vs. healthy subjects). TRBF tended to be higher in patients with no DR (40.1 ± 9.2 μL/min) and mild DR (41.8 ± 15.0 μL/min) than in healthy subjects (37.2 ± 5.7 μL/min) and patients with moderate to severe DR (34.6 ± 10.4 μL/min). Retinal oxygen extraction was the highest in healthy subjects (2.24 ± 0.57 μL O2/min), followed by patients with no DR (2.14 ± 0.6 μL O2/min), mild DR (1.90 ± 0.77 μL O2/min), and moderate to severe DR (1.78 ± 0.57 μL O2/min, P = 0.040 vs. healthy subjects). These results indicate that retinal oxygen metabolism is altered in patients with type 2 diabetes. Furthermore, retinal oxygen extraction decreases with increasing severity of DR.

Acute uveitic phase of Vogt-Koyanagi-Harada disease: optic nerve head swelling, ocular blood flow and retinal oxygen metabolism.

To investigate the association of optic nerve head (ONH) swelling in the acute uveitic phase of Vogt-Koyanagi-Harada (VKH) disease with blood flow velocity in the choroid and ONH and oxygen saturation and diameter of retinal vessels. In this prospective study, 25 patients (50 eyes) were studied. Thirteen patients (26 eyes) had ONH swelling and 12 patients (24 eyes) had no ONH swelling. Laser speckle flowgraphy (LSFG) and retinal oximetry measurements were performed at presentation. In the ONH, mean blur rate (MBR)-vessel, representing blood flow velocity in retinal vessels, was significantly lower in the eyes affected by ONH swelling, while choroidal MBR was not significantly different. Eyes with ONH swelling had a significantly lower oxygen saturation in retinal venules, a significantly higher arteriovenous oxygen saturation difference and a significantly smaller calibre of retinal arterioles compared with eyes without ONH swelling. There were significant positive correlations between the MBR-vessel of the ONH and venular oxygen saturation and calibre of retinal arterioles. In addition, MBR-vessel of the ONH had a significant negative correlation with arteriovenous oxygen saturation difference. The occurrence of ONH swelling in the acute uveitic phase of VKH disease is associated with lower retinal blood flow velocity and smaller calibre of retinal arterioles as well as lower oxygen saturation in retinal venules and higher arteriovenous difference in oxygen saturation.

Changes in ocular blood flow and retinal oxygen metabolism during immunosuppressive therapy for initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

Purpose The aim of this study was to investigate the correlations between visual acuity, blood flow velocity in the choroid and optic nerve head (ONH) and oxygen saturation and calibre of retinal vessels during immunosuppressive therapy in patients with initial-onset acute uveitis associated with Vogt–Koyanagi–Harada (VKH) disease. Methods In this prospective study, 20 patients were studied. Laser speckle flowgraphy (LSFG) and retinal oximetry measurements were performed at baseline and at 4, 8 and 12 weeks after treatment. Results After immunosuppressive therapy, best-corrected visual acuity (BCVA) improved significantly at each post-treatment time-point compared with baseline value. Mean blur rate (MBR), representing blood flow velocity, in the choroid and ONH (overall and vessel areas) significantly increased. On the contrary, oxygen saturation of retinal arterioles and venules and calibre of retinal venules significantly decreased. There were significant negative correlations between ONH MBR vessel and arteriovenous oxygen saturation difference at baseline and at 4 weeks after treatment and between MBR tissue of the ONH and arteriovenous oxygen saturation difference at week 12 after treatment. Conclusions Immunosuppressive therapy in patients with initial-onset acute uveitis associated with VKH disease is associated with improved blood flow velocity in choroid and ONH and normalization of retinal oxygen metabolism and calibre of retinal venules. These correspond with improved visual acuity. These findings help explain the pathophysiology of VKH disease and its treatment and may provide biomarkers for choroiditis activity and response to treatment.

Veno-Arterial Partial Pressure of Carbon Dioxide Difference as a Metric of Systemic Oxygen Delivery: Insights from a Correlative Meta-Analysis

AbstractThe assessment of cardiac output and adequacy of systemic oxygen delivery in children after cardiac surgery require the use of an aggregate of hemodynamic monitors and blood tests. There are previously published data regarding the utility of the veno-arterial partial pressure of carbon dioxide difference (AVDco2) to help with this. This study pooled data on the correlation of AVDco2 with other metrics of cardiac output and systemic oxygen delivery such as arteriovenous oxygen saturation difference, venous saturation, and serum lactate. A systematic review of the literature was done to identify studies analyzing the correlation of AVDco2 with other hemodynamic and laboratory values. Data were extracted, and correlation coefficients were pooled for each specific comparison to create a point estimate for the overall correlation. A total of four studies with 350 patients and 809 paired blood gases were pooled. Adequate data were available to assess the correlation of AVDco2 with arteriovenous oxygen saturation difference, venous saturation, and serum lactate. There was a significant, moderate correlation with arteriovenous oxygen saturation difference and venous saturation. A significant, weak correlation with serum lactate was found. The AVDco2 has significant, moderate correlations with other metrics of the adequacy of systemic oxygen delivery such as arteriovenous oxygen saturation difference and venous saturation. There was a significant but only weak correlation with serum lactate. AVDco2 may be complementary to assess the adequacy of cardiac output and systemic oxygen delivery.

This issue of ACTA, printed and electronic

This issue of ACTA, printed and electronic

Retinal oxygen saturation and vessel diameter in patients with chronic kidney disease.

To investigate changes in retinal oximetry and the diameter of retinal vasculature in patients with chronic kidney disease (CKD) and relationships between retinal vasculature and the estimated glomerular filtration rate (eGFR), provide a scientific basis for the early detection and diagnosis of CKD. Eighty-three patients with CKD and 103 healthy individuals were included after providing informed consent. All participants were examined using a noninvasive technology (Oxymap Inc., Reykjavik, Iceland) for measuring the arterial (SaO2 ) and venous (SvO2 ) oxygen saturation and the arteriovenous difference in oxygen saturation (Sa-vO2 ). The corresponding retinal vessel diameters of these arterioles (D-A) and venules (D-V) were measured. The eGFR of patients with CKD was calculated from the serum creatinine concentration. In general, patients with CKD had higher mean SaO2 values than healthy individuals (100.15±4.68% versus 97.14±4.22%; p<0.001, mean±SD). The mean SaO2 in the superior temporal, superior nasal and inferior nasal quadrants significantly increased. There was no significant difference measured in the SvO2 when patients with CKD (63.66±5.29%) and healthy individuals (62.70±5.27%) were compared. The mean Sa-vO2 of the CKD group (36.49±4.98%) was increased compared with normal subjects (34.44±4.76%) (p=0.005). The retinal arteriole diameter was narrower in patients with CKD than in normal individuals (117.53±14.88μm versus 126.87±14.98μm; p<0.001, mean±SD), and the arteriovenous ratio was smaller than in normal individuals (0.71±0.09 versus 0.77±0.09; p<0.001, mean±SD). Pearson's two-tailed correlation showed a significant correlation between the SaO2 and eGFR (R=-0.363, p=0.001), and narrower retinal arterial calibre was significantly associated with a lower eGFR (R=0.415, p<0.001). Based on our results, there were alterations in retinal oxygen saturation and vascular diameter in patients with CKD. Further studies are needed to determine whether such changes play a role in the development of CKD.

Anatomical and functional changes in the retina in patients with Alzheimer's disease and mild cognitive impairment.

PurposeThere is evidence that mild cognitive impairment (MCI) or Alzheimer's disease (AD) is accompanied by alterations in the retina. The current study was performed to investigate structural and functional changes in patients with systemic neurodegenerative disease.MethodsA total of 47 patients with either MCI or AD and 43 healthy age‐ and sex‐matched control subjects were included. Inclusion criteria for MCI were abnormal memory function and a mini‐mental state examination (MMSE) score >26 points, for patients with AD a diagnosis of probable AD of mild to moderate degree and an MMSE score in the range of 20–26. Retinal blood flow was measured using a Doppler optical coherence tomography (OCT) system. Retinal vessel diameter, oxygen saturation and flicker‐induced vasodilatation were measured using a Vessel Analyzer. Retinal nerve fibre layer thickness (RNFLT) was assessed using an OCT system.ResultsGlobal RNFLT was lower in patients compared to healthy controls (93.7 ± 12.8 µm versus 99.1 ± 9.0 µm, p = 0.02). The same was found in regards to retinal arterial blood flow, which was 9.3 ± 2.4 and 12.3 ± 3.2 μl/min in the patient and control groups, respectively (p < 0.001). Mean retinal arterial diameter was reduced in patients (76.0 ± 8.9 µm versus 80.6 ± 8.0 µm, p = 0.03). Arteriovenous difference in oxygen saturation was lower in patients (20.4 ± 5.1% versus 23.5 ± 4.0%, p < 0.01). No difference in the flicker response was observed.ConclusionIn patients with MCI and AD, arteriovenous difference in oxygen saturation, retinal blood flow and arterial vessel diameter was reduced. No difference was found in flicker response between groups. This indicates alterations in retinal oxygen metabolism in patients with neurodegenerative disease.

Short-time effect of intravitreal injections on retinal vascular oxygenation and vessel diameter in patients with diabetic macular oedema or neovascular age-related macular degeneration.

PurposeTo investigate the short‐time effect of intravitreal injections (IVI) of the vascular endothelial growth factor inhibitors ranibizumab and aflibercept on retinal arterial and venous oxygen saturation (SO2a and SO2v), arteriovenous oxygen saturation difference (AVD) and vessel diameter (VDa and VDv) in patients with diabetic macular oedema (DME) and patients with choroidal neovascularization (CNV) due to age‐related macular degeneration.MethodsUncontrolled prospective observational study in 100 eyes. Retinal vessel oxygen saturation and diameters were assessed using a retinal oximeter before and minutes after IVI of ranibizumab or aflibercept.Results40 eyes with CNV and 34 eyes with DME were included in the analysis. At baseline, SO2a and SO2v were significantly higher in DME (p = 0.043 and p = 0.009, respectively). After IVI, SO2a significantly decreased in CNV and DME eyes by 2.6% (p = 0.016) and 4.6% (p = 0.002) and SO2v decreased by 14.0% (p = 0.004) and 12.4% (p = 0.017), respectively. However, a significant increase in AVD was only found in CNV (15.7%, p = 0.001). VDa decreased significantly only in DME by 5.7% (p = 0.010). No medication‐specific disease effect was found and vice versa.ConclusionsThe observed changes can be interpreted as signs of increased metabolic demand during the physiological stress after an IVI. The abnormal arterial constriction and the abolished increase in AVD seen only in eyes with DME indicate an impairment of vascular autoregulation and oxygen distribution and a reduced neuroretinal metabolism in the diabetic retina with a significant impact on inner retinal oxygen consumption shortly after IVI.

This Issue of Acta

This Issue of Acta

This issue of Acta

This issue of Acta

Reduced Cerebral Metabolic Rate of Oxygen in Adults with Sickle Cell Disease

Introduction:Cerebral blood flow (CBF) is increased in sickle cell disease (SCD) to compensate for chronic hemolytic anemia. Since the brain is strongly dependent on adequate oxygen levels, severe anemia may result in ischemia and silent cerebral infarctions (SCIs), which are present in the majority of patients with SCD. Besides CBF, the cerebral metabolic rate of oxygen (CMRO2), representing the cerebral oxygen consumption, can be measured using specialized MRI techniques. CMRO2 is dependent on CBF, OEF oxygen extraction fraction (OEF) and the hematocrit in the cerebral circulation. In order to maintain stable CMRO2 the OEF changes to compensate for fluctuations in CBF. Previous studies found either elevated or reduced rather than stable CMRO2 in SCD. To further explore the regulation of cerebral oxygenation in SCD, we measured CMRO2, OEF and CBF using MRI at rest and upon administration of acetazolamide (ACZ), a non-metabolic vasodilator. In addition, we related the CMRO2 to the prevalence and location of SCIs and to laboratory parameters of hemolysis.Methods:Adult SCD patients (HbSS/HbSβ0) without a history of stroke, and healthy age-, sex, and race-matched controls were recruited for this IRB-approved MRI study with ACZ-induced vasodilation and venous blood sampling. MRI images were acquired at 3T (Philips Healthcare, Best, NL). Sequences included 3D FLAIR with 1mm isotropic resolution for lesion evaluation, longitudinal and transverse relaxation times of blood (T1b and T2b) in the cerebral sagittal sinus using a T2 prepared tissue relaxation with inversion recovery sequence (T2-TRIR), and pseudo-continuous arterial spin labeling (ASL) for whole brain CBF measurements. T1b was used to correct ASL-based CBF values. T2b was converted to venous saturation (Yv) using a recently published SCD-specific model, which was calibrated in sickle blood rather than bovine blood. CBF was measured at baseline and 10 min post acetazolamide (ACZ) (16mg/kg intravenous infusion over 3min). Images were co-registered and quantified using the ExploreASL toolbox.CMRO2 was calculated as follows: CMRO2 = CBF * OEF * Ca, where CBF is the whole brain CBF map from ASL, OEF is the arteriovenous oxygen saturation (Y) difference (Ya-Yv/Ya) derived from T2 measurements, and Ca is the oxygen carrying capacity of blood calculated from hematocrit sampled immediately prior to MRI. Blood markers of hemolysis (reticulocyte count and bilirubin) were correlated to MRI hemodynamic markers using bivariate Spearman's rho (ρ). Group comparisons were tested using Student's t-tests. P values <0.05 were considered statistically significant.Results:As expected, CBF was significantly higher in patients with SCD (69 ± 16 mL/100g/min) compared to healthy controls (42 ± 4 mL/100g/min, P <0.001), whereas oxygen carrying capacity (Ca) was significantly lower in patients with SCD vs healthy controls due to lower hematocrit (485 ± 83 vs 794 ± 66 μmol O2/100ml blood, P=0.001). At baseline, mean CMRO2 was lower in patients with SCD compared to healthy controls (88 ± 20 vs 117 ± 18 μmol/100 g/min, P = 0.002), contrary to our hypothesis, indicating a reduced oxygen metabolism in patients with SCD. After acetazolamide, CMRO2 remained the same due to an increase in CBF (P<0.001) and a compensatory reduction in OEF. The reduction in OEF in patients with SCD and healthy controls (20 ± 7 vs 19 ± 6, respectively P= 0.76) indicates that OEF adjusts appropriately according to the increased flow. By mapping CMRO2 and the locations of SCIs, we found that lesions were most prevalent in the regions with the lowest CMRO2 corresponding to the deep white matter and borderzone regions, supporting an ischemic etiology of lesions. High hemolytic rate was associated with higher CMRO2 most likely due to an increased CBF.Conclusion:We observed reduced CMRO2 in patients with SCD compared to healthy controls due to low OEF. A reduced CMRO2 could pose a risk for ischemia, despite high flow rate delivering oxygen, because of low OEF. This is supported by the fact that the silent cerebral infarcts are located in regions with the lowest CMRO2. We postulate that patients with SCD have a reduced capacity to increase the OEF in regions with inadequate CBF resulting in local ischemia and local infarction. The pathogenesis of the reduced OEF remains unclear but could be related to arteriovenous shunting whereby there is insufficient time for oxygen to dissociate. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Retinal oxygen saturation as a non-invasive estimate for mixed venous oxygen saturation and cardiac output.

To investigate the correlation between retinal vessel oxygen saturation and mixed venous oxygen saturation (SvO2-mixed ) and cardiac output (CO). Retinal arterial (SaO2-retinal ) and venous (SvO2-retinal ) oxygen saturation were measured non-invasively with dual-wavelength retinal oximetry in subjects receiving invasive measurements of SvO2-mixed and CO through right heart catheterization. Correlations were analysed using Spearman's rank correlation coefficients and linear regression models. Fourteen patients (median age 62.7years, range: 21-77) were included in the analysis. When adjusted for age, SvO2-retinal showed a positive correlation with SvO2-mixed (β=0.80, p=0.003). Retinal arteriovenous oxygen saturation difference was significantly correlated with the inverse of CO (Spearman's ρ=0.59, p=0.026). This pilot study provides proof of concept for the use of retinal oximetry as a non-invasive tool to assess systemic cardiovascular function.

Improved discrimination between normal-tension and primary open-angle glaucoma with advanced vascular examinations - the Leuven Eye Study.

Vascular factors have been suggested to influence the development and progression of glaucoma. They are thought to be especially relevant for normal-tension glaucoma (NTG) patients. We aim to investigate which vascular factors, including advanced vascular examinations, better describe patients with NTG comparing to those with primary open-angle glaucoma (POAG). The Leuven Eye Study database (182 NTG and 202 POAG patients; similar structural and functional damage) was used to compute three multivariate logistic regression models: a conventional model (conventional parameters only, including vascular-related self-reported phenomena, such as migraine or peripheral vasospasm); an advanced vascular model (advanced vascular parameters only: colour Doppler imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness); and a global model, in which both types of parameters were allowed. Receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUC) were calculated and compared between models. Patients with NTG had a higher resistive index and lower early systolic acceleration (ESA) in their retrobulbar vessels and a smaller arteriovenous retinal oxygen saturation difference. The global model (AUC 0.743) showed a significantly better discriminative ability when compared to either the conventional (AUC 0.687, p=0.049) or the advanced vascular (AUC 0.677, p=0.005) models. Also, the conventional and the advanced vascular models showed a similar discriminative ability (p=0.823). Patients with NTG have more signs of vascular dysfunction. Clinical conventional parameters, such as asking simple vascular-related questions, combined with advanced vascular examinations provide information to better understand the value that non-IOP-related factors play in NTG.