Absolute retinal blood flow in healthy eyes and in eyes with retinal vein occlusion.

PURPOSE: To measure non-invasively retinal venous blood flow (RBF) in healthy subjects and patients with retinal venous occlusion (RVO). METHODS: The prototype named AO-LDV (Adaptive Optics Laser Doppler Velocimeter), which combines a new absolute laser Doppler velocimeter with an adaptive optics fundus camera (rtx1, Imagine Eyes®, Orsay, France), was studied for the measurement of absolute RBF as a function of retinal vessel diameters and simultaneous measurement of red blood cell velocity. RBF was measured in healthy subjects (n = 15) and patients with retinal venous occlusion (RVO, n = 6). We also evaluated two softwares for the measurement of retinal vessel diameters: software 1 (automatic vessel detection, profile analysis) and software 2 (based on the use of deep neural networks for semantic segmentation of vessels, using a M2u-Net architecture). RESULTS: Software 2 provided a higher rate of automatic retinal vessel measurement (99.5 % of 12,320 AO images) than software 1 (64.9 %) and wider measurements (75.5 ± 15.7 µm vs 70.9 ± 19.8 µm, p < 0.001). For healthy subjects (n = 15), all the retinal veins in one eye were measured to obtain the total RBF. In healthy subjects, the total RBF was 37.8 ± 6.8 µl/min. There was a significant linear correlation between retinal vessel diameter and maximal velocity (slope = 0.1016; p < 0.001; r2 = 0.8597) and a significant power curve correlation between retinal vessel diameter and blood flow (3.63 × 10-5 × D2.54; p < 0.001; r2 = 0.7287). No significant relationship was found between total RBF and systolic and diastolic blood pressure, ocular perfusion pressure, heart rate, or hematocrit. For RVO patients (n = 6), a significant decrease in RBF was noted in occluded veins (3.51 ± 2.25 µl/min) compared with the contralateral healthy eye (11.07 ± 4.53 µl/min). For occluded vessels, the slope between diameter and velocity was 0.0195 (p < 0.001; r2 = 0.6068) and the relation between diameter and flow was Q = 9.91 × 10-6 × D2.41 (p < 0.01; r2 = 0.2526). CONCLUSION: This AO-LDV prototype offers new opportunity to study RBF in humans and to evaluate treatment in retinal vein diseases.

Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

Vasoreactivity of the optic nerve head, nailfold, and facial skin in response to cold provocation in normal-tension glaucoma patients.

BACKGROUND: The dysfunction of optic nerve head (ONH) hemodynamics has been suggested to be involved in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to compare vasoreactivity in the ONH, nailfold, and facial skin in response to cold-water provocation in NTG patients and healthy controls. METHODS: We performed cold-water provocation in 14 eyes of 14 NTG patients and 15 eyes of 15 age-matched control subjects. Laser speckle flowgraphy-derived tissue-area mean blur rate (MT), skin blood flowmetry-derived pulse wave amplitude (PA), nailfold capillaroscopy-derived nailfold capillary diameter, and other clinical parameters were recorded at baseline and 4 and 6 min after the cold stimulus. We compared changes (as percentages) in these variables in the NTG and control subjects with a linear mixed-effects model and evaluated correlations between these changes with Spearman's rank correlation coefficient. RESULTS: The interaction term between the NTG group (reference, control group) and the 4-min protocol step (reference, baseline) significantly affected the changes in MT, nailfold capillary diameter and PA (ß = -9.51%, P = 0.017, ß = -20.32%, P = 0.002; ß = + 18.06%, P = 0.017, respectively). The change in MT was positively correlated with the change in nailfold capillary diameter, and negatively correlated with the change in PA (r = 0.39, P = 0.036; r = -0.40, P = 0.031, respectively). CONCLUSION: NTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation.

A comprehensive update on the use of optical coherence tomography angiography in glaucoma.

PURPOSE: The primary purpose of this review is to provide a comprehensive summary on the technical principles of OCTA and to enumerate vascular parameters being explicated for glaucoma diagnosis and progression with emphasis on recent studies. In addition, the authors also summarize the future clinical potentials of OCTA in glaucoma and enumerate the limitations of this imaging modality in the present-day scenario. METHODS: The index study is a narrative review on OCTA in glaucoma. The authors searched the PubMed database using the key phrases ''optical coherence tomography angiography" AND "glaucoma,'' AND/OR "vascular parameters" AND/OR "ocular perfusion." Being a relatively recent development in ocular imaging, studies in which OCTA imaging had been used for glaucoma evaluation since 2012 were included until March 2022. The literature search included original studies and previous review articles, while case reports were excluded. Preliminary search was based on relevant articles with search keywords in the title and abstract. The second screening was performed by reading the full text of the literature. RESULTS: Recent studies indicate reduction in microcirculation in glaucomatous eyes compared to the normal subjects. The area of interest for glaucoma evaluation using OCTA varies among the different studies. Based on the literature reviewed here, (1) OCTA parameters measured in the peripapillary; ONH and macular area have been shown to differentiate between glaucoma and normal eyes with a discriminatory power comparable to OCT parameters used routinely in clinics, (2) monitoring of peripapillary and macular vessel density may provide important information to the evaluation of glaucoma progression and prediction of rates of disease worsening, (3) studies suggest strong correlation between the OCTA parameters, the OCT parameters and visual function, measured by visual field testing, in glaucomatous eyes, (4) future prospects of OCTA in glaucoma evaluations using AI predicting structural and functional features and prognosis based on early vascular findings would open up scope for early detection of high-risk suspects and fast progressors in glaucoma. CONCLUSION: OCTA can be useful in quantifying vascular parameters in the optic disc, peripapillary and the macular regions for glaucoma evaluation. OCTA shows potential to become a part of everyday glaucoma management.

A meta-analysis of variability in conjunctival microvascular hemorheology metrics.

Conjunctival hemorheology has been used analytically to assess qualities of blood flow associated with various forms of cardiovascular disorders including diabetes mellitus, stroke, and sickle cell disease. Although conjunctival axial red blood cell velocity (Vax) has been demonstrated in varying disease states, benchmark measures of Vax are not well-defined. Due to various methodologic differences in assessment of Vax, interstudy consistency of hemorheological metrics is susceptible to both systematic and random error. Our study examines interstudy heterogeneity of Vax as measured in the conjunctival microvasculature of healthy subjects and assesses the overall perturbation of Vax based on disease state. Furthermore, our study aims to establish a potential range of normative Vax by comparing inter-study measurements in healthy patients. The most widely employed analytic approach to assess Vax was space-time analysis (n = 30). Using a meta-analytic approach, the prediction interval for Vax in healthy subjects among 20 studies ranged from 0.32-2.60 mm/s with a combined effect size of 0.52 ± 0.03 (CI: 0.46-0.59) mm/s. Inter-study comparison of Vax in healthy patients showed a high degree of variability (I2: 98.96%), due to studies with low measurement precision and/or dissimilar analytic methodology. Neither age nor diameter was a clinically significant moderator of Vax measurements in healthy patients. The combined effect size, defined as the composite Hedge's g of studies comparing healthy and disease state mean Vax, was 0.21 ± 0.13. High heterogeneity (I2: 80.48%) was observed in studies analyzing the difference between mean Vax in healthy and disease state patients. This heterogeneity was also observed when the difference in mean Vax between healthy and disease state patients was assessed in subgroups based on disease condition (I2: vascular disease 33%, sickle cell disease 62.22%, other 83.43%). Age was found to be a significant moderator (p = 0.048, ß = -0.40) of Hedge's g while diameter was not. No significant publication bias was observed in studies presenting healthy patient Vax or in studies comparing Vax between healthy and disease state patients. In summary, although homogeneity can be seen in healthy group Vax measurements, a high degree of statistical heterogeneity is found in Vax assessment comparing healthy and disease conditions that is not fully explained by methodologic variability.

Retrobulbar blood flow velocity in systemic lupus erythematosus assessed by color Doppler imaging.

OBJECTIVE: To analyze the blood flow in retrobulbar vessels in systemic lupus erythematosus (SLE) by color Doppler imaging (CDI) and to investigate the associations between immunological markers, retinal abnormalities, disease activity, and vascular parameters. METHODS: We examined 30 patients with SLE who were aged 32.1 ± 11.6 years with a disease duration of 68.0 ± 55.6 months and 30 participants in a control group. The peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI) of the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs) were determined. Physical and ophthalmic examinations with assessments of immunological markers were performed. All parameters were compared between SLE patients and normal controls while the correlations among parameters were analyzed. RESULTS: In the SLE group, CDI confirmed blood flow abnormalities in the CRA and PCAs, with significantly lower blood flow velocities and increased RI and PI (p < 0.05). There was a significantly negative correlation between disease duration and EDV in the CRA, PCA, and OA (p = 0.0423, 0.0453, 0.0448). There was also a significant relationship between the SLE Disease Activity Index and the PI of the OA (p = 0.0367). The patients who had received biological agents (Rituximab) had lower EDV in the CRA and PCA (p = 0.0026, 0.028). SLE patients with kidney or CNS involvement had a significant increase in the PI in the OA (p = 0.0287). The PSV and EDV in the CRA were significantly related to creatinine (p = 0.0007 and 0.0418). We also noted a significant decreased EDV in the CRA and an increased RI in the OA among participants positive for anti-dsDNA antibodies (p = 0.0331 and 0.0228). CONCLUSIONS: Retrobulbar circulatory disturbances were detected in SLE patients by CDI. These findings seem likely to affect smaller vessels like the CRA and PCA. However, the presence of measurable changes in the OA is generally indicative of a coexistent nephropathy or central nervous system (CNS) vasculitis. Creatinine, the disease activity index, being positive for anti-dsDNA, and receiving biological agents were associated with measurable changes on the retrobulbar blood flow.

Ocular blood flow and choroidal thickness in ocular hypertension.

PURPOSE: Ocular hypertension (OHT) is a clinical entity characterized by elevated intraocular pressure (IOP) without optic nerve damage. In the presence of other risk factors, OHT may progress to glaucoma. This study aimed to evaluate ocular blood flow (OBF) and choroidal thickness (CT), which may be markers and/or risk factors that could assess the progression of OHT to glaucoma. MATERIAL AND METHODS: Age and gender matched 60 eyes of 32 patients with OHT and 61 eyes of 31 control patients were included for this study. All participants underwent a detailed ophthalmological examination including best-corrected visual acuity, IOP measurement with Goldmann applanation tonometry, gonioscopy, optic nerve evaluation with 78 D lens, and visual field test with Humphrey visual field analyzer. Retinal nerve fiber layer, ganglion cell complex, and central corneal thickness measurements were performed by optical coherence tomography (OCT). CT was measured with OCT in the fovea, 1.5 mm, 2 mm, 2.5 mm nasal and temporal to the fovea and from nasal and temporal to the optic disk. OBF data including peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI) and pulsatility index (PI) were measured with color Doppler imaging (CDI) from the ophthalmic artery (OA), central retinal artery (CRA), medial and lateral branches of short posterior ciliary arteries (MPCA, LPCA). Systolic (SBP) and diastolic arterial blood pressure were also noted. RESULTS: CT measurement at each point in the OHT group compared to the control group were found to be significantly thinner (p = 0.001). There was a decrement in CT from the fovea to the nasal and temporal retina in both groups. In the OHT group, there was a significant decrease in PSV and EDV of OA, CRA, MPCA, and LPCA, and a significant increase in PI and RI of measured arteries. (EDV p = 0.036, PI p = 0.006, RI p = 0.006 for OA and p = 0.001 for other arteries and all OBF measurements). There was a negative correlation between CT and age, IOP and axial length (AL) in OHT group (r = - 0.529, p = 0.001; r = - 0.258, p = 0.047; r = - 0.345, p = 0.007, respectively, for fovea). But there was no statistically significant correlation between CT and other measurements in the control group, except age (r = - 0.860 p = 0.001 for fovea). CONCLUSION: We found that OBF decrement and choroidal thinning in OHT group compared with controls. Interpretation both of CT measurements with OCT and OBF parameters with CDI and new imaging technologies may help to prevent and reduce the possible optic nerve damage.

[Changes in ocular hemodynamics in patients recovered from COVID-19]. / Oftal'mogemodinamicheskie narusheniya posle perenesennoi koronavirusnoi infektsii, vyzvannoi virusom SARS-CoV-2.

PURPOSE: To evaluate the severity of hemodynamic changes in the ocular vessels of patients recovered from COVID-19. MATERIAL AND METHODS: The study included 44 patients (88 eyes) aged 28-60 years, among them 24 (54.5%) women and 20 (45.4%) men, with SARS-CoV-2 infection confirmed by PCR no more than 2 months prior to enrollment and with no ophthalmological complaints within 2 months before the disease, as well as 20 healthy volunteers (40 eyes). At the time of the study all patients had a negative PCR result for SARS-CoV-2. The patients were divided into 2 groups. The first group comprised 24 patients who did not take any anticoagulants during the treatment. The second group consisted of 20 patients who received anticoagulants (Rivaroxaban (Xarelto)) at a dosage of 10 mg per day for 1-1.5 months. The maximum systolic (Vs), end-diastolic (Vd) blood flow velocity, as well as resistance index (RI) in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCA) were measured in all study patients with the ultrasound imaging system VOLUSON E8 Expert («Kretz¼, USA). Additionally, the flowmetry method was used to assess the volumetric ocular blood flow (VOBF) on Ocular Blood Flow Analyzer system («Paradigm Medical Industries, Inc.¼, USA). RESULTS: In the first group, a decrease in Vs and Vd was noted amid a significant increase of RI in CRA and SPCA, as well as an increase of RI in OA compared with the age-normal values (p<0.05). In the second group, a decrease in Vs and Vd was noted amid a significant increase of RI in CRA, as well as a decrease in Vs in SPCA and an increase of RI in OA relative to the age-normal values (p<0.05). A decrease in VOBF was noted in the first group in comparison to the second group and the age norm (p<0.05). CONCLUSION: Blood flow velocity parameters in the ocular vessels are reduced in patients recovered from COVID-19 compared to the age-normal values. There was a significant decrease in volumetric ocular blood flow parameters in COVID-19 patients who did not take any anticoagulants compared to the age-normal values. Anticoagulants intake has a positive impact on hemodynamic characteristics in the ocular vessels and volumetric ocular blood flow in patients with COVID-19.

Time-Course Changes in Optic Nerve Head Blood Flow and Retinal Nerve Fiber Layer Thickness in Eyes with Open-angle Glaucoma.

PURPOSE: To determine whether decreased optic nerve head (ONH) blood flow (BF) precedes or follows decreased circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in eyes with open-angle glaucoma (OAG). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: This study followed up 350 eyes of 225 OAG patients for at least 2 years and collected data from each patient from at least 5 examinations obtained with laser speckle flowgraphy (LSFG) and OCT. METHODS: In the superior, temporal, and inferior ONH quadrants, tissue area mean blur rate (MT), representing ONH tissue BF, was measured with LSFG, whereas cpRNFLT was measured with OCT. A multivariate linear mixed-effects model was used to identify potential predictors of faster MT decrease, adjusting for possible confounding factors. Based on these results, each quadrant of each patient was assigned a risk point if the quadrant was the superior or temporal, if patient age was older than the median (61 years), and if patient pulse rate was higher than median (74 beats per minute). The quadrants were then compared with a mixed-effects Cox model for MT and cpRNFLT changes, defined as a difference between the baseline value and the values from the latest 2 consecutive follow-up visits of more than 1.96 × the corresponding coefficient of variation. MAIN OUTCOME MEASURES: Ophthalmic and systemic variables and MT and cpRNFLT in the superior, temporal, and inferior quadrants. RESULTS: The multivariate model showed that MT decrease was faster in older patients with higher pulse rate and slower in inferior quadrants (P < 0.05). Quadrants with 0 risk points showed primary cpRNFLT decrease (P = 0.048), 1-risk point quadrants showed simultaneous cpRNFLT and MT decrease (P = 0.260), and 2-risk point and 3-risk point quadrants showed primary MT decrease (P < 0.001). CONCLUSIONS: Older patients with higher pulse rate are at greater risk of a primary reduction in ONH tissue BF, that is, preceding cpRNFLT decrease, in the superior and temporal quadrants.

Ocular Blood Flow Measurements in Diabetic Retinopathy Using 3D Pseudocontinuous Arterial Spin Labeling.

BACKGROUND: Distinguishing between the two broad categories of diabetic retinopathy (DR), nonproliferative DR (NPDR) and proliferative DR (PDR), is significant, as the therapeutic strategies for each are completely different. PURPOSE: To characterize the ocular blood flow (OBF) of DR patients and evaluate the potential utility of OBF values in categorizing DR. STUDY TYPE: Prospective. SUBJECTS: A total of 41 DR patients (82 eyes) were recruited in our study. Group 1 comprised 48 eyes with NPDR, and Group 2 comprised 34 eyes with PDR. FIELD STRENGTH/SEQUENCE: 3D pseudocontinuous arterial spin labeling (3D-pcASL) with two postlabeling delays (PLDs) was acquired at 3.0T MR. ASSESSMENT: OBF values were independently obtained by two doctors from the OBF map. STATISTICAL TESTS: OBF values and clinical characteristics were compared between the groups using two-sample t-tests and chi-square tests. Receiver operating characteristic (ROC) curves were obtained, and the area under the curve (AUC) was calculated. The consistency of OBF values reported by the two doctors was evaluated using the intraclass correlation coefficient (ICC). RESULTS: OBF values at PLDs of 1.5 seconds and 2.5 seconds were significantly lower in Group 2 than in Group 1 (P < 0.05 for both PLDs). The OBF values of Group 2 showed a greater increase than those of Group 1 from PLD 1.5 to 2.5 seconds. The AUC of OBF at the 1.5 seconds PLD was 0.90, with a cutoff of 7.73 mL/min/100 g, and the AUC of the OBF at the 2.5 seconds PLD was 0.75, with a cutoff of 8.44 mL/min/100 g. The ICC between the two observers was 0.844 for the OBF at 1.5 seconds PLD and 0.872 for the OBF at 2.5 seconds PLD. DATA CONCLUSION: PDR can be differentiated from NPDR by the value of OBF as measured by 3D-pcASL. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Association of ocular blood flow and contrast sensitivity in normal tension glaucoma.

PURPOSE: To investigate the relationship of ocular blood flow (via arteriovenous passage time, AVP) and contrast sensitivity (CS) in healthy as well as normal tension glaucoma (NTG) subjects. DESIGN: Mono-center comparative prospective trial METHODS: Twenty-five NTG patients without medication and 25 healthy test participants were recruited. AVP as a measure of retinal blood flow was recorded via fluorescein angiography after CS measurement using digital image analysis. Association of AVP and CS at 4 spatial frequencies (3, 6, 12, and 18 cycles per degree, cpd) was explored with correlation analysis. RESULTS: Significant differences regarding AVP, visual field defect, intraocular pressure, and CS measurement were recorded in-between the control group and NTG patients. In NTG patients, AVP was significantly correlated to CS at all investigated cpd (3 cpd: r = - 0.432, p< 0.03; 6 cpd: r = - 0.629, p< 0.0005; 12 cpd: r = - 0.535, p< 0.005; and 18 cpd: r = - 0.58, p< 0.001), whereas no significant correlations were found in the control group. Visual acuity was significantly correlated to CS at 6, 12, and 18 cpd in NTG patients (r = - 0.68, p< 0.002; r = - 0.54, p< .02, and r = - 0.88, p< 0.0001 respectively), however not in healthy control patients. Age, visual field defect MD, and PSD were not significantly correlated to CS in in the NTG group. MD and PSD were significantly correlated to CS at 3 cpd in healthy eyes (r = 0.55, p< 0.02; r = - 0.47, p< 0.03). CONCLUSION: Retinal blood flow alterations show a relationship with contrast sensitivity loss in NTG patients. This might reflect a disease-related link between retinal blood flow and visual function. This association was not recorded in healthy volunteers.

Quantitative evaluation of retinal microvasculature and retrobulbar vessels after intravenous chemotherapy for retinoblastoma.

BACKGROUD: To evaluate the changes in retinal microvasculature and retrobulbar blood flow, using optical coherence tomography angiography (OCTA) and Color Doppler imaging (CDI) after intravenous chemotherapy (IVC) in patients with retinoblastoma (RB). METHODS: This was a retrospective comparative case control series involving 30 patients. Ten bilateral RB patients that had a preserved eye with extramacular tumours (group I), 10 unilateral RB treated with IVC that had a normal fellow study eye (group II), and 10 age-matched healthy controls. The macular retinal thickness, foveal avascular zone (FAZ) area, and the macular and peripapillary retinal vessel densities (RVD) were measured. The peak systolic and end diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. A comparison among the three groups was conducted. RESULTS: Between the three cohorts, OCTA revealed no significant difference in FAZ area, superficial foveal and parafoveal RVD, deep parafoveal RVD and peripapillary RVD, (P > 0.05). By contrast, the mean deep foveal RVD, the full, inner and outer foveal and the parafoveal retinal thickness were significantly lower in group I compared with the controls, (P = 0.0329, 0.0153, 0.0311 0.0352, 0.0215). No significant difference in the blood flow velocities occurred in the retrobulbar circulation (P > 0.05). CONCLUSIONS: In patients with retinoblastoma, OCTA did not detect significant changes of retinal thickness and vessel density in the eyes treated with IVC, but a slight reduction in retinal thickness and the deep foveal RVD seemed to occur in bilateral RB eyes. The retrobulbar blood flow parameters showed no measurable changes.

Assessment of ocular blood flow in continuous-flow ventricular assist device by laser speckle flowgraphy.

Although the influence of continuous-flow left ventricular assist device (CF-LVAD) support on peripheral circulation has been widely discussed, its monitoring modalities are limited. The aim of this study was to assess the peripheral circulation using the laser speckle flowgraph (LSFG) which can quantitatively measure the ocular blood flow. We implanted a centrifugal CF-LVAD (EVAHEART®; Sun Medical Technology Research Corporation, Nagano, Japan) in five adult goats (body weight 44.5 ± 2.9 kg) under general anesthesia. The waveform of the central retinal artery using the mean blur rate (MBR) for ocular blood velocity and fluctuations as a parameter of pulsatility were obtained before LVAD implantation and after LVAD full-bypass support. The MBR waveform and LSFG fluctuation data were compared with the waveform and pulsatility index of the external carotid artery using an ultrasonic flow meter to evaluate circulatory patterns at different levels. The MBR waveform pattern of the central retinal artery was pulsatile before LVAD implantation and less pulsatile under LVAD full bypass. The fluctuation was 14.7 ± 1.86 before LVAD implantation and 3.85 ± 0.61 under LVAD full bypass (p < 0.01), respectively. The fluctuations of LSFG showed a strong correlation with the pulsatility index of the external carotid artery meaning that similar changes in circulatory pattern were observed at two different levels. Measuring the ocular blood flow using LSFG has potential utility for the assessment of the status of the peripheral circulation and its pulsatility during CF-LVAD.

Carotid endarterectomy restores decreased vision due to chronic ocular ischemia.

BACKGROUND: The therapeutic effect of carotid endarterectomy (CEA) on visual disturbance caused by chronic ocular ischemia due to carotid artery stenosis has not been validated. This prospective observational study aims to investigate whether CEA is associated with an increase in ocular blood flow (OBF) and postoperative visual improvement. METHODS: In total, 41 patients with carotid artery stenosis treated by CEA between March 2015 and September 2018 were enrolled in this study. OBF was evaluated by laser speckle flowgraphy, which can measure the mean blur ratio (MBR) which is well correlated to the absolute retinal blood flow. Visual acuity was assessed before and after CEA by subjective improvement and objective visual assessment using CSV-1000, an instrument used to test contrast sensitivity. RESULTS: OBF increased after CEA on the operated side (mean MBR 33.5 vs 38.2, p < 0.001) but not on the non-operated side (mean MBR 37.8 vs 37.5, p = 0.50). After CEA, 23 patients (56.1%) reported subjective visual improvement on the operated side. The mean CSV-1000 score among the patients with increased OBF after CEA (5.44 vs 5.88, p = 0.04) but not among those without increased OBF (5.48 vs 5.95, p = 0.09). The mean CSV-1000 scores increased significantly after CEA in 18 patients with decreased vision and decreased OBF (4.51 vs 5.37, p < 0.001), but not in the 23 patients without those (6.19 vs 6.31, p = 0.6). CONCLUSION: CEA may successfully reverse visual dysfunction caused by chronic ocular ischemia due to carotid artery stenosis by increasing OBF.

Ocular blood flow by laser speckle flowgraphy to detect cerebral ischemia during carotid endarterectomy.

Laser speckle flowgraphy (LSFG) is a noninvasive technique that can measure relative blood flow velocity in the optic fundus contributed by the ophthalmic artery, the main first branch originating from the internal carotid artery (ICA). The aim of this study was to assess the feasibility of ocular blood flow measurement by LSFG to detect ischemic stress due to carotid clamping during carotid endarterectomy (CEA). Nineteen patients undergoing CEA with ocular blood flow measurement by LSFG and intraoperative monitoring (IOM) were prospectively enrolled between August 2016 and March 2019. The mean blur rate (MBR) of ocular blood flow by LSFG, representing relative blood flow of the branch of the retinal artery originating from the optic nerve head, was compared between before and after carotid clamping during CEA. The correlation between the reduction ratio of MBR and the regional saturation oxygen (rSO2) index by near infrared spectroscopy was investigated. Ocular blood flow measurement by LSFG could not be performed in one patient with a severe cataract. In the other 18 patients, LSFG could be performed in all 106 sessions during surgery. The MBR reduction ratio between before and after carotid clamping ranged from - 12 to 100%. The MBR reduction ratio was positively correlated with the rSO2 index (r = 0.694, 95% confidence interval: 0.336-0.877, p = 0.001). The MBR reduction ratio of ocular blood flow by LSFG after carotid clamping was significantly correlated with the rSO2 index. The ocular blood flow by LSFG could be considered an adjunct modality for evaluating cerebral ischemic tolerance during CEA.

Does hemispheric vascular regulation differ significantly in glaucoma patients with altitudinal visual field asymmetry? A single-center, prospective study.

PURPOSE: Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. METHODS: 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 profound hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. RESULTS: Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p < 0.04 and p < 0.02 respectively) in-between the hemispheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. CONCLUSION: Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetric altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.

Diagnostic performance of laser speckle flowgraphy in glaucoma: a systematic review and meta-analysis.

PURPOSE: To evaluate the diagnostic value of laser speckle flowgraphy (LSFG) in glaucoma by investigating the mean blur rate (MBR) in the optic nerve head. METHODS: Systematic literature search was performed in the CENTRAL, Web of Science, PubMed, and EMBASE databases to obtain relevant studies published until December 2020 without restrictions. The Newcastle-Ottawa Scale (NOS) was used for study quality assessment. The outcome measures included the MBRs of the entire (MA), vascular (MV), and tissue (MT) areas. Subgroup analyses were performed according to glaucoma type. All data were analyzed using RevMan and Comprehensive Meta-Analysis 3.3 software. RESULTS: Fifteen studies, including 692 glaucomatous and 386 healthy eyes, were included. Of these, 11 studies reported the MA, MV, and MT, three studies only reported MT, and one study only reported MV. All were classified as case-control studies and had good NOS scores. The meta-analysis showed that the MA and MT were significantly reduced in glaucomatous eyes (mean difference [MD] - 5.59, 95% confidence interval [CI] - 6.19 to - 4.99, p = 0.1; MD - 2.2, 95% CI - 2.49 to - 1.91, p = 0.07, respectively) with moderate heterogeneity (p = 0.1, I2 = 38%; p = 0.07, I2 = 39%, respectively). There was also a significant difference in the MV between glaucomatous and healthy eyes (MD - 5.92, 95% CI - 7.77 to - 4.07) with significant heterogeneity (p = 0.0003, I2 = 69%). The subgroup analyses revealed significant differences in the MBR among different glaucoma types. CONCLUSIONS: Glaucoma is closely related to ocular blood flow changes. This meta-analysis suggests that LSFG is a feasible diagnostic tool for glaucoma. However, further longitudinal prospective studies are needed.

Hemodynamics of the temporal and nasal short posterior ciliary arteries in pseudoexfoliation syndrome.

PURPOSE: The aim of this study was to investigate blood flow changes in the temporal and nasal short posterior ciliary arteries (SPCAs) in pseudoexfoliation syndrome using color Doppler ultrasonography. METHODS: This prospective clinical study included 67 eyes of 53 patients scheduled for cataract surgery. Pseudophakic eyes, eyes with traumatic cataract, were excluded. The demographic characteristic of the patients were recorded. Ocular blood flow was measured using 6-10 MHz Doppler ultrasound. Peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (Vm), and resistive index (RI) in the temporal and nasal SPCAs were determined for 39 eyes of 30 patients with pseudoexfoliation syndrome and cataract and a control group comprising 28 eyes of 23 patients with senile cataract. RESULTS: Compared to the control group, patients with pseudoexfoliation syndrome had significantly lower PSV (8.85 ± 2.88 cm/s), EDV (3.21 ± 1.12 cm/s), and Vm (5.27 ± 1.98 cm/s) in the temporal SPCA (PSV P = .001; EDV P = .002; Vm P = .001). There was no difference in velocities in the nasal SPCA. RI of both the temporal and nasal SPCA did not differ statistically between the groups (temporal SPCA P = .517, nasal SPCA P = .752) CONCLUSION: There were significant decreases in temporal SPCA hemodynamic parameters in patients with pseudoexfoliation syndrome. These findings suggest that temporal SPCA ocular blood flow measurements have greater diagnostic value than those of the nasal SPCA.

Ocular microcirculation changes, measured with laser speckle flowgraphy and optical coherence tomography angiography, in branch retinal vein occlusion with macular edema treated by ranibizumab.

PURPOSE: This study searched for early predictive vascular biomarkers for visual outcomes in eyes with macular edema caused by branch retinal vein occlusion (BRVOME). METHODS: Twenty-four eyes of 24 subjects with BRVOME were treated with the intravitreal injection of ranibizumab (IVR) for at least 6 months. We measured mean blur rate (MBR) in the optic nerve head (ONH) and vessel density (VD) in the macula with laser speckle flowgraphy and optical coherence tomography angiography, respectively. RESULTS: Six-month post-IVR best-corrected visual acuity (BCVA) was correlated positively with age, pre-IVR BCVA, 1-month post-IVR BCVA, 3-month post-IVR BCVA and pre-IVR systolic blood pressure (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.02, respectively) and negatively with pre-IVR overall MBR, 1-month post-IVR overall MBR, 6-month post-IVR overall MBR, 3-month post-IVR deep retinal capillary plexus (DCP) VD and 6-month post-IVR DCP VD (P = 0.03, P = 0.03, P = 0.02, P = 0.01 and P = 0.005, respectively). Furthermore, a multiple regression analysis showed that pre-IVR overall MBR (ß = - 0.67, P = 0.009) was among independent prognostic factors predicting 6-month post-IVR BCVA. Six-month post-IVR DCP VD was also correlated with overall MBR at all time points. CONCLUSION: ONH blood flow may be a pre-IVR biomarker of both visual outcomes and post-IVR deep macular microcirculation in eyes with BRVOME.

Effects of testosterone on intraocular pressure, thicknesses of retinal nerve fiber layer, ganglion cell complex, macula and on ocular blood flow in female-to-male transgender persons.

PURPOSE: To compare the effects of testosterone on intraocular pressure (IOP), thicknesses of retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), macula and on ocular blood flow between female-to-male transgender (FMT) persons who use testosterone and healthy women and healthy men. METHOD: The study included 39 eyes of 20 FMT(Group 1), 40 eyes of 20 healthy women (Group 2), and 42 eyes of 21 healthy men (Group 3). In all subjects, RNFL, GCC and, macular thicknesses (MT) were measured by optical coherence tomography (OCT). Ocular blood flow was measured by Color Doppler Ultrasonography in all subjects. RESULTS: IOP levels in FMT were significantly higher than men (p = 0.025). Superior (Sup), inferior (Inf) thicknesses of parafovea, and nasal thickness of perifovea in FMT were significantly higher than the Group 2 (p = 0.024, p = 0.037, p = 0.018). Sup thickness of perifovea in FMT was significantly higher than Group 3 (p = 0.011). Inf thickness of perifovea in FMT was significantly higher than Group 2 and 3 (p = 0.038, p = 0.002). Mean thickness of RNFL Inf in FMT was significantly higher than the Group 2 and 3 (p = 0.039, p = 0.032). Avg and Inf thicknesses of GCC in FMT were significantly higher than group 2 (p = 0.02, p = 0.005). In correlation test, systole/diastole ratio(S/D) in ophthalmic artery (OA) (r = 0.504, p = 0.028) and Inf thickness of perifovea (r = 0.485, p = 0.035) were positively correlated with the serum levels of testosterone in FMT. CONCLUSIONS: We found that the use of supraphysiologic testosterone dose increased IOP and the thicknesses of macula, RNFL, and GCC in FMT. Serum testosterone level was positively correlated with S/D ratio in the OA.