Fundus Blood Flow Research Articles

The Retinal Blood Flow Density Is Related to the Pathological Severity of Diabetic Kidney Disease

Introduction: This study aimed to investigate the correlation between fundus blood flow parameters and the severity of pathological biopsy in patients with diabetic kidney disease (DKD). Methods: Data of patients with type 2 diabetes mellitus who completed renal pathology biopsies and optical coherence tomography angiography (OCTA) examinations, including renal function, 24-h urine protein quantification, and macular flow imaging, were collected. DKD pathology biopsies were graded as stages 1–4, and differences and correlations of the parameters were compared between groups. The grading was transformed into early (stage 1) and late (stages 2–4), and regression analyses were conducted to develop a model, draw a nomogram, and test efficacy. Results: This study included 157 eyes from 157 individuals in total. Urinary microalbumin and to urinary creatinine ratio (mALB/NCR) increased with pathological grading, whereas while glomerular filtration rate was decreased (p < 0.01). Corresponding retinal blood flow in superficial, deep, and full paracentral rings was decreased, which correlated with pathological grading (p < 0.01), with the highest blood flow density in the whole layer (r2 = −0.707). Meaningfully, in the early DKD model (area under the curve = 0.929 [0.889–0.970], p < 0.01), whole-layer blood flow density, mALB/NCR, and diabetes duration were statistically significant. Conclusions: The decrease in macular retinal blood flow density detected by OCTA is closely associated with the increase in pathological grading of DKD and can be used as a noninvasive parameter for monitoring early changes in DKD.

Short-term effects of sunlight exposure on fundus blood flow perfusion in children: a randomised controlled trial

AimTo evaluate the short-term effects of different sunlight exposure on fundus blood flow perfusion (BFP) after near work.MethodsIn this parallel randomised controlled trial, 81 students aged 7–15 with spherical equivalent...

Retinal thickness and fundus blood flow density changes in chest pain subjects with dyslipidemia.

To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography (OCTA). All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination. According to the serum lipid levels, the participants were divided into the control group and the dyslipidemia group. The retina thickness and fundus blood flow density were determined using OCTA. The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age- and sex-matched participants without dyslipidemia. The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior (P=0.004 and P=0.014, respectively) and temporal (P=0.015 and P=0.019, respectively) regions, both inner and outer layers. In terms of blood flow density in the macula or optic disk, there was a decreasing trend in the dyslipidemia group compared with the control group, especially in the inferior and temporal regions. Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density. Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.

Retinal and choroidal microvascular characterization and density changes in different stages of diabetic retinopathy eyes.

The purpose of this study was to evaluate the changes in fundus vascular density and micromorphological structure of all vascular plexuses during the different stages of diabetic retinopathy (DR), and the correlation between fundus blood flow and the DR severity. This observational cross-sectional study was conducted of 50 eyes with different stages of DR, 25 diabetes mellitus (DM) patients without clinical signs of DR and 41 healthy eyes. The foveal avascular zone (FAZ), vessel density of superficial capillary plexus (SCP), and deep retinal capillary plexus (DCP) were acquired by RTVue XR Avanti OCTA device. The perfusion density (PD), skeleton vessel density (SVD) was manually calculated using ImageJ. The area under receiver operating characteristic (ROC) curve was used to determine the diagnostic value of OCTA parameters in distinguishing DR and healthy eyes. The choroidal VD were significantly higher in the healthy group than in the DM without DR, NPDR, and PDR groups (p < 0.001). The mean retinal parafovea VD, PD, and retinal SVD were higher in healthy and DM without DR eyes compared with NPDR and DR eyes in all vascular layers (p < 0.001). The parafoveal VD of SCP, and DCP decreased, and FAZ area increased with the exacerbation of DR. The OCTA parameters, including FAZ area, parafovea VD, PD, and SVD in all vascular layers showed significant correlation with DR severity (all p < 0.001). ROC curves of OCTA parameters (FAZ area, retinal parafovea VD, retinal PD, and SVD in all vascular layers) for had high sensitivity and specificity in distinguishing DR versus healthy eyes. The choroidal parafovea VD, retinal parafovea VD, retinal PD, and SVD in the two plexuses decreased, and retinal FAZ area increased significantly with worsening DR. VD, PD, and SVD might be potential early biomarkers indicating the progression of DR before appearance of clinically PDR in patients with DM. In this study, OCTA parameters had high sensitivity and specificity in distinguishing DR and healthy eyes.

Novel superpixel method to visualize fundus blood flow resistivity in healthy adults

We aimed to perform superpixel segmentation of ocular blood flow maps obtained using laser speckle flowgraphy (LSFG) and investigate the effects of systemic parameters such as body weight, height, and sex on ocular blood flow resistivity. We studied 757 healthy participants (583 men, 174 women). We calculated the average beat strength over mean blur rate (BOM) as a LSFG resistivity index, as a function of age and sex using ordinary regions of interest (ROI) centered on the optic nerve head (ONH), the retinal vessels region and tissue around the ONH, and the choroid (CHD). We compared the ROI and superpixel-based methods, which are segmented based on image processing, for calculating the BOM. The sex differences in the BOM for the ONH, retinal-vessels region and tissue region of the ONH and CHD were significant for individuals aged ≤ 50 years (P < 0.01) but not those > 50 years old (P > 0.05). The average BOMs calculated using the ROI and superpixel methods were strongly correlated in the ONH (coefficient = 0.87, R2 = 0.8, P < 0.0001, n = 5465). In summary, a superpixel-segmented BOM map is suitable for two-dimensional visualization of ocular blood flow resistivity.

Retracted: Evaluation of Fundus Blood Flow Perfusion in Patients with Diabetic Retinopathy after PPV with Fundus Color Doppler Based on Big Data Mining.

[This retracts the article DOI: 10.1155/2022/7414165.].

Evaluation of Fundus Blood Flow Perfusion in Patients with Diabetic Retinopathy after PPV with Fundus Color Doppler Based on Big Data Mining.

In this paper, we have carefully investigated the clinical phenotype and genotype of patients with Johanson-Blizzard syndrome (JBS) with diabetes mellitus as the main manifestation. Retinal vessel segmentation is an important tool for the detection of many eye diseases and plays an important role in the automated screening system for retinal diseases. A segmentation algorithm based on a multiscale attentional resolution network is proposed to address the problem of insufficient segmentation of small vessels and pathological missegmentation in existing methods. The network is based on the encoder-decoder architecture, and the attention residual block is introduced in the submodule to enhance the feature propagation ability and reduce the impact of uneven illumination and low contrast on the model. The jump connection is added between the encoder and decoder, and the traditional pooling layer is removed to retain sufficient vascular detail information. Two multiscale feature fusion methods, parallel multibranch structure, and spatial pyramid pooling are used to achieve feature extraction under different sensory fields. We collected the clinical data, laboratory tests, and imaging examinations of JBS patients, extracted the genomic DNA of relevant family members, and validated them by whole-exome sequencing and Sanger sequencing. The patient had diabetes mellitus as the main manifestation, with widened eye spacing, low flat nasal root, hypoplastic nasal wing, and low hairline deformities. Genetic testing confirmed the presence of a c.4463 T > C (p.Ile1488Thr) pure missense mutation in the UBR1 gene, which was a novel mutation locus, and pathogenicity analysis indicated that the locus was pathogenic. This patient carries a new UBR1 gene c.4463 T > C pure mutation, which improves the clinical understanding of the clinical phenotypic spectrum of JBS and broadens the genetic spectrum of the UBR1 gene. The experimental results showed that the method achieved 83.26% and 82.56% F1 values on CHASEDB1 and STARE standard sets, respectively, and 83.51% and 81.20% sensitivity, respectively, and its performance was better than the current mainstream methods.

Extreme Hyperglycemia Causes Vascular Hypoperfusion at Optic Nerve Head in Diabetic Patients (DM)

Background: OCT angiography (OCTA) and laser speckle flowgraphy (LSFG) are novel and noninvasive imaging modalities which could evaluate fundus blood flow quantitatively. However, the role of OCTA and LSFG as diagnostic tools has not been widely investigated. Previous reports indicated that NO, reduced by hyperglycemia, exerts a key role for the autoregulation of retinal blood flow. We designed this study to evaluate the retinal blood flow by OCTA and LSFG in hyperglycemic DM. Method: 10 patients with extreme hyperglycemia at our outpatient clinic (FPG&amp;gt;250mg/dL, or casual PG&amp;gt;350mg/dL, age 58±5, 7 males, HbA1c 11.1±0.5%) and 32 healthy volunteers (age 48±2, 17 males) were included. Vascular density was calculated using OCTA. LSFG measured relative blood velocity (mean blur rate: MBR) in the optic nerve head (ONH). MBR-A (the mean of all area), MBR-V (the vessel mean) and MBR-T (the tissue mean) were analyzed. Result: OCTA revealed no difference between two groups in the vascular density at macula (47.37±1.14% for DM and 47.44±0.67% for NDM) and a tendency of decrease in the diabetic vascular density at ONH (40.14±3.56% for DM and 42.48±1.25% for NDM) without statistical significance. With LSFG, MBR-A and MBR-T did not exhibit significant differences, while MBR-V significantly decreased in DM compared to the healthy (42.85±2.05% for DM, 49.25±1.34% for NDM, p = 0.025). Discussion: Our results demonstrated that vascular hypoperfusion at ONH was associated with extreme hyperglycemia in DM with tendency to decrease in vascular density. It is generally supposed that the retinal blood flow decreases in DM and acute hyperglycemia. In DM actually presented physiological changes in the retina. Besides, there is a report that autoregulation of blood flow in the ONH is disrupted in diabetic rabbits, as well as in healthy ones with uncoupled gap junctions. It is possible that the similar mechanisms are involved in ONH blood flow decrease observed in this study. Disclosure T. Mitsumatsu: None. F. Yagi: None. Y. Kondo: None. A. Anraku: None. S. Okahata: None. K. Sakamoto: None. G. Tomita: None. T. Shiba: Speaker's Bureau; Self; Shionogi &amp; Co., Ltd., Pfizer Inc., Merck Sharp &amp; Dohme Corp., Kowa Company, Ltd., Daiichi Sankyo Company, Limited.

Evaluation of Fundus Blood Flow in Normal Individuals and Patients with Internal Carotid Artery Obstruction Using Laser Speckle Flowgraphy.

PurposeWe investigated whether laser speckle flowgraphy (LSFG) results are comparable in both eyes and whether it is useful in the diagnosis of disparity in ocular ischemic syndrome (OIS) patients.MethodsWe compared the mean blur rate (MBR) value for various fundus regions in both eyes of 41 healthy subjects and 15 internal carotid artery occlusion (ICAO) cases. We calculated the standard value of the Laterality Index (LI), which was the MBR comparison of both eyes in each of the regions, in the control subjects. We then investigated the correlation between both eyes for the LIs in the entire fundus, the degree of ICAO and visual function.ResultsThe disparity of the LIs in both eyes was least in the entire area of the fundus in control subjects and there was a significant correlation between both eyes of the 41 healthy individuals (P = 0.019). Significant correlations were found for the LI, visual acuity and degree of ICAO. The specificity and sensitivity of LI in the entire area was 93.8% and 100%, respectively.ConclusionsLSFG revealed normal individuals have symmetrical fundus blood flow. LSFG could detect OIS and might be a useful tool for detecting disparities in fundus blood flow.

L-Citrulline dilates rat retinal arterioles via nitric oxide- and prostaglandin-dependent pathways in vivo

l-Citrulline is an effective precursor of l-arginine produced by the l-citrulline/l-arginine cycle, and it exerts beneficial effects on the cardiovascular system by supporting enhanced nitric oxide (NO) production. NO dilates retinal blood vessels via the cyclooxygenase-mediated pathway. The purpose of this study was to examine the effects of l-citrulline on retinal circulation and to investigate the potential involvement of NO and prostaglandins in l-citrulline-induced responses in rats. l-Citrulline (10–300 μg kg−1 min−1, i.v.) increased the diameter of retinal arterioles without significantly changing mean blood pressure, heart rate, and fundus blood flow. The vasodilator response of retinal arterioles to l-citrulline was significantly diminished following treatment with NG-nitro-l-arginine methyl ester (30 mg/kg, i.v.), an NO synthase inhibitor, or indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor. In addition, α-methyl-dl-aspartic acid (147 mg/kg, i.v.), an inhibitor of argininosuccinate synthase, the rate-limiting enzyme for the recycling of l-citrulline to l-arginine, diminished the l-citrulline-induced retinal vasodilation. These results suggest that both NO- and prostaglandin-dependent pathways contribute to the l-citrulline-induced vasodilation of rat retinal arterioles. The l-citrulline/l-arginine recycling pathway may have more importance in regulating vascular tone in retinal blood vessels than in peripheral resistance vessels.

Bilateral Common Carotid Artery Occlusion in the Rat as a Model of Retinal Ischaemia

Ocular ischaemic syndrome is a devastating eye disease caused by severe carotid artery stenosis. The purpose of the study was to develop a reliable rat model for this syndrome by means of common carotid artery occlusion and a controllable needle suture method. Adult Wistar rats were subjected to common carotid artery occlusion and sham surgery. The common carotid artery was ligated unilaterally or bilaterally with needles of different diameters, and ocular arterial filling time was examined by fluorescein fundus angiography at different time points. Haematoxylin-eosin staining of vessels and degree of stenosis were considered outcome measures. The ocular blood flow was monitored and measured by laser doppler flowmetry. Needles with a diameter of 0.4 mm were more effective in developing severe stenosis of the common carotid arteries compared with needles of other diameters. Bilateral common carotid artery occlusion was a more effective model than unilateral occlusion. The arterial filling time was significantly increased at 14 and 21 days after ligation (5.75 ± 0.45 and 6.27 ± 0.95 s, respectively) compared with arterial filling time before surgery (5.22 ± 0.64 s). The total blood flow in the sham surgery group was significantly higher than in the bilateral common carotid artery occlusion group. The fundus blood flow was statistically different between the two groups, whereas that of the anterior segment was not. In conclusion, the authors have established a rat model of ocular ischaemic syndrome via a controllable needle suture method, which was reliable up to 2–3 weeks after surgery.

Intravenously administered phosphodiesterase 4 inhibitors dilate retinal blood vessels in rats

In the present study, we examined effects of intravenously administered inhibitors of phosphodiesterase 4 (rolipram and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro-20-1724)) and non-selective inhibitor of phosphodiesterases (theophylline) on diameter of retinal blood vessel and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 μg/kg, i.v.) to eliminate any nerve activity and prevent the eye movement under artificial ventilation. Methoxamine was used to maintain adequate systemic circulation. Ocular fundus images were captured with an original high-resolution digital fundus camera for small animals. Diameters of retinal blood vessels contained in the digital images were measured using image-processing softwares on a personal computer. Fundus blood flow was measured using a laser Doppler flow meter. Both rolipram (0.01–10 μg/kg/min, i.v.) and Ro-20-1724 (0.01–10 μg/kg/min, i.v.) increased diameters of retinal blood vessels in a dose-dependent manner without significant effect on systemic blood pressure, heart rate and fundus blood flow. The effects of phosphodiesterase 4 inhibitors on retinal arterioles were greater than those on retinal venules. Similarly, theophylline (0.1–10 mg/kg/min, i.v.) dilated retinal blood vessels, whereas it decreased blood pressure and increased heart rate markedly. These results suggest that phosphodiesterase 4 contributes to maintenance of retinal vascular tone. Inhibitors of phosphodiesterase 4 could be considered as a candidate for therapeutic drugs to treat diseases associated with disorders of retinal circulation without severe cardiovascular side-effects.

Stimulation of prostanoid IP and EP 2 receptors dilates retinal arterioles and increases retinal and choroidal blood flow in rats

We examined the effects of vasodilatory prostaglandins (prostacyclin and prostaglandin E 2) and selective agonists for prostanoid EP 2 and EP 4 receptor on the diameters of retinal blood vessels and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 μg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye and infused with a mixture solution of norepinephrine and epinephrine (1:9) to maintain adequate systemic circulation under artificial ventilation. Fundus images were captured with a digital camera that was equipped with the special objective lens for small animals, and the diameters of retinal arterioles and venules were measured on a personal computer. Fundus blood flow was estimated using a laser Doppler flowmetry. Intravenous infusions of prostacyclin and prostaglandin E 2 dilated retinal blood vessels, increased fundus blood flow and decreased systemic blood pressure in a dose-dependent manner. The effects of vasodilatory prostaglandins on retinal arterioles were greater than those on retinal venules. Similarly, a prostanoid EP 2 receptor agonist (ONO-AE1-259-01) dilated retinal blood vessels, and increased fundus blood flow and decreased systemic blood pressure. However, a prostanoid EP 4 receptor agonist (ONO-AE1-329) failed to increase fundus blood flow, despite its comparable depressor response with those to vasodilatory prostaglandins and the prostanoid EP 2 receptor agonist. The responses to forskolin, an activator of adenylyl cyclase, were very similar to those to prostacyclin and the prostanoid EP 2 receptor agonist. These results suggest that prostacyclin and prostaglandin E 2 act as vasodilators in retinal and choroidal circulation, and prostanoid IP and EP 2 receptors play an important role in the regulation of ocular hemodynamics in rats.

Intravenously Administered Vasodilatory Prostaglandins Increase Retinal and Choroidal Blood Flow in Rats

We established an experimental system for measuring blood flow in the rat fundus and examined whether intravenously administered vasodilatory prostaglandins (PGE1, PGE2, and PGI2), 8-(4-chlorophenylthio)-cAMP (a cAMP analogue), and nicardipine (a Ca2+-channel blocker) increase fundus blood flow (FBF). Under artificial ventilation, rats were injected with tetrodotoxin (50 µg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye. After tetrodotoxin, the rats were infused with norepinephrine (0.3 – 0.5 µg ⋅ kg−1 ⋅ min−1) and epinephrine (2.7 – 4.5 µg ⋅ kg−1 ⋅ min−1) simultaneously to maintain adequate systemic circulation. We found that intravenous infusion of PGE1 (2 – 10 µg ⋅ kg−1 ⋅ min−1), PGE2 (3 – 30 µg ⋅ kg.1. min−1), and PGI2 (1 – 10 µg ⋅ kg−1 ⋅min−1) increased the FBF in a dose-dependent manner. The vasodilatory PGs decreased arterial pressure, whereas they did not affect heart rate. Like vasodilatory PGs, 8-(4-chlorophenylthio)-cAMP (30 µmol/kg, i.v.) increased FBF and decreased arterial pressure. While infusion of nicardipine (0.3 – 3 µg ⋅ kg−1 ⋅min−1) produced comparable depressor responses with those to vasodilatory PGs and the cAMP analogue, it did not increase FBF. These results suggest that vasodilatory PGs and cAMP act more selectively than Ca2+- channel blockers on retinal /choroidal blood vessels. Therefore, the vasodilatory PGs might be considered to be possible candidates for the therapeutics to treat disorders of retinal /choroidal circulation.

Utilization of the Delay Phenomenon Improves Blood Flow and Reduces Collagen Deposition in Esophagogastric Anastomoses

Complications of anastomotic healing are a common source of morbidity and mortality after esophagogastrostomy. The delay phenomenon is seen when a skin flap is partially devascularized in a staged procedure prior to its definitive placement, resulting in increased blood flow at the time of grafting. This effect may be applied to esophagogastrectomy, potentially reducing anastomotic complications. The purpose of this investigation was to apply the delay principle to the gastrointestinal tract, investigate mechanisms by which it occurs and examine the effects of delay on anastomotic healing. Thirty-seven opossums were assigned to Sham (n = 5), Immediate (n = 14), and Delay (n = 18) groups. Each underwent laparotomy and measurement of baseline gastric fundus blood flow. The Delay and Immediate animals underwent ligation of the left, right, and short gastric vessels and subsequent measurement of gastric fundus blood flow. The Delay group underwent repeat measurement of blood flow, esophagogastrectomy, gastric tubularization, and esophagogastrostomy 28 days after vessel ligation. The Immediate group completed the procedure immediately after vessel ligation. The anastomoses in both groups were harvested 32 days after esophagogastrostomy. The Sham group underwent blood flow measurement on initial laparotomy, followed by harvesting of esophagogastric junction 60 days later. Sections taken through the anastomoses were examined with trichrome-staining and immunohistochemistry (IHC) for actin. Collagen content of the gastric submucosa 5 mm below the anastomosis was quantified, and preservation of the muscularis propria and muscularis mucosa was determined histologically. Capillary content of the esophagogastric junction was quantified using IHC for vascular endothelium in the Delay and Sham groups. Blood flow decreased by 73% following vessel ligation in Delay and Immediate groups. The Delay group had over 3 times the gastric blood flow of the Immediate group at the time of anastomosis at 16 (interquartile range [IQR] 11-17) versus 5, (IQR 5-6) mL/min/100 g (P = 0.000003). Two Immediate animals developed anastomotic leak and died; the Delay group had no complications. Submucosal collagen content in Sham, Delay, and Immediate groups were 57% (IQR 52-62), 65% (IQR 57-72), and 71% (IQR 60-82), respectively (P = 0.0004). The median distance of full-thickness atrophy of the muscularis propria was 0.10 mm (IQR 0-0.60 mm) in the Delay group and 0.53 mm (IQR 0.03-0.80 mm) in the Immediate group (P = 0.346). Five percent of the Delay group had atrophy of the muscularis mucosa, whereas 19% of Immediate animals had atrophy of this layer (P = 0.023). Compared with the Sham group, all Delay animals developed dilation of the right gastroepiploic artery and vein. A median of 27 (IQR 23-33) capillaries per 20x field was observed in the Sham fundus and 38 (IQR 31-46) in the Delay fundus (P = 0.037). The delay effect is associated with both vasodilation and angiogenesis and results in increased blood flow to the gastric fundus prior to esophagogastric anastomosis. Animals undergoing delayed operations have less anastomotic collagen deposition and ischemic injury than those undergoing immediate resection. Clinical application of the delay effect in patients undergoing esophagogastrectomy may lead to a decreased incidence of leak and stricture formation.

Canine gastric mucosal vasodilation with prostaglandins and histamine analogs.

The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.