Microvasculature In Patients Research Articles

Retinochoroidal vascular plexuses in patients with iron deficiency anaemia

ABSTRACT Clinical relevance Optical coherence tomography angiography (OCT-A) may enable the identification of alteration in the retinochoroidal microvasculature in patients with iron deficiency anaemia. Background To investigate the presence of macular microvascular alterations in females with IDA by using OCT-A. Methods This is a cross-sectional comparative study. Forty patients with IDA and 35 age-matched healthy women underwent a complete ophthalmologic examination and OCT-A imaging. Foveal avascular zone parameters and the vessel density in the superficial (SCP) and deep capillary plexus (DCP) were calculated using automated software. All measurements were compared between groups. Correlations between the OCT-A metrics and haematological laboratory parameters were evaluated. Results Compared to healthy subjects, IDA patients revealed significantly decreased vessel density of the SCP in all parafoveal quadrants (p < 0.05). In contrast, vessel density analysis in DCP has shown no statistically significant difference in all parafoveal quadrants (p > 0.05). Although foveal vessel density in both SCP and DCP were higher in the IDA group, only the foveal vessel density in DCP was significantly higher than controls (p = 0.001). The mean values of the foveal avascular zone area and perimeter and choriocapillaris flow area were significantly lower in the IDA group (p < 0.05). The parafoveal vessel density in SCP, foveal avascular zone area, and choriocapillaris flow area were positively correlated with haematological parameters including haemoglobin, haematocrit, mean corpuscular haemoglobin, and mean corpuscular volume (p < 0.01). Conclusion Patients with IDA had decreased parafoveal vessel density in the SCP, but not the DCP. Foveal avascular zone metrics and choriocapillaris flow area measurements were significantly lower in IDA.

Evaluation of the direct effects on retinal and choroidal microvascularity of systemic scleroderma

ObjectiveOcular involvement in systemic sclerosis (SSc) has been documented; however it cannot be distinguished from secondary changes due to concomitant hypertension.Therefore, the aim of this prospective cross-sectional study was to demonstrate the direct effects of Ssc on retinal and choroidal microvasculature in patients without hypertension. Methods47 SSc patients and 44 age- and sex-matched healthy control subjects were enrolled in this study. In fundus examination: Increased vascular tortitis, focal or general arteriolar narrowing, arteriovenous notch, severe exudation, microhemorrhage, and pigment epithelial changes in the retina of SSc patients without hypertension were investigated. Patients with at least two of the above findings were considered to have retinopathy After that, patients were divided into two groups according to the presence of retinopathy in this study. Retinal and choroidal microvasculature were evaluated using optical coherence tomography angiography. ResultsThere was a significant decrease in SSc patients with retinopathy in both superficial capillary plexus vessel density (SCP VD) and deep capillary plexus vessel density (DCP VD) compared to the control group. Full avascular zone (FAZ) evaluation tool variables (FAZ area, FAZ perimeter, foveal density) were significantly lower in all Ssc patients than in the healthy control group. It was found that the flow in the 1 mm and 3 mm circular area (Outer Retina 1–3 mm Flow Area) increased significantly in Ssc patients with retinopathy. Choroidal flow (Choriocapillaries 1 mm Flow Area) was statistically lower in Ssc patients with retinopathy. ConclusionsWe have showed an increase in the outer retina 1–3 mm flow area (circular area of the outer retina fold covering the fovea) despite the decrease in vascular density and choroidal thickness in scleroderma patients with retinopathy. Hence, we first demonstrated that Ssc itself may have an effect on retinal and choroidal microvasculature, independent of hypertension.

Standard exercise stress testing attenuates peripheral microvascular function in patients with suspected coronary microvascular dysfunction

BackgroundThe effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD.MethodsIn a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia.ResultsLnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62–0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40–0.81; P = 0.34).ConclusionsCMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.

Peripapillary Retinal Nerve Fiber Layer and Microvasculature in Prolonged Type 2 Diabetes Patients Without Clinical Diabetic Retinopathy.

PurposeThe purpose of this study to identify the effects of prolonged type 2 diabetes (T2DM) on the peripapillary retinal nerve fiber layer (pRNFL) and peripapillary microvasculature in patients with prolonged T2DM without clinical diabetic retinopathy (DR).MethodsSubjects were divided into 3 groups: controls (control group; 153 eyes), patients with T2DM < 10 years (DM group 1; 136 eyes), and patients with T2DM ≥ 10 years (DM group 2; 74 eyes). The pRNFL thickness and peripapillary superficial vessel density (VD) were compared. Linear regression analyses were performed to identify factors associated with peripapillary VD in patients with T2DM.ResultsThe mean pRNFL thicknesses of the control group, DM group 1, and DM group 2 were 96.0 ± 7.9, 94.5 ± 0.9, and 92.2 ± 8.2 µm, respectively (P < 0.001). The VDs were 18.24 ± 0.62, 17.60 ± 1.47, and 17.15 ± 1.38 mm−1 in the control group, DM group 1, and DM group 2, respectively (P < 0.001). In multivariate linear regression analyses, visual acuity (B = −2.460, P = 0.001), axial length (B = −0.169, P = 0.008), T2DM duration (B = −0.056, P < 0.001), and pRNFL (B = 0.024, P = 0.001) were significant factors affecting the peripapillary VD in patients with T2DM.ConclusionsPatients with T2DM without clinical DR showed thinner pRNFL and lower peripapillary VD and perfusion density (PD) compared with normal controls, and such damage was more severe in patients with T2DM ≥ 10 years. Additionally, peripapillary VD was significantly associated with best-corrected visual acuity (BCVA), axial length, T2DM duration, and pRNFL thickness in patients with T2DM.

Optical Coherence Tomography Angiography Reveals Distinct Retinal Structural and Microvascular Abnormalities in Cerebrovascular Disease.

Cerebrovascular disease (CeVD) is one of the leading global causes of death and severe disability. To date, retinal microangiopathy has become a reflection of cerebral microangiopathy, mirroring the vascular pathological modifications in vivo. To evaluate the retinal structure and microvasculature in patients with CeVD, we conducted a cross-sectional study in Zhongshan Ophthalmic Center and Department of Neurology of Third Affiliated Hospital, Sun Yat-sen University using optical coherence tomography angiography (OCTA). CeVD patients (n = 121; 238 eyes) and healthy controls (n = 44; 57 eyes) were included in the analysis. The CeVD group showed significant thinning of the peripapillary retinal nerve fiber layer (pRNFL) thickness in the temporal and nasal quadrants, and thinning of the macular ganglion cell-inner plexiform layer (GC-IPL) in the inferior quadrant, while macular microvasculature reduction was prominent in all nine quadrants. There were significant correlations between OCTA parameters, visual acuity, and transcranial doppler parameters in the CeVD group. The specific structural parameters combining microvasculature indices showed the best diagnostic accuracies (AUC = 0.918) to discriminate CeVD group from healthy controls. To conclude, we proved that OCTA reveals specific patterns of retinal structural changes and extensive macular microvascular changes in CeVD. Additionally, these retinal abnormalities could prove useful disease biomarkers in the management of individuals at high risk of debilitating complications from a cerebrovascular event.

Impact of blood pressure control on retinal microvasculature in patients with chronic kidney disease

Chronic kidney disease (CKD) is an emerging disease worldwide. We investigated the relationship between blood pressure (BP) control and parafoveal retinal microvascular changes in patients with CKD. This case–control study enrolled 256 patients with CKD (stage 3–5) and 70 age‐matched healthy controls. Optical coherence tomography angiography showed lower superficial vascular plexus (SVP) vessel density, lower deep vascular plexus (DVP) vessel density, and larger SVP flow void area in the CKD group. The BP parameters at enrollment and during the year before enrollment were collected in patients with CKD. Partial correlation was used to determine the relationship between BP parameters and microvascular parameters after controlling for age, sex, diabetes mellitus, axial length, and intraocular pressure. The maximum systolic blood pressure (SBP) (p = 0.003) and within-patient standard deviation (SD) of SBP (p = 0.006) in 1 year were negatively correlated with SVP vessel density. The average SBP (p = 0.040), maximum SBP (p = 0.001), within-patient SD of SBP (p < 0.001) and proportion of high BP measurement (p = 0.011) in 1 year were positively correlated with the SVP flow void area. We concluded that long-term SBP was correlated with SVP microvascular injury in patients with CKD. Superficial retinal microvascular changes may be a potential biomarker for prior long-term BP control in these patients.

Inner retinal layers’ alterations and microvasculature changes after vitrectomy for rhegmatogenous retinal detachment

To examine the retinal layers' changes and alterations in retinal microvasculature in patients with rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy (PPV). Participants in this study were 103 patients with RRD, 85 macula off and 18 macula on, who were treated with PPV and gas tamponade without internal limiting membrane peeling, in two centers. All participants underwent best corrected visual acuity measurement, slit-lamp examination, fundoscopy, spectral domain-optical coherence tomography and optical coherence tomography angiography at week 5 and at month 6 postoperatively. The fellow untreated eyes were also examined and served as control data. A statistically significant enlargement in foveal avascular zone (FAZ) in both superficial capillary plexus (SCP) and deep capillary plexus (DCP) was noticed 5weeks postoperatively in patients with RRD treated with PPV compared to the fellow eyes and remained 6months after surgery. The FAZ enlargement in the operated eyes was accompanied with a statistically significant thinning of the inner retinal layer. In addition, there was a significant decrease in foveal and parafoveal vessel density (VD) in both SCP and DCP in the operated eyes compared to control eyes at week 5 postoperatively, which also remained at postoperative month 6. The study demonstrated that patients with RRD treated with PPV presented changes in the retinal microvasculature in both SCP and DCP, including enlargement of FAZ and decrease in VD. These changes seemed to be associated with inner retinal layer thinning.

Evaluation of the retinal layers and microvasculature in patients with acromegaly: a case-control OCT angiography study.

The aim of study was to evaluate the retinal layers and macular capillary network with OCTA in acromegaly patients, to compare with healthy population. In this prospective, observational, and comparative study, 40 acromegaly patients and 40 healthy control participants were included. Serum IGF-1 levels and disease duration of all patients were noted. Macular layers and angiography scanning was performed with a Zeiss Cirrus 5000 OCTA system. Macular thickness, RNFL, and GC-IPL values were obtained. For central vessel and perfusion density, central 6 mm was obtained and was evaluated by dividing into three groups (inner, outer, full). FAZ parameters were evaluated dividing into three groups (area, perimeter, circularity index). Analysis of the data was performed with the SPSS for Windows. There was no significant difference between the patient group and the control group in terms of age, gender, best corrected visual acuity (BCVA), spherical equivalent (SE), intraocular pressure (IOP), and axial length (AL). The mean follow-up period after diagnosis was 11.0 ± 5.5 years. Central and mean macular thicknesses were also significantly higher in the acromegaly group (p < 0.05). Superior, inferior, and average RNFL thicknesses were also significantly thinner in the acromegaly group (p < 0.05). When OCTA parameters were compared between groups, there was a significant decrease in central vessel density (CVD) and central perfusion density (CPD) values in all regions in acromegaly group compared with controls (p < 0.05). Our findings with OCTA show that acromegaly causes a significant capillary network decrease according to the healthy subjects.

Is there a relationship between hypoparathyroidism and retinal microcirculation?

To investigate the retinal microvasculature in patients with surgically induced hypoparathyroidism who have no clinical evidence of retinopathy and to compare these data with those of healthy control subjects. Forty patients with a confirmed diagnosis of permanent hypoparathyroidism and no clinical evidence of retinopathy and 37 age- and sex-matched healthy control subjects were included in the study. After complete ophthalmological examination, all patients underwent optical coherence tomography angiography measurement (Optovue Inc., Fremont, California, USA) to assess the foveal avascular zone (FAZ) area; FAZ perimeter; acircularity index of FAZ; foveal density-300; radial peripapillary capillary plexus (RPCP) vessel density; superficial, middle and deep capillary plexus vessel densities (SCP, MCP and DCP). The data from the right eyes of all participants were used for statistical analysis. The SCP and MCP vessel densities were significantly lower, and the RPCP whole image and peripapillary vessel densities were significantly higher than those in healthy control subjects (p < 0.05 for all). The DCP vessel densities of patients with surgically induced hypoparathyroidism were not significantly different from those of healthy control subjects (p > 0.05 for all). No significant difference was found in the FAZ area, FAZ perimeter, acircularity index of FAZ, foveal density-300 measurements between patients and controls (p > 0.05 for all). Reduced retinal vessel density in patients with surgically induced hypoparathyroidism supports the hypothesis that parathyroid hormone is associated with regulation of vascular homeostasis, including macular microcirculation. Increased perfusion in the peripapillary area may suggest an early subclinic effect of hypoparathyroidism.

Analysis of Foveal Microvascular Abnormalities in Patients with Systemic Lupus Erythematosus Using Optical Coherence Tomography Angiography

ABSTRACT Purpose: To analyze the abnormalities of foveal microvasculature in patients with systemic lupus erythematosus (SLE). Methods: A cross-sectional study of 41 eyes of patients diagnosed with SLE and 40 eyes of healthy controls. Sections measuring 6 mm×6 mm centered on the fovea were obtained using optical coherence tomography angiography (OCTA). Results: The area and perimeter of foveal avascular zone (FAZ) in SLE patients were greater than those in controls (both p < .05). The parafoveal vessel densities in the deep capillary plexus (DCP) of SLE patients were significantly decreased than those in controls (p < .001). There was a negative correlation between SLE disease activity index and parafoveal vessel density in DCP (p < .05). Conclusion: Enlargement of the FAZ and decline of the parafoveal vessel density of DCP were revealed by OCTA in patients with SLE. Moreover, a negative correlation between parafoveal vessel density in DCP and disease activity index was detected in SLE patients.

Association Between Clinical Biomarkers and Optical Coherence Tomography Angiography Parameters in Type 2 Diabetes Mellitus.

PurposeTo investigate the clinical significance of the changes in the macular microvasculature in patients with diabetes mellitus type 2 without diabetic retinopathy.MethodsFifty-five patients with diabetes mellitus type 2 without diabetic retinopathy and 48 healthy individuals were enrolled in a prospective cross-sectional study. We identified the changes of optical coherence tomography angiography parameters (foveal avascular zone [FAZ] area and circularity, vessel density, and perfusion index) of the 6 × 6-mm macular scan. Correlation and multiple regression analyses were performed between optical coherence tomography angiography parameters and previously known diabetes mellitus type 2-related demographic and systemic characteristics, and serum biochemical markers.ResultsFAZ parameters and perfusion index of the superficial and deep vascular plexus showed significant correlation with serum insulin level, and homeostasis model assessment indices. In multiple linear regression analysis, low insulin levels predicted increased FAZ areas in both the superficial (β = –0.007; P = 0.030) and deep layers (β = –0.010; P = 0.018) and a decreased perfusion index in the deep layer (β = 0.003; P = 0.001).ConclusionsThe expansion and loss of circularity of the FAZ and the decrease in the perfusion index may be affected by insulin resistance and secretory capacity in patients with diabetes mellitus type 2 with no diabetic retinopathy.

Retinal microvascular attenuation in mental cognitive impairment and Alzheimer's disease by optical coherence tomography angiography.

To explore regional variation of the macular microvasculature in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), also to detect the association between retinal macular microvascular parameters and the progress of preclinical AD. Prospective study of healthy controls, patients with MCI and patients with AD by using Optical coherence tomography angiography (OCT-A). We quantified foveal avascular zone (FAZ) areas, densities of the superficial retinal capillary plexuses (SRCP) and deep retinal capillary plexuses (DRCP). The SRCP and DRCP were divided into inner (3mm) and external (6mm) annular rings, each containing four quadrants (SI, II, TI, NI, SE, IE, TE and NE). The data were analysed statistically by using SPSS 22 software. Totally, 60 subjects including 21 HC (33 eyes), 21 patients with MCI (32 eyes) and 18 AD patients (28 eyes) were recruited. The microvascular densities of DRCP at all quadrants of the parafovea and perifovea were significantly lower in AD patients compared to HC group (p<0.05). Compared to the HCs, MCI patients showed significant microvascular loss in most sectors of the parafovea and the SE sector of the DRCP (p<0.05), but not in the parafovea (p=0.829) or perifovea (p=0.824) of the SRCP. No significant difference was found in microvascular density of SRCP among the groups, except at SI between the AD and HC groups (p=0.048). Our findings demonstrated the macular microvascular attenuation in MCI and AD patients. Both AD and MCI patients showed retinal microvascular density loss, which is more significant in the deep retinal capillary plexuses. Optical coherence tomography angiography (OCT-A) can be used to identify early microvascular abnormalities in AD and MCI. Quantified microvascular density in the DRCP might serve as potential biomarkers of early sign of AD then contribute to forestall the progression of preclinical AD.

Detection of retinal microvascular changes in von Hippel-Lindau disease using optical coherence tomography angiography.

PurposeVon Hippel-Lindau (VHL) disease is a hereditary disorder that can lead to ophthalmic manifestations, including retinal capillary hemangioma (RCH). The diagnosis of RCH is often guided by wide-field fluorescein angiography. In some cases, optical coherence tomography angiography (OCT-A) serves as a non-invasive alternative to FA. Herein, we used OCT-A to examine the macular microvasculature in patients with VHL disease.SubjectsSubjects were selected from patients with a diagnosis of VHL. The control group included eyes without retinal diagnosis from patients with an episode of unilateral retinal detachment or trauma and age ≤ 50 years old.MethodsSubjects were scanned on the Optovue RTVue-XR device to acquire 3mm x 3mm OCT-A images of the superficial (SCP) and deep capillary plexus (DCP). SCP and DCP vessel density (VD) were calculated after the images were binarized. Furthermore, for subjects with RCH, each OCT-A image was divided equally into four quadrants. SCP and DCP VD of quadrants with RCH were compared to those without RCH. T-tests were performed for statistical analysis.Results67 eyes with a history of VHL disease were included as study subjects, while 16 eyes were included as controls. Significant increases in VD were found in patients with VHL disease for both the SCP (p = 0.0441) and DCP (p = 0.0344). When comparing quadrants with associated RCH development to those without, we found no significant difference in SCP VD (p = 0.160) or DCP VD (p = 0.484).ConclusionsOCT-A can detect changes in the retinal microvasculature in the macula of patients with VHL disease. OCT-A imaging may be an additional tool for screening and early detection of patients at risk of developing ocular complications of VHL disease. Future studies should explore subtle progression on OCT-A associated with the pathogenesis and development of RCH, particularly with larger scan patterns.

The Detection of Retina Microvascular Density in Subclinical Aquaporin-4 Antibody Seropositive Neuromyelitis Optica Spectrum Disorders

Purpose: To use optical coherence tomography (OCT) and OCT angiography (OCT-A) to measure changes in the retinal structure and microvasculature of patients with aquaporin-4 antibody-positive, neuromyelitis optica spectrum disorder (NMOSD) with a history of optic neuritis (NMOSD+ON) and those without it (NMOSD–ON).Methods: A total of 27 aquaporin-4 antibody-positive NMOSD patients and 31 age- and gender-matched healthy control (HC) participants were included. In 27 NMOSD patients, 19 of them had a history of optic neuritis (ON) and 8 of them had no history of ON. Peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell and inner plexiform layer (GCIPL) thickness were measured by OCT. Radial peripapillary capillary density (RPCD) and macular superficial vessel density (MSVD) were measured by OCT-A. Comparisons of retinal structural and microvascular parameters between the cohorts were performed using generalized estimating equation (GEE) models. Diagnostic accuracy was evaluated by the area under the receiver operating characteristics curve (AROC).Results: In NMOSD+ON eyes, the GCIPL and pRNFL thicknesses, 48.6 ± 7.1 and 61.7 ± 25.1 μm, respectively, were significantly thinner than in HC eyes (P < 0.001 for both). However, in NMOSD–ON eyes, the GCIPL and pRNFL thicknesses were not significantly thinner than in HC eyes (P > 0.05 for both). In NMOSD+ON eyes, the RPCD and MSVD, 37.8 ± 7.1 and 36.7 ± 5.0%, respectively, were significantly less dense than HC eyes (P < 0.001 for both). Similarly, the RPCD and MSVD in NMOSD–ON eyes, 49.0 ± 2.8 and 43.9 ± 4.2%, respectively, were also less dense than in HC eyes (P < 0.029 for RPCD, P < 0.023 for MSVD). The highest AROC, 0.845 (sensitivity = 88.5%, specificity = 78.0%), was achieved by the logistic regression combination of all of the variables, i.e., pRNFL, GCIPL, RPCD, and MSVD.Conclusions: Retinal microvascular changes were present in NMOSD–ON eyes. The combination of retinal structural and microvascular parameters might be helpful to discriminate NMOSD–ON eyes from HC eyes.

Platelet Extracellular Vesicles Drive Inflammasome-IL-1β-Dependent Lung Injury in Sickle Cell Disease.

Rationale: Intraerythrocytic polymerization of Hb S promotes hemolysis and vasoocclusive events in the microvasculature of patients with sickle cell disease (SCD). Although platelet-neutrophil aggregate-dependent vasoocclusion is known to occur in the lung and contribute to acute chest syndrome, the etiological mechanisms that trigger acute chest syndrome are largely unknown.Objectives: To identify the innate immune mechanism that promotes platelet-neutrophil aggregate-dependent lung vasoocclusion and injury in SCD.Methods:In vivo imaging of the lung in transgenic humanized SCD mice and in vitro imaging of SCD patient blood flowing through a microfluidic system was performed. SCD mice were systemically challenged with nanogram quantities of LPS to trigger lung vasoocclusion.Measurements and Main Results: Platelet-inflammasome activation led to generation of IL-1β and caspase-1-carrying platelet extracellular vesicles (EVs) that bind to neutrophils and promote platelet-neutrophil aggregation in lung arterioles of SCD mice in vivo and SCD human blood in microfluidics in vitro. The inflammasome activation, platelet EV generation, and platelet-neutrophil aggregation were enhanced by the presence of LPS at a nanogram dose in SCD but not control human blood. Inhibition of the inflammasome effector caspase-1 or IL-1β pathway attenuated platelet EV generation, prevented platelet-neutrophil aggregation, and restored microvascular blood flow in lung arterioles of SCD mice in vivo and SCD human blood in microfluidics in vitro.Conclusions: These results are the first to identify that platelet-inflammasome-dependent shedding of IL-1β and caspase-1-carrying platelet EVs promote lung vasoocclusion in SCD. The current findings also highlight the therapeutic potential of targeting the platelet-inflammasome-dependent innate immune pathway to prevent acute chest syndrome.

Characteristics of the Foveal Microvasculature in Asian Patients with Dry Age-Related Macular Degeneration: An Optical Coherence Tomography Angiography Study

Purpose: To evaluate changes in the foveal microvasculature in patients with dry age-related macular degeneration (dry AMD) using optical coherence tomography angiography (OCTA). Methods: Eighty-three eyes with dry AMD and 83 age- and sex-matched normal eyes were enrolled. A 3 × 3 mm² OCTA (Zeiss HD-OCT 5000 with AngioPlex; Carl Zeiss Meditec, Dublin, CA, USA) scan was used to acquire images. Vessel density (VD), perfusion density (PD), and the foveal avascular zone (FAZ) of the superficial capillary plexus were analyzed. Results: The VD of the full area, central area, and inner ring of the dry AMD patients (18.61, 8.41, and 20.45, respectively) were significantly lower than those of the controls (20.06, 11.09, and 22.51, respectively). The PD of the full area, central area, and inner ring of the dry AMD patients (0.34, 0.15, and 0.37, respectively) were also significantly lower than those of the controls (0.36, 0.19, and 0.40, respectively). The FAZ area and perimeter in the dry AMD patients (0.29 mm² and 2.47 mm, respectively) were larger than those in the controls (0.23 mm² and 2.09 mm, respectively). The FAZ circularity index in the dry AMD patients was smaller than that in the controls (0.61 vs. 0.66). Using univariate linear regression, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), and ganglion cell-inner plexiform layer (GC-IPL) thickness were associated with both VD and PD of the full area. Using multivariate analysis, only GC-IPL thickness was significantly associated with the VD and PD of the full area (p = 0.001 and p = 0.004, respectively). Conclusions: OCTA revealed changes in the foveal microcirculation of patients with dry AMD. Age, BCVA, CMT, and GC-IPL thickness should be considered when analyzing the OCTA data of patients with dry AMD. GC-IPL thickness is particularly important during clinical evaluation of VD and PD in patients with dry AMD.

Analysis of retinal and choroidal microvasculature in systemic sclerosis: an optical coherence tomography angiography study

To investigate the retinal and choroidal microvasculature in patients with systemic sclerosis (SSc) who have no clinical evidence of retinopathy and to compare these structures with those of healthy control subjects. Forty-five patients with a confirmed diagnosis of SSc and no clinical evidence of retinopathy and 45 age- and sex-matched healthy control subjects were included in the study. After complete ophthalmological examination, all patients underwent optical coherence tomography angiography (OCTA) measurement (Optovue Inc., Fremont, California, USA) to assess the foveal avascular zone (FAZ) area; FAZ perimeter; acircularity index of FAZ; foveal density-300; superficial and deep capillary plexus vessel densities; and choriocapillaris flow area at 1, 2, and 3 mm radius. The data from the right eyes of all participants were used for statistical analysis. The superficial capillary plexus vessel density of the whole image, fovea, parafovea and perifovea, and the deep capillary plexus vessel density of the fovea were significantly lower than those in healthy control subjects (p < 0.05 for all). No significant difference was found in the FAZ area, FAZ perimeter, acircularity index of FAZ, foveal density-300 and choriocapillaris flow area measurements between patients and controls (p > 0.05 for all). We demonstrated the ability of OCTA to reveal early retinal microvascular alterations in patients with SSc without any clinical evidence of retinopathy. Reduced vessel density in SSc patients supports the hypothesis of widespread vascular injury, including ocular microcirculation.

Decreased resting coronary flow and impaired endothelial function in patients with vasospastic angina.

Coronary endothelial and circulatory dysfunction plays important roles in the pathogenesis of vasospastic angina (VSA). However, a complete understanding of the entire coronary circulation including microvasculature in patients with VSA is lacking. A total of 32 patients without obstructive coronary artery disease in the left descending coronary artery, who underwent an intracoronary acetylcholine (ACh) provocation test for diagnosis of VSA, were enrolled prospectively. A positive diagnosis of the ACh test was defined as total/subtotal coronary artery narrowing accompanied by chest pain and/or ischemic ECG changes. Angina frequency and severity at baseline, and 1 and 3 months were recorded. Coronary circulation was evaluated invasively using a thermodilution method by obtaining the mean transit time (Tmn) at rest and hyperemia, coronary flow reserve, and index of microcirculatory resistance. Systemic endothelial function was assessed by the reactive hyperemia index. There were 14 (44%) and 18 (56%) patients with and without a positive ACh provocation test. The baseline characteristics did not differ significantly between the two groups. Patients with VSA had a significantly lower reactive hyperemia index compared with those without VSA (1.70±0.33 vs. 2.12±0.53, P=0.02). Coronary flow reserve, index of microcirculatory resistance, and hyperemic Tmn were not different between the two groups, whereas resting Tmn was significantly longer in patients with VSA (1.20±0.44 vs. 0.71±0.37, P=0.002). Although the frequency and severity of angina improved from baseline to 1 and 3 months in patients with both positive and negative ACh tests, there was no difference between the two groups. Patients with VSA had decreased resting coronary flow and impaired endothelial function.

Cutaneous microangiopathy in patients with type2 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy.

Aims/IntroductionTo examine the three‐dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type 2 diabetes in relation to neuropathy, retinopathy and nephropathy.Materials and MethodsThe present study enrolled 17 individuals with type 2 diabetes and 16 without. Skin sections were double‐immunostained for type IV collagen and VEGF‐A or protein gene product 9.5. Projected images from confocal microscopy served to quantify the occupancy rate of subepidermal type IV collagen‐immunoreactive microvascular basement membrane area (OR‐T4MBM), subepidermal VEGF‐A‐immunoreactive area and the VEGF/T4MBM ratio, as well as the protein gene product 9.5‐immunoreactive intraepidermal nerve fiber density. Reduced intraepidermal nerve fiber density was applied for the diagnosis of neuropathy, fundic ophthalmoscopy and fluorescein angiography for retinopathy, and microalbuminuria or persistent proteinuria for nephropathy.ResultsA total of 12 patients with diabetes had neuropathy, 10 had retinopathy and eight had nephropathy. Regardless of the presence or absence of neuropathy, retinopathy or nephropathy, OR‐T4MBM was significantly increased in patients with diabetes compared with individuals without diabetes. In contrast, VEGF/T4MBM ratio was significantly decreased in those with neuropathy and retinopathy, as well as in those with and without nephropathy, whereas a trend toward a decreased VEGF/T4MBM ratio was seen in patients without retinopathy, as compared with individuals without diabetes.ConclusionsThe present study is the first report to show that cutaneous microangiopathy, as indicated by subepidermal microvascular proliferation and impaired VEGF expression, appears to occur before the development of overt clinical neuropathy, retinopathy or nephropathy in patients with type 2 diabetes.

Correlating Changes in the Macular Microvasculature and Capillary Network to Peripheral Vascular Pathologic Features in Familial Exudative Vitreoretinopathy

To evaluate the macular microvasculature in patients with familial exudative vitreoretinopathy (FEVR) using OCT angiography (OCTA) and to assess for peripheral vascular changes using widefield fluorescein angiography (WFA). Multicenter, retrospective, comparative, observational case series. We identified 411 patients with FEVR, examined between September 2014 and June 2018. Fifty-seven patients with FEVR and 60 healthy controls had OCTA images of sufficient quality for analysis. Custom software was used to assess for layer-specific, quantitative changes in vascular density and morphologic features on OCTA by way of vessel density (VD), skeletal density (SD), fractal dimension (FD), vessel diameter index (VDI), and foveal avascular zone (FAZ). Widefield fluorescein angiography images were reviewed for peripheral vascular changes including capillary dropout, late-phase angiographic posterior and peripheral vascular leakage (LAPPEL), vascular dragging, venous-venous shunts, and arteriovenous shunts. Macular microvascular parameters on OCTA and peripheral angiographic findings on WFA. OCT angiography analysis of 117 patients (187 eyes; 92 FEVR patients and 95 control participants) demonstrated significantly reduced VD, SD, and FD and greater VDI in patients with FEVR compared with controls in the nonsegmented retina, superficial retinal layer (SRL), and deep retinal layer (DRL). The FAZ was larger compared with that in control eyes in the DRL (P < 0.0001), but not the SRL (P= 0.52). Subanalysis by FEVR stage showed the same microvascular changes compared with controls for all parameters. Widefield fluorescein angiography analysis of 95 eyes (53 patients) with FEVR demonstrated capillary nonperfusion in all eyes: 47 eyes (49.5%) showed LAPPEL, 32 eyes (33.7%) showed vascular dragging, 30 eyes (31.6%) had venous-venous shunts, and 33 eyes (34.7%) had arteriovenous shunts. Decreasing macular VD on OCTA correlated with increasing peripheral capillary nonperfusion on WFA. Decreasing fractal dimension on OCTA correlated with increasing LAPPEL severity on WFA. Patients with FEVR demonstrated abnormalities in the macular microvasculature and capillary network, in addition to the peripheral retina. The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA.