Capillary Perfusion Density Research Articles

Quantitative Microvascular Analysis With Wide-Field Optical Coherence Tomography Angiography in Eyes With Diabetic Retinopathy

Wide-field optical coherence tomographic angiography (OCTA) may provide insights to peripheral capillary dropout in eyes with diabetic retinopathy (DR). To describe the diagnostic performance of wide-field OCTA with and without large vessel removal for assessment of DR in persons with diabetes. This case-control study was performed from April 26, 2018, to April 8, 2019, at a single tertiary eye center in Singapore. Case patients were those with type 2 diabetes for more than 5 years and bilateral DR diagnosed by fundus imaging; control participants included those with no self-reported history of diabetes, a fasting glucose level within the normal range in the past year, and no ocular pathologic findings. A wide-field (12 × 12-mm2) fovea-centered scan was performed using a prototype swept source OCTA system. Retinal microvasculature was examined by separating the angiograms into large vessels, capillaries, and capillary dropout regions. Area under the receiver operating characteristic curve (AUC) for DR severity discrimination using wide-field vascular metrics. Retinal perfusion density (RPD), capillary perfusion density (CPD), large vessel density (LVD), and capillary dropout density (CDD) were calculated. Low-contrast regions were excluded from the calculation. A total of 49 eyes in 27 control participants (17 male [63.0%]; mean [SD] age, 59.96 [7.63] years; age range, 44-79 years) and 76 eyes in 47 patients with diabetes (29 male [61.7%]; mean [SD] age, 64.36 [8.08] years; range, 41-79 years) were included. Among eyes in patients with diabetes, 23 were in those with diabetes but no DR, 25 in those with mild nonproliferative DR, and 28 in those with moderate to severe nonproliferative DR. There was no difference in RPD, CPD, LVD, and CDD between the control group and the group with diabetes and no DR. There was a stepwise decrease in RPD, CPD, and CDD in the diabetes with no DR, mild nonproliferative DR, and moderate to severe nonproliferative DR groups, whereas LVD was not associated with DR staging. The nonproliferative DR group had decreased RPD, CPD, and CDD compared with the control group. The CPD had higher AUCs than RPD for discriminating diabetes with nonproliferative DR (combined mild and moderate to severe nonproliferative DR) vs no DM (AUC, 0.92 [95% CI, 0.87-0.98] vs 0.89 [95% CI, 0.83-0.95], P = .01), diabetes with no DR vs mild nonproliferative DR (AUC, 0.81 [95% CI, 0.68-0.94] vs 0.77 [95% CI, 0.64-0.91], P = .18), and mild nonproliferative DR vs moderate to severe nonproliferative DR (AUC, 0.82 [95% CI, 0.71-0.94] vs 0.78 [95% CI, 0.65-0.91], P = .01) but similar AUCs for no DM vs diabetes with no DR. The total perfusion density and CPD in wide-field OCTA had better discriminative power than the central 6 × 6-mm2 field (CPD, 0.89 [95% CI, 0.83-0.95] vs 0.84 [95% CI, 0.77-0.92], P = .06; total perfusion density, 0.93 [95% CI, 0.87-0.98] vs 0.90 [95% CI, 0.83-0.96], P = .06). The findings suggest that wide-field OCTA provides information on microvascular perfusion and may be useful for detecting predominant peripheral capillary dropout in eyes with nonproliferative DR. A vascular selectivity approach excluding the large vessels may improve the discriminative power for different stages of DR.

Biomarkers of diabetic retinopathy on optical coherence tomography angiography

Pathogenesis of diabetic retinopathy (DR) is complex and multifactorial, giving rise to a wide range of potential biomarkers - quantitatively and objectively measurable indicators of the biological, pathological processes or pharmacological response to therapy. This non-systemic review is devoted to a vital problem - possibility of using biomarkers acquired with optical coherence tomography angiography (OCTA-biomarkers) in DR. The review examines the qualitative and quantitative indicators obtained using OCTA as potential biomarkers of DR. Of greatest interest is the assessment of diabetic microvascular abnormalities such as microaneurysms, intraretinal microvascular abnormalities, neovascularization and non-perfusion (ischemia) zones. A separate section is devoted to currently well-studied indices reflecting the area and regularity of the foveolar avascular zone, and microcirculation indices such as capillary perfusion density, blood flow indices, fractal dimension of retinal microcirculation vessels, etc. The relationship of OCTA-biomarkers and diabetic macular edema is also discussed. Biomarkers obtained with wide-field OCTA, such as indices quantitatively reflecting ischemia and neovascularization are paid special attention in the review. The problems and solutions associated with the use of OCTA-biomarkers in DR are also considered. In general OCTA-biomarkers in DR are becoming an important tool for screening, diagnosis, monitoring of DR, and for predicting and preventing patients' clinical response to treatment.

Changes in retinal and choriocapillaris density in diabetic patients receiving anti-vascular endothelial growth factor treatment using optical coherence tomography angiography

BackgroundOptical coherence tomography angiography (OCTA) enables detailed, non-invasive assessment of ocular vasculature. This study uses OCTA imaging to evaluate choriocapillaris and retinal capillary perfusion density (CPD) changes in diabetic retinopathy following anti-vascular endothelial growth factor (VEGF) treatment.MethodsRecords of 38 eyes at a single institution were reviewed, grouped as non-diabetic controls (19 eyes), diabetes mellitus patients with diabetic retinopathy (DR, 19 eyes) and macular edema (DME). DR eyes were imaged at baseline, 6-months and 12-months after anti-VEGF treatment. Quantitative analyses assessed CPD of the choriocapillaris and retinal plexus.ResultsDR eyes showed decreased choriocapillaris whole-image CPD (62.6 ± 6.1 vs. 68.4 ± 5.1, p < 0.003), foveal CPD (61.2 ± 7.4 vs. 66.3 ± 9.8, p < 0.014), and parafoveal CPD (61.9 ± 6.6 vs. 68.2 ± 4.8, p < 0.002) at baseline. DR eyes also showed decreased retinal density, including whole-image CPD (46.9 ± 5.1 vs. 50.7 ± 5.6, p < 0.04), foveal CPD (27.6 ± 5.9 vs. 34.1 ± 6.1, p < 0.002), and parafoveal CPD (49.0 ± 5.6 vs. 53.1 ± 6.0, p < 0.011). Following 12 months of anti-VEGF treatment, no changes to retinal or choriocapillaris or CPD were observed. Retinal central subfield thickness decreased (397.1 ± 93.2 µm vs. 294.2 ± 71.5 µm, p < 0.005). Lastly, FAZ area (0.307 ± 0.133 mm2 vs. 0.184 ± 0.058 mm2, p = 0.008) and perimeter (2.415 ± 0.692 mm2 vs. 1.753 ± 0.408 mm2, p = 0.002) were increased in DR eyes at baseline. No changes to FAZ area or perimeter were seen with anti-VEGF treatment in DR eyes.ConclusionsCompared to control, choriocapillaris and retinal CPD are reduced in DR, while FAZ area and perimeter are increased. No retinal capillary or choriocapillaris CPD changes were observed in DR eyes following anti-VEGF treatment.

Effectiveness of Deresuscitation With Central Venous Pressure Target 0-4 mmHg on Capillary Perfusion Density, AKI Stage, Cardiac Index, and the ICU Length of Stay in Septic Shock Patients After Resuscitation

Effectiveness of Deresuscitation With Central Venous Pressure Target 0-4 mmHg on Capillary Perfusion Density, AKI Stage, Cardiac Index, and the ICU Length of Stay in Septic Shock Patients After Resuscitation

Multimodal Imaging Assessment of Vascular and Neurodegenerative Retinal Alterations in Type 1 Diabetic Patients without Fundoscopic Signs of Diabetic Retinopathy.

The aim of this cross-sectional case-control study is to investigate the possible presence of vascular/neurodegenerative alterations in the retina of type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy (DR). Thirty-four eyes of 34 consecutive T1DM without DR (mean age 21 ± 2 years) were included. Another cohort of 27 eyes (27 healthy control subjects matched with age and sex) was also recruited. All patients underwent multimodal imaging evaluation using structural optical coherence tomography (OCT), OCT-angiography (OCT-A), dynamic vessel analyzer (DVA) and microperimetry. No significant differences were disclosed comparing diabetics and controls for visual acuity, central macular thickness, and subfoveal choroidal thickness. On retinal nerve fiber layer and ganglion cell complex thickness, no significant differences were disclosed comparing each 3-mm-diameter macular and peripapillary subfield between two groups. Using OCT-A, deep capillary plexus perfusion density (PD) of diabetics was significantly lower compared to control group, whereas PD of other retinal/choriocapillaris plexuses and foveal avascular zone area did not show any significant difference. Using DVA, diabetic eyes revealed a significantly decreased vessel response to flicker light in comparison to controls. No differences were disclosed using microperimetry analysis. Taken together, these results suggest that vascular alterations could be the first detectable retinal change in the development of DR.

Multimodal Analysis of Hyperautofluorescent Ring Size in Retinitis Pigmentosa.

To determine if a correlation exists between hyperautofluorescent ring size with visual acuity (VA), foveal avascular zone (FAZ) size, and retinal capillary perfusion density (CPD) in retinitis pigmentosa (RP). Eighteen eyes from nine patients with RP were imaged using fundus autofluorescence (AF) to identify autofluorescence defects, and hyperautofluorescent ring size was measured with an image-processing program. Spectral-domain optical coherence tomography angiography was used to measure FAZ area and calculate parafoveal CPD in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) using both a 3 mm × 3 mm and 6 mm × 6 mm strategy. The area of hyperautofluorescence was not strongly correlated with SCP perfusion density (P = .74), DCP perfusion density (P = .25), FAZ area (P = .14), or VA (P = .33). The area of the hyperautofluorescent ring does not correlate with VA, retinal CPD, or FAZ area. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:492-496.].

Diabetic macular edema treated with intravitreal aflibercept injection after treatment with other anti-VEGF agents (SWAP-TWO study): 6-month interim analysis

BackgroundDiabetic macular edema (DME) is an important cause of vision loss and despite the anatomical and functional improvement achieved with treatment, there are reports of persistent DME regardless of continuous anti-VEGF therapy. The purpose of this study is to examine the effect of patients with DME previously treated with other anti-VEGF agents who are transitioned to intravitreal aflibercept (IAI) on a fixed dosing regimen.MethodsThis prospective study included 20 patients presenting with DME with a history of previous anti-VEGF treatment with ranibizumab or bevacizumab. Patients received a 2 mg (0.05 mL) IAI every 4 weeks until no evidence of fluid by optical coherence tomography (OCT) followed by a fixed dosing schedule of 2 mg IAI once every 8 weeks through 24 months. There was a pre-planned interim analysis of the mean absolute change from baseline central foveal thickness at month 6 as measured by OCT. Secondary outcomes included mean change from baseline in ETDRS visual acuity and anatomic parameters. Optical Coherence tomography angiography (OCTA) capillary perfusion density (CPD) after transitioning to IAI therapy were also reported.ResultsAverage central subfield thickness on OCT at baseline was 419.7 ± 92.0 and improved to 303.8 ± 73.1 at 6-months (p < 0.001). At 6 months after IAI treatment, BCVA increased + 1.5 letters from baseline (p = 0.38). OCTA CPD analysis revealed significant increase from baseline in the foveal avascular zone in non-proliferative diabetic retinopathy group (p = 0.02).ConclusionsPatients with prior anti-VEGF therapy who were transitioned to IAI therapy revealed significant anatomic improvements through 6 months.Trial registration Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab (SwapTwo), Trial registration number: NCT02559180. Date of registration: September 24, 2015.https://clinicaltrials.gov/ct2/show/NCT02559180

Reduced vascular perfusion density in idiopathic epiretinal membrane compared to macular pseudohole.

To investigate the retinal capillary perfusion density by means of optical coherence tomography angiography (OCT-A) in idiopathic epiretinal membrane (ERM) and macular pseudoholes (MPH). This observational cross-sectional study examined consecutive patients affected by ERM and MPH presenting between June 2017 and December 2017, as well as the 30 eyes of 30 healthy subjects. All patients underwent swept-source OCT-A examination. For each patient, vessel perfusion density and foveal avascular zone (FAZ) area were measured. Twenty-five eyes of 20 patients with ERM and 28 eyes of 24 patients with MPH were enrolled. Thirty eyes of 30 age-matched healthy controls were included. The perfusion density in the superficial capillary plexus (SCP) of ERM (0.401 ± 0.012) turned out to be inferior that MPH (0.419 ± 0.018) and controls (0.415 ± 0.017) (p < 0.01), while no significant differences were evident among the three subgroups in the deep capillary plexus (DCP) (p = 0.1). The FAZ area in the SCP was smaller in the ERM group (0.168 ± 0.123mm2), respectively, than MPH (0.295 ± 0.013mm2) and controls (0.213 ± 0.107mm2) (p < 0.01), otherwise no difference were noted in the DCP (p = 0.14). OCT-A morphological features differ between idiopathic ERM and MPH, showing lower perfusion density in idiopathic ERM compared to MPH.

Reduced perfusion density of superficial retinal capillary plexus after intravitreal ocriplasmin injection for idiopathic vitreomacular traction

BackgroundTo investigate, using optical coherence tomography angiography (OCT-A), changes in perfusion density and in the foveal avascular zone (FAZ) in eyes with idiopathic vitreomacular traction (VMT) after ocriplasmin injection.MethodsIn this pilot study, we enrolled sixteen VMT eyes treated with intravitreal ocriplasmin injection. Sixteen healthy eyes were considered as controls. Macular perfusion density in 3 plexuses [superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC)] was calculated at baseline and at 1 month after injection.ResultsAfter injection, VMT anatomically resolved in 9 eyes (56.2%), whereas 7 eyes (43.8%) achieved an incomplete VMT separation. Superficial capillary plexus perfusion density was reduced significantly after injection (from 0.427 ± 0.027 to 0.413 ± 0.028; p = 0.0146), while no differences were noted in the DCP (p = 0.2717) nor in the CC (p = 0.6848). Study-eye perfusion density was statistically similar to control eyes in all three plexuses, both at baseline and at follow-up. The FAZ in the SCP area remained unchanged after injection (p = 0.168) but was significantly inferior to controls both at baseline and at 1 month (0.198 ± 0.074 vs. 0.196 ± 0.070; p = 0.007).ConclusionsEyes with VMT have a perfusion density comparable to healthy controls, but a smaller FAZ. After ocriplasmin injection the perfusion density in the SCP is reduced, regardless the anatomical success. Limited by the small sample size and the pilot nature of the study, we found microvascular changes after ocriplasmin injection, which may be due to retinal traction release.

Earliest Evidence of Preclinical Diabetic Retinopathy Revealed Using Optical Coherence Tomography Angiography Perfused Capillary Density

To compare perfused capillary density (PCD) in diabetic patients and healthy controls using optical coherence tomography angiography (OCTA). Forty controls, 36 diabetic subjects without clinical retinopathy (NoDR), 38 with nonproliferative retinopathy (NPDR), and 38 with proliferative retinopathy (PDR) were imaged using spectral-domain optical coherence tomography. A 3× 3-mm full-thickness parafoveal OCTA scan was obtained from each participant. Following manual delineation of the foveal avascular zone (FAZ), FAZ area, perimeter, and acircularity index were determined. Seven consecutive equidistant 200-μm-wide annular segments were drawn at increasing eccentricities from the FAZ margin. Annular PCD (%) was defined as perfused capillary area divided by the corresponding annulus area after subtraction of noncapillary blood vessel areas. Nonparametric Kruskal-Wallis testing with Bonferroni correction was performed in pairwise comparisons of group PCD values. The NoDR group demonstrated consistently higher PCD compared to the control group in all 7 annuli, reaching statistical significance (36.6% ± 3.30% vs 33.6% ± 3.98%, P= .034) at the innermost annulus (FAZ margin to 200μm out). The NPDR and PDR groups demonstrated progressively decreasing PCD. Differences in FAZ metrics between the NoDR and control groups did not reach statistical significance. Relative to healthy controls, increased PCD values in the NoDR group likely represent an autoregulatory response to increased metabolic demand, while the decrease in PCD that follows in NPDR and PDR results largely from an incremental loss of capillary segments. These findings, consistent with previous studies, demonstrate the potential of OCTA as a clinical tool for earlier objective detection of preclinical diabetic retinopathy. NOTE: Publication of this article is sponsored bythe American Ophthalmological Society.

Peripapillary Perfused Capillary Density in Exfoliation Syndrome and Exfoliation Glaucoma versus POAG and Healthy Controls: An OCTA Study.

To compare the peripapillary perfused capillary density (PCD) among eyes with exfoliation syndrome (XFS), exfoliation glaucoma (XFG), primary open-angle glaucoma (POAG), and controls. Observational, cross-sectional study. Optical coherence tomography angiography (OCTA) images (4.5×4.5 mm) of the optic nerve head were obtained using a commercial spectral domain OCTA system (AngioVue Avanti RTVue-XR, OptoVue, Fremont, CA). Two concentric circles with 1.95-mm (inner) and 3.45-mm (outer) diameters were placed manually, producing an annulus of width 0.75 mm centered at the optic disc. PCD was calculated as the ratio of pixels associated with capillaries to the pixels in the annulus after large blood vessel removal. Continuous variables were assessed by analysis of variance and Tukey honest significant difference (HSD) test. Multiple linear regression analysis was performed to adjust for confounding factors. Forty-three XFG eyes, 31 POAG eyes matched for visual field mean deviation, 33 XFS eyes, and 45 control eyes were analyzed. PCD demonstrated a progressive decrease from controls to XFS to POAG to XFG. Pairwise comparisons revealed significant differences in PCD between each pair of groups (all P<0.01) except for PCD between XFS and POAG (P = 0.08). A multivariable model adjusting for age and stage showed a more significant decrease in PCD in XFG compared with POAG (P = 0.001). PCD was more significantly decreased in XFG compared with POAG eyes and in XFS compared with control eyes. OCTA provides the first quantitative evidence of the microvascular disturbance that accompanies XFS.

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy.

Whether neural or vascular defects occur first in the early onset of diabetic retinopathy (DR) is undetermined. To investigate microcirculation and microstructure differences of optic nerve head (ONH) between diabetic eyes without clinically evident retinopathy and healthy controls using optical coherence tomography angiography (OCTA). Cross-sectional observational study. Sixty eyes of 60 patients with type 2 diabetes and without clinically evident retinopathy and 60 eyes of 60 age-matched healthy controls were included in this study. All participants underwent 4.5 × 4.5-mm rectangle scans centred on the ONH using OCTA (RTVue-XR Avanti; Optovue, Fremont, CA). Peripapillary retinal nerve fibre layer (RNFL) thickness and capillary perfusion density inside the ONH and in the peripapillary region were compared between the two groups. Vessel density values in both peripapillary and inside the disc were significantly lower in diabetic patients without DR compared to normal controls. The reduction of vessel density was prominent in all eight peripapillary sectors in diabetic eyes (all P < 0.05). Thinning of RNFL thickness was significant in the nasal superior (P < 0.001), inferior nasal (P = 0.023) and superior nasal quadrant (P < 0.001) in diabetic eyes in comparison to normal controls. ONH perfusion and peripapillary RNFL thickness were significantly decreased in preclinical DR patients compared to normal controls. Microvascular alterations in ONH may occur earlier than peripapillary RNFL defect in the course of DR.

Choriocapillaris and retinal vascular plexus density of diabetic eyes using split-spectrum amplitude decorrelation spectral-domain optical coherence tomography angiography.

Split-spectrum amplitude decorrelation angiography for spectral-domain optical coherence tomography has enabled detailed, non-invasive assessment of vascular flow. This study evaluates choriocapillaris and retinal capillary perfusion density (CPD) in diabetic eyes using optical coherence tomography angiography (OCTA). Records of 136 eyes that underwent OCTA imaging at a single institution were reviewed. Eyes were grouped as non-diabetic controls (37 eyes), patients with diabetes mellitus (DM) without diabetic retinopathy (DM without DR, 31 eyes), non-proliferative diabetic retinopathy (NPDR, 41 eyes) and proliferative diabetic retinopathy (PDR, 27 eyes). Quantitative CPD analyses were performed on OCTA images for assessing perfusion density of the choriocapillaris and retinal plexus for all patients and compared between groups. Eyes with NPDR and PDR showed significantly decreased choriocapillaris CPD compared with controls, while DM eyes without DR did not show significant change. Choriocapillaris whole-image CPD was decreased by 8.3% in eyes with NPDR (p<0.01) and decreased by 7.1% in eyes with PDR (p<0.01). Choriocapillaris parafoveal CPD was decreased by 8.9% in eyes with NPDR (p<0.01) and decreased by 8.2% in eyes with PDR (p<0.01). Compared with controls, only eyes with PDR showed significantly decreased retinal CPD, as well as significantly increased foveal avascular zone (FAZ) area. In those patients, retinal whole-image CPD was decreased by 9.7% (p<0.01), retinal foveal CPD was decreased by 20.5% (p<0.01) and retinal parafoveal CPD was decreased by 11.4% (p<0.01). FAZ area was increased by 50.9% (p<0.01). Choriocapillaris and retinal CPD are reduced in diabetic retinopathy, while FAZ area is increased in eyes with PDR. Vascular changes captured by new imaging modalities can further characterise diabetic choroidopathy.

Association of Myopia With Peripapillary Perfused Capillary Density in Patients With Glaucoma

This study used optical coherence tomographic angiography to assess for impaired blood flow in myopic eyes with or without open-angle glaucoma. To compare the peripapillary perfused capillary density (PCD) between eyes with and without glaucoma. In this cross-sectional study at a tertiary glaucoma referral practice, we recruited patients with myopic eyes of spherical equivalent of more than -3.0 diopters with and without open-angle glaucoma, patients with nonmyopic eyes with glaucoma, and patients with no disease from February 2016 to October 2016. We obtained 4.5 × 4.5-mm optical coherence tomographic angiography images of the optic nerve head and calculated PCD as the ratio of pixels associated with capillaries to the number of pixels in the region of interest after large blood vessel removal. Both eyes of each patient were used in the analysis. Continuous variables were assessed by analysis of variance and Tukey tests. A marginal model of generalized estimating equations was performed to adjust for confounding factors and intraclass correlations. Mean PCD. We matched 87 patients with myopic eyes with glaucoma (of whom 39 [45%] were women), 17 with myopic eyes without glaucoma (of whom 10 [59%] were women), and 93 with non-myopic eyes with glaucoma (of whom 55 [59%] were women) for visual field defects and included 51 control participants (or whom 38 [75%] were women). Mean (SD) ages were 67.5 (12.0) years for patients with myopia and glaucoma, 48.2 (19.0) years for those with myopia without glaucoma, 67.3 (11.0) years for those with glaucoma without myopia, and 64.7 (8.9) years in control participants. Global PCD demonstrated a progressive decrease from the control group (mean [SD], 41.0 [4.2]) to those with myopia without glaucoma (38.4 [5.8]) to those with glaucoma without myopia (31.9 [7.5]) to those with both (28.2 [6.0]; all P < .001). The mean difference in global PCD between the 3 groups and control group, adjusted for age and axial length, was greatest in those with myopia and glaucoma (-11.1; 95% CI, -14.0 to -8.1; P < .001), followed by those with glaucoma without myopia (-8.6; 95% CI, -10.9 to -6.3; P < .001) and those with myopia without glaucoma (-2.8; 95% CI, -6.9 to 1.2; P = .17). No interaction was found between glaucoma and myopia. These findings demonstrate peripapillary microvascular attenuation to a greater extent in open-angle glaucoma than myopia. The cross-sectional design means we cannot determine if this association is a cause and/or is associated with other confounding factors.

Optical Coherence Tomography Angiography in Diabetes.

Diabetic retinopathy is a progressive microvascular disease that leads to increased vessel permeability, retinal ischemia, and retinal neovascularization. Optical coherence tomography angiography (OCTA) is a novel angiography technique that has the capability to advance our understanding of diabetic eye disease by providing high-resolution images of retinal and choroidal microvasculature blood flow and structure. Using OCTA, the vascular changes of diabetic retinopathy including microaneurysms, retinal non-perfusion, intraretinal microvascular abnormalities, and neovascularization can be clearly visualized. OCTA offers several advantages over fluorescein angiography (FA) in that it is faster, safer, and non-invasive, allows better visualization of retinal vessels in both the superficial and deep capillary layers, and can provide quantitative measurements of areas of non-perfusion of the macula and nerve. OCTA capillary perfusion density maps and average perfusion density values provide an easy way to grade progressive vascular change. Despite these advantages, imaging with OCTA can only provide a limited view of the peripheral retina and is unable to demonstrate leakage, staining, or pooling. OCTA requires patients to maintain good fixation to obtain high-resolution images which can be a challenge for those with severe macular disease. In patients who cannot safely undergo FA, OCTA may serve as an alternative form of angiography that can be safely and more frequently performed for the management of diabetic retinopathy.

Optical Coherence Tomography Angiography Analysis of Perfused Peripapillary Capillaries in Primary Open-Angle Glaucoma and Normal-Tension Glaucoma.

To compare perfused peripapillary capillary density in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and normal patients using optical coherence tomography angiography (OCT-A). A retrospective review of POAG, NTG, and normal patients imaged with OCT-A was performed. En face OCT angiograms identifying peripapillary vessels were obtained using a spectral-domain OCT system (Avanti RTVue-XR). A custom image analysis approach identified perfused peripapillary capillaries, quantified perfused capillary density (PCD), and generated color-coded PCD maps for 3.5- and 4.5-mm-diameter scans. We compared PCD values, PCD maps, standard automated perimetry (Humphrey visual field [HVF]) parameters, and OCT retinal nerve fiber layer (RNFL) thickness analyses across all groups. Forty POAG, 26 NTG, and 26 normal patients were included. Annular PCD in POAG (34.24 ± 6.76%) and NTG (37.75 ± 3.52%) patients was significantly decreased compared to normal patients (42.99 ± 1.81%) in 4.5-mm scans (P < 0.01 and P < 0.01, respectively). Similar trends and statistical significances were seen in 3.5-mm scans. Linear regression analysis resulted in moderate correlations between annular PCD values and other glaucomatous parameters. Pearson coefficients comparing annular PCD from 4.5-mm scans in POAG and NTG groups to HVF mean deviation, HVF pattern standard deviation, and average RNFL thickness all showed statistical significance (P < 0.05). Color maps showed that POAG and NTG patients had a reduction of perfused capillaries that progressed in size when comparing early, moderate, and severe glaucoma groups. Optical coherence tomography angiography can uniquely identify changes in peripapillary PCD in glaucoma patients. Optical coherence tomography angiography may offer insights into the pathophysiology of glaucomatous damage and risk factors for disease progression.

Superficial and deep vascular structure of the retina in diabetic macular ischaemia: OCT angiography.

Diabetic macular ischaemia (DMI) is a major cause of visual loss in patients with diabetic retinopathy. Although the incidence is not well known, some clinical studies have reported an estimate of approximately 7% of all patients with diabetic retinopathy. The DMI is morphologically appreciable by means of fluorescein angiography (FA) that shows an enlargement of the foveal avascular zone (FAZ) as well as the interruption of capillaries all around the foveal region. However, FA needs dye injection to observe retinal circulation and might have significant adverse events ranging from discomfort and nausea to, in rare cases, anaphylaxis. Optical coherence tomography (OCT) has introduced a new method to visualize the retina by means of cross-sectional images with increased speed and sensitivity over time. This method, known as OCT angiography based on split spectrum amplitude decorrelation angiography (SSADA), is able to detect small changes in retinal vascular microcirculation (Jia et al. 2012). The SSADA has been successfully reported for retinal circulation assessment in healthy eyes (Savastano et al. 2015). The capillary perfusion density values in diabetic eyes were evaluated by Agemy et al. (2015). However, they reported limited information available about OCT angiography changes in DMI. The aim of this study was to evaluate the perifoveal vascular structure in DMI eyes using OCT angiography (OCT-A). Twenty eyes of 10 healthy subjects and 20 eyes of 20 DMI eyes were studied. The mean age of healthy subjects was 50.55 ± 11.07 years. The mean age of DMI patients was 59.5 ± 11.07 years. In DMI patients, the following clinical parameters were considered: diabetes duration (years), HbA1C (%), the presence of peripheral neuropathy involving the inferior and upper limbs, the grade of peripheral retinal ischaemia distributed into four quadrants assessed in FA, the maximum of serum glycaemia ever registered and body mass index (BMI). The OCT-A images and corresponding OCT B-scan were assessed in healthy and DMI eyes using an AngioVue system commercially available XR-Avanti SD OCT device (OptoVue, Freemont, CA, USA). All DMI eyes presenting macular ischaemia by FA were analysed by OCT-A for inclusion in this study, and all OCT-A images had to be of sufficient quality to allow visualization of ‘no flow area’ capillaries for grading of the severity of perifoveal vascular structure in healthy and DMI eyes. The protocol for analysis was SSADA in 3 × 3 mm2 scan volume centred on the foveal region. The automatic detection of ‘no flow area’ in healthy and diabetic eyes of the superficial vascular network (SVN) and deep vascular network (DVN) is shown in Figure 1. The perifoveal vascular structure in healthy eyes was 0.24 mm2 (±0.02) and 0.27 mm2 (±0.02) for the SVN and DVN, respectively, while in DMI eyes, the values were 0.35 mm2 (±0.03) and 0.46 mm2 (±0.02) for the SVN and DVN, respectively (difference by t-tests: p < 0.001), for both the SVN and DVN. Box plots of the changes in the DVN and SVN observed in DMI eyes compared to healthy eyes (T = −7.074; p < 0.001) are shown in Figure 2. In diabetic eyes, the mean FAZ by manual measurement performed by image j software (Version 1.49v, Wayne Rasband; National Institutes of Health, Bethesda, MD, USA; http://imagej.nih.gov/ij) in FA (as described by Conrath et al. 2005) and the extent of perifoveal vascular area by OCT-A did not show any significant differences (mean FAZ at FA: 0.264, SD: 0.054; mean perifoveal vascular area at OCT-A: 0.262, SD: 0.02). No significant correlations were found between perifoveal vascular area measurements and systemic clinical parameters, as well as visual acuity. The present study was a qualitative and quantitative assessment of DMI eyes compared to healthy eyes using AngioVue OCT-A imaging. Our study demonstrated the potential clinical usefulness of the AngioVue system, based on SSADA application, to assess the size and features of DMI in both the SVN and DVN. Optical coherence tomography angiography allows to visualize and assess the appearance of the superficial and deep capillary networks by a quantitative method. This new tool is not applicable to the FA. According to Spaide et al. (2015), FA does not allow separate evaluation of the FAZs of the SVN and DVN because the two networks are overlapped. The potential future application of the methods may be the early identification of perifoveal vascular structure enlargement in eyes with no evidence of DMI with FA and to evaluate this area during the clinical follow-up.

Increased arginase levels contribute to impaired perfusion after cardiopulmonary resuscitation.

The postcardiac arrest syndrome occurs after global hypoxia leading to microcirculatory impairment. Nitric oxide (NO) is a key molecule regulating microvascular function. The enzyme arginase has been suggested to modulate microvascular function by regulating NO metabolism. Therefore, we investigated whether arginase increases following global hypoxia and resuscitation and tested whether arginase inhibition influences altered microcirculation in resuscitated patients. To determine the effect of global hypoxia on circulating arginase levels, fourteen healthy subjects were exposed to hypoxia in a normobaric hypoxia chamber (FiO² = 9·9%). In addition, 31 resuscitated patients were characterized clinically, and arginase 1 was measured on days 1 and 3. In eight resuscitated patients, a microcirculatory analysis was performed using a sidestream darkfield microcirculation camera. Perfused capillary density (PCD) was recorded before and after sublingual incubation of N-omega-hydroxy-nor-l-arginine (nor-NOHA) alone or together with the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA). Circulating arginase 1 levels increased in healthy volunteers following global hypoxia in the hypoxic chamber (P < 0·01). In addition, arginase 1 levels were higher on day 1 (69·1 ± 83·3 ng/mL) and on day 3 (44·2 ± 65·6 ng/mL) after resuscitation than in control subjects (P < 0·001). Incubation of the sublingual mucosa with nor-NOHA increased microcirculatory perfusion (P < 0·001). This effect was inhibited by co-incubation with K-NMMA. Circulating arginase 1 levels are increased following exposure to global hypoxia and in patients who have been successfully resuscitated after cardiac arrest. Topical arginase inhibition improves microcirculatory perfusion following resuscitation. This is of potential therapeutic importance for the postcardiac arrest syndrome.

Conventional hemodynamic resuscitation may fail to optimize tissue perfusion: an observational study on the effects of dobutamine, enoximone, and norepinephrine in patients with acute myocardial infarction complicated by cardiogenic shock.

AimTo investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock.Methods and ResultsThirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥2.5 L.min−1.m−2 or mixed-venous oxygen saturation (SvO2) ≥70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9–10.2] vs. 11.4 [8.4–13.9] mm.mm−2; p<0.05), and norepinephrine tended to decrease PCD (9.8 [8.5–11.9] vs. 8.8 [8.2–9.6] mm.mm−2, p = 0.08). Fifteen patients (50%) died within 30 days after admission. Patients who had low final PCD (≤10.3 mm.mm−2; 64%) were more likely to die than patients who had preserved PCD (>10.3 mm.mm−2; mortality 72% vs. 17%, p = 0.003).ConclusionThis study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock.

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Introduction: Packed red blood cell transfusion (pRBC) is commonly used in the ICU setting to treat diminished tissue oxygen delivery. However, data supporting this therapy is limited, and pRBC’s are an independent risk factor for prolonged hospitalization and death. Direct observation and analysis of erythrocyte perfusion in tissue capillaries, through the use of sidestream darkfield imaging, may yield further insight into the utility of and indication for pRBC transfusion. Hypothesis: We hypthesized that that microvascular perfusion is improved with pRBC transfusion. Methods: Trauma and elective surgery patients requiring an ICU level of care due to receive pRBC’s were enrolled prior to transfusion after obtaining informed consent. Two-minute SDI imaging was obtained in order to measure the perfused capillary density (PCD) prior to, then one and three hours after transfusion. PCD measures underwent ANOVA analysis to detect a 5% difference between pre- and post-transfusion SDI values, with a p < 0.05 considered significant. Mean arterial pressure (MAP) and hemoglobin were serially analyzed in a similar fashion. Results: Thirteen patients were enrolled, who received an average of 1.4 +/-0.1 units of pRBC. PCD did not significantly change from the pre-transfusion baseline at the 1 hour reassessment, but increased at the 3 hour reassessment (F(2) = 7.1, p = 0.009) while MAP remained unchanged (F(2) = 0.02, p = 0.98). As expected, serum hemoglobin increased with transfusion (F(2) = 7.0, p = 0.005). Conclusions: Transfusion of pRBC’s did not initially alter capillary perfusion, but improved microvascular perfusion 3 hours post-transfusion.