Retinal Microvascular Perfusion Research Articles

Optical coherence tomography angiography reveals abnormal retinal vascular density and perfusion in patients with X-linked adrenoleukodystrophy: a cross-sectional study

PurposeX-linked adrenoleukodystrophy (XALD) can affect the eyes. Existing therapies are hampered by early quantitative examination methods. This study used an optical coherence tomography angiography system (OCTA) to investigate retinal microvascular density and perfusion in XALD patients.MethodsFifty-two patients and 47 age-matched controls were included in this cross-sectional study. The patients were divided into three groups (symptomatic, less symptomatic, and controls). We compared the foveal avascular zone area, vascular density and perfusion area at the superficial vascular complex (SVC) and deep vascular complex (DVC) of the peripapillary and macular between the groups. We correlated these measurements with scale scores.ResultsCompared with the controls, the symptomatic group had significantly lower vascular density in the superior nasal sector of the peripapillary SVC (MD − 4.940884; 95% CI − 9.655061 to − 0.226707; p = 0.036), lower vascular density (MD − 4.259225; 95% CI − 8.248627 to − 0.269823; p = 0.032) and lower perfusion area (MD − 0.180304; 95% CI − 0.337135 to − 0.023472; p = 0.018) in the peripheral ring superior quadrant of the macular SVC. Compared with the less symptomatic group, the symptomatic group exhibited a significantly lower vascular density (MD − 5.635483; 95% CI − 10.450009 to − 0.820957; p = 0.015) and perfusion area (MD − 0.063351; 95% CI − 0.116611 to − 0.010091; p = 0.013) in the superior nasal sector of the peripapillary SVC; lower vascular density (MD − 4.817846; 95% CI − 8.924294 to − 0.711399; p = 0.015) and perfusion area (MD − 0.202707; 95% CI − 0.369499 to − 0.035915; p = 0.011) in the peripheral ring superior quadrant of the macular SVC; and greater vascular density (MD 7.209401; 95% CI 0.818716–13.600086; p = 0.021) and perfusion area (MD 0.047320; 95% CI 0.001685–0.092956; p = 0.039) in the inferior nasal sector of the peripapillary DVC. Among the 52 patients, the expanded disability status score (EDSS) was moderately negatively correlated with the vascular density (p = 0.001) and perfusion area (p = 0.002) in the peripheral ring superior quadrant of the macular SVC.ConclusionChanges in retinal vascular density and perfusion exist in XALD patients and are correlated with disease severity. OCTA has the potential to monitor the progression of XALD.

Metabolic, Microvascular, and Structural Predictors of Long-Term Functional Changes Evaluated by Multifocal Electroretinogram in Type 1 Diabetes.

This study aimed to analyze the potential pathogenic connection between metabolic factors, photoreceptor cell rearrangements, retinal microvascular perfusion, and functional parameters through multifocal electroretinography (mfERG) in type 1 diabetes mellitus (DM1). This prospective observational cohort study enrolled DM1 patients (40.5 ± 9.1 years) with mild nonproliferative diabetic retinopathy followed for 4 years. Patients were subjected to multimodal imaging, which included color fundus photography, optical coherence tomography (OCT), OCT angiography, adaptive optics (AO), and mfERG. OCTA slabs were analyzed using ImageJ software (software version 2.3.0/1.53f) to calculate perfusion density (PD) at both superficial (SCP) and deep (DCP) capillary plexuses, as well as flow deficit percentage (FD%) at the choriocapillaris (CC). To calculate cone metrics on AO at the parafovea, including cone density (CD), linear dispersion index (LDi), and heterogeneity packing index (Hpi%) in the parafovea, the images were post-processed using a MATLAB algorithm. The mfERG P1 implicit time (IT) and N1-P1 response amplitude density (RAD) from R1 (foveal area), R2 (parafoveal area), and the unified rings R1 + R2 were evaluated. A total of 22 patients (22 eyes) were enrolled. No significant differences were noted in central mfERG amplitude and implicit time-averaged values (p > 0.05, all). The main factor influencing R1 IT was HbA1c, while R1 RAD was affected by Hpi and CC FD%. R1 + R2 IT was influenced by Hpi, LDi (p > 0.001, all), and modifications in the perfusion density in the SCP (p < 0.001) and DCP (p = 0.03) at the parafovea. In contrast, R1 + R2 RAD were associated with HbA1c (p = 0.02) and Hpi (p < 0.001). Microvascular changes and glucometabolic factors are key elements influencing the long-term morphofunctional alterations at the photoreceptor level in DM1.

Interpericyte Tunneling Nanotubes Are Nonuniformly Distributed in the Human Macula.

Pericyte-to-pericyte communication via interpericyte tunneling nanotubes (IP-TNTs) is an important mechanism by which spatial and temporal precision in neurovascular coupling is achieved. This study quantifies the distribution and morphologic characteristics of IP-TNTs in the normal human macula. Ultra high-resolution, three-dimensional microscopic imaging of 11 perfusion-labeled normal human donor eyes was performed. Immunofluorescent markers for collagen IV, glial fibrillary acidic protein, nuclei, α-smooth muscle actin and phalloidin were used to distinguish IP-TNTs from perfused/nonperfused capillaries and glia processes. IP-TNT length, diameter and density in each capillary plexus was quantified and compared. IP-TNTs were present in all capillary plexuses. IP-TNTs bridged capillary segments within and between capillary plexuses but did not connect capillaries to arterioles or venules. Mean length of IP-TNTs was 72.6 ± 39.5µm (range 14.0 to 202µm) and mean diameter was 1.0 ± 0.42µm. IP-TNT length was non-normally distributed with a right-skewed distribution and 43% were 'short' (<55µm). Diameters were greater in the "long" (1.13 ± 0.44µm) than "short" (0.82 ± 0.33µm; P < 0.001) IP-TNTs. Density of IP-TNTs was greater in the superficial vascular plexus (3.80 ± 0.69 per 500µm2) compared to the intermediate (1.85 ± 0.80 per 500µm2; P < 0. 0001) and deep capillary plexus (1.58 ± 0.84 per 500µm2; P < 0.0001). No significant difference in IP-TNT density was found between the four macula quadrants (P = 0.98). The distribution of IP-TNTs in the human macula is non-uniform and is associated with the compartmentalized nature of retinal energy consumption and microvascular perfusion. The nonuniform properties of IP-TNTs may predispose distinct vascular beds to injury in conditions such as diabetes.

Multi-Parametric Retinal Microvascular Functional Perfusion Imaging Based on Dynamic Fundus Fluorescence Angiography.

Retinal microvascular disease has caused serious visual impairment widely in the world, which can be hopefully prevented via early and precision microvascular hemodynamic diagnosis. Due to artifacts from choroidal microvessels and tiny movements, current fundus microvascular imaging techniques including fundus fluorescein angiography (FFA) precisely identify retinal microvascular microstructural damage and abnormal hemodynamic changes difficulty, especially in the early stage. Therefore, this study proposes an FFA-based multi-parametric retinal microvascular functional perfusion imaging (RM-FPI) scheme to assess the microstructural damage and quantify its hemodynamic distribution precisely. Herein, a spatiotemporal filter based on singular value decomposition combined with a lognormal fitting model was used to remove the above artifacts. Dynamic FFAs of patients (n = 7) were collected first. The retinal time fluorescence intensity curves were extracted and the corresponding perfusion parameters were estimated after decomposition filtering and model fitting. Compared with in vivo results without filtering and fitting, the signal-to-clutter ratio of retinal perfusion curves, average contrast, and resolution of RM-FPI were up to 7.32 ± 0.43 dB, 14.34 ± 0.24 dB, and 11.0 ± 2.0 µm, respectively. RM-FPI imaged retinal microvascular distribution and quantified its spatial hemodynamic changes, which further characterized the parabolic distribution of local blood flow within diameters ranging from 9 to 400 µm. Finally, RM-FPI was used to quantify, visualize, and diagnose the retinal hemodynamics of retinal vein occlusion from mild to severe. Therefore, this study provided a scheme for early and precision diagnosis of retinal microvascular disease, which might be beneficial in preventing its development.

Macular vascular density alteration patterns in paediatric optic neuritis patients with serum MOG antibody positivity detected by optic coherence tomography angiography

PurposeThe retinal microvascular network plays a crucial role in inflammatory injury in paediatric optic neuritis (PON) with serum MOG antibody positivity (MOG + PON). This study compared retinal microvascular densities and structural alterations in MOG + PON eyes with paediatric isolated optic neuritis (PION) eyes and followed up with the final best-corrected visual acuity (BCVA) after 6 months. MethodsA total of 29 children (52 eyes) with PON, including 15 MOG + PON cases (28 eyes), 6 PION cases (10 eyes), 2 neuromyelitis optica spectrum disorders associated PON(NMOSD-PON) cases (4 eyes), 6 MOG-associated disease (MOGAD) patients without ON-affected eyes (MOG + NPON) cases (10 eyes) and age- and gender-matched healthy controls (HCs) underwent superficial/deep retinal angiography density (SAD/DAD) by optical coherence tomography angiography (OCTA). Their BCVAs were followed up until 6 months after PON onsets. ResultsMOG + PON cases had better final BCVAs than PION and NMOSD-ON. MOG + PON (35.7 ± 10.3 %) and PION (40.1 ± 10.3 %) eyes experienced severe SAD reductions in contrast to MOGAD+NPON (48.7 ± 5.2 %) and HCs eyes (55.6 ± 8.2 %). However, DAD in MOG + PON eyes (48.5 ± 9.2 %) and MOG + NPON eyes (53.1 ± 3.3 %) increased compared to HC eyes (45.7 ± 9.6 %; p = 0.028 and 0.009, respectively). SAD reduction occurred in acute PON and was detected as early as 2 weeks after PON onset. ConclusionsMOG + PON eyes had better final BCVAs than PION eyes, which displayed superficial retinal microvascular perfusion reductions and deep microvascular perfusion increases. SAD could be a sensitive surrogate for PON attacks in children with MOGAD.

Effect of Intraorbital Mechanical Compression on Retinal Microvascular Perfusion in Quiescent Thyroid-Associated Ophthalmopathy Based on Ocular Biomechanics Measured by Corvis ST.

To analyze the correlation between orbital compliance and retinal vessel density (VD) based on dynamic Scheimpflug analyzer (Corvis ST) and optical coherence tomographic angiography (OCT-A). In this prospective observational study, 65 eyes of 44 patients with thyroid-associated ophthalmopathy (TAO) in quiescent stage were included (15 males and 29 females). The whole eye movement (WEM) was detected by Corvis ST. The superficial capillary plexus VD (SCP-VD) and deep capillary plexus VD (DCP-VD) were obtained by scanning the 3 × 3mm area around the fovea using OCT-A, while the peripapillary vessel density (ppVD) was obtained by scanning the 4.5 × 4.5mm area around the optic disk. Covariances including biomechanically corrected intraocular pressure (bIOP), axial length, age and gender were adjusted during data analysis. The mean WEM of the participants was 0.235 ± 0.066mm. The mean SCP-VD and DCP-VD in whole image were 46.20% ± 3.77% and 50.51% ± 3.96%; the mean whole pp-VD was 49.75% ± 2.01%. WEM was positively correlated with SCP-VD (r = 0.327, p = 0.01) and the whole pp-VD (r = 0.394, p < 0.01) after adjusting by gender, axial length (AL), age and bIOP, but it was not significantly correlated with DCP-VD (r = 0.072 p = 0.581). Increase in orbital pressure might reduce retinal microvascular perfusion. Our data suggest orbital mechanical compression may be an important cause of retinal VD changes in quiescent patients with TAO.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Characterization of retinal microvasculature and structure in atrial fibrillation.

Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF). This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion. A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (β coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (β coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; β coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (β coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05). This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

Reduction in retinal microvascular perfusion during migraine attacks.

To determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA). Migraine attacks commonly include visual symptoms, but the potential role of the retina in these symptoms is not well understood. OCTA is a rapid, non-invasive imaging technique that is used to visualize the retinal microvasculature with high spatial resolution in a clinical setting. In this study we used OCTA to quantify different features of the retinal vasculature in patients with migraine during and between attacks, as well as in healthy controls (HCs). We performed a prospective cohort study of 37 patients with migraine with aura (MA) (median [interquartile range, IQR] age of 37 [14] years, 86% female) and 30with migraine without aura (MO) (median [IQR] age of 37 [17] years, 77% female) and 20 HCs (median [IQR] age of 35 [7] years, 50% female). Macular OCTA scans were obtained for all participants for the interictal analysis. In 12 MA and eight MO, scans were captured both during and outside of migraine attacks and five HCs had initial and repeat scans. In addition to analyzing the morphology of the foveal avascular zone, we calculated the vessel flux index (VFI), which is an indicator of retinal perfusion and conventional metrics (such as vessel area density) in the foveal and parafoveal regions. There was a significant difference in the parafoveal VFI in the ictal state between the groups (p = 0.009). During migraine attacks there was a significant reduction in the parafoveal region VFI in MA (-7%, 95% confidence interval [CI] -10% to -4%; p = 0.006) and MO (-7%, 95% CI -10% to -3%; p = 0.016) from their interictal baseline as compared to the change between repeat scans in HCs (2%, 95% CI -3% to 7%). Interictally, there was a mean (standard deviation [SD]) 13% (10%) (p = 0.003) lower blood perfusion in the MA group as compared to the MO group in the foveal region (mean [SD] 0.093 [0.023] vs. 0.107 [0.021], p = 0.003). Interictal analysis also revealed higher circularity in the superficial foveal avascular zone in the MA group compared with the MO group (mean [SD] 0.686 [0.088] vs. 0.629 [0.120], p = 0.004). In addition, interictal analysis of the patients with MA or MO and unilateral headache showed increased retinal vascular parameters consistent with greater perfusion in the eye ipsilateral to the side of the pain as compared with the contralateral eye. These results indicate that perfusion is reduced in MA and MO in the parafoveal retina during the ictal period. Interictally, the foveal retina in MA has reduced perfusion when compared to the foveal retina in MO. Patients with unilateral headache showed interictal asymmetry of retinal perfusion between eyes. These results indicate that changes in retinal perfusion could be a part of migraine pathophysiology, and that distinct retinal vascular signatures identified with OCTA could represent biomarkers for migraine.

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

Macular Microvascular Perfusion Status in Hypertensive Patients with Chronic Kidney Disease.

To compare retinal microvascular perfusion between the eyes of hypertensive patients with and without chronic kidney disease (CKD), the vessel density (VD) and fractal dimension (FD) of the superficial (SVP) and deep retinal vascular plexus (DVP) were analyzed on 6 × 6 mm fovea-centered optical coherence tomography angiography (OCTA) images of patients with hypertension. The retina was divided into an inner ring (IR) and outer ring (OR) according to the Early Treatment of Diabetic Retinopathy Study grid. The glomerular filtration rate (GFR) was determined and CKD was diagnosed (GFR < 60 mL/min/1.73 m2). Ninety-six eyes from 52 patients with hypertension were included in this analysis. Twenty patients (n = 37 eyes) were diagnosed with CKD. The mean age was 69 ± 11.7 years and 60.4 ± 9.2 years in the CKD group and in the control group, respectively. The univariate model revealed a significant difference in VD between patients without and with CKD in the superficial IR (0.36 ± 0.03 vs. 0.34 ± 0.04, p = 0.03), the superficial OR (0.35 ± 0.02 vs. 0.33 ± 0.04, p = 0.02), the deep OR (0.24 ± 0.01 vs. 0.23 ± 0.02, p = 0.003), and the FD in the SVP (1.87 ± 0.01 vs. 1.86 ± 0.02, p = 0.02) and DVP (1.83 ± 0.01 vs. 1.82 ± 0.01, p = 0.006). After adjusting for age and sex, these differences did not remain statistically significant. Similar results were observed for the FD in the SVP and DVP. In our cohort, patients with hypertension and CKD did not differ from patients without CKD in regard to microvascular perfusion status in the macular area as assessed using OCTA.

Differences in rate of change of retinal structural and microvasculature parameters in parkinson’s disease compared to controls

AbstractBackgroundPrior cross‐sectional studies have revealed decreased macular perfusion density (PFD) and increased peripapillary PFD in Parkinson’s disease (PD). We assess longitudinal rate of change of retinal microvascular and structural parameters in PD vs controls with normal cognition.MethodSubjects were imaged using Zeiss Cirrus HD‐5000 AngioPlex. Those with confounding medical or ocular comorbidities were excluded. Superficial capillary plexus (SCP) PFD and vessel density (VD) were assessed within ETDRS 6×6 circle, inner ring, outer ring and 3×3 circle and inner ring. SCP foveal avascular zone (FAZ) area was assessed. PFD, VD, FAZ, peripapillary retinal nerve fiber layer (RNFL), ganglion cell‐inner plexiform layer (GCIPL), and central subfield thickness (CST) were measured at 2 time points 1 year apart. Rate of change per year was calculated. Generalized estimating equations analyzed associations between rate of change of imaging parameters and PD.Result74 eyes of 40 patients with PD (60% male, mean age 67.47.9 years) &amp; 149 eyes of 78 controls (28% male, mean age 70.35.8 years) were included. No demographic differences were observed between groups except higher proportion of females in controls (p = 0.001). PD had a greater decline in PFD in 6×6 circle (mean change per year = 0.021, control = 0.00, p = 0.001), 6×6 inner ring (PD = 0.018, control = 0.001, p = .007), 6×6 outer ring (PD = 0.022, control = 0.00, p = 0.001), 3×3 circle (PD = 0.016, control = 0.002, p&lt;.001), 3×3 inner ring (PD = 0.016, control = 0.002, p&lt;0.001). PD had greater decline in VD in 6×6 circle (mean change per year in PD = 0.72/mm, control = 0.054/mm, p = 0.006), 6×6 inner ring (PD = 0.636/mm, control = 0.048/mm, p = 0.03), 6×6 outer ring (PD = 0.746/mm, control = 0.054/mm, p = 0.005), 3×3 circle (PD = 0.939/mm, control = 0.006/mm, p&lt;0.001), 3×3 inner ring (PD = ‐0.942/mm, control = 0.013/mm, p&lt;0.001). PD had greater decrease in GCIPL (mean change per year in PD = 0.403µm, control = 0.128µm control, p = 0.01). There were no significant differences in rate of change in FAZ area, RNFL thickness, CST, and no significant differences in rate of change when stratified by PD severity.ConclusionPD may be associated with more rapid loss of retinal microvascular perfusion and vessel densities and more rapid thinning of GCIPL compared to normal aging in controls with normal cognition.

Retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery stenosis

PurposeTo investigate the relationship between retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery (ICA) stenosis.MethodsPatients with unilateral moderate or severe ICA stenosis(≥50%) from West China hospital, Sichuan university were consecutively and prospectively recruited enrolled in the current study. En face angiograms of the superficial vascular complex (SVC), deep vascular complex (DVC), superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were generated by automatic segmentation using swept-source optical coherence tomography angiography (SS-OCTA) to assess the retinal microvascular perfusion. The cerebral blood flow perfusion on bilateral middle cerebral artery territories measured at the basal ganglia level was assessed by brain computed tomography perfusion (CTP). CTP data were postprocessed to generate maps of different perfusion parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and permeability surface(PS). Relative perfusion parameters (rPS, rCBF, etc.) were calculated as the ratio of the value on the contralateral side to that on the ipsilateral side.ResultsIn the final analysis, 31 patients were included, of whom 11 patients had a moderate ICA stenosis (50–69%) and 20 with a severe ICA stenosis(≥70%). A total of 55 eyes were analyzed in the study, 27 eyes from the ipsilateral side (ie, side with stenosis) and 28 eyes from the contralateral side. In the patients with ICA stenosis, there was a strong correlation between the retinal microvascular perfusion of SVC with rCBV(B = 0.45, p = 0.03), rCBF(B = 0.26, p = 0.02) and rPS(B = 0.45, p < 0.001) after adjustment for age, sex and vascular risk factors. Similar correlations were also found between microvasculature in SVP and cerebral perfusion changes. There were no any significant associations of microvascular perfusion in both DVC and DCP with CTP parameters(all p > 0.05).ConclusionsRetinal perfusion changes in superficial vascular layer (SVC and SVP) were correlated with brain hemodynamic compromise in patients with unilateral moderate or severe ICA stenosis(≥50%). Given the limited size of our study, future studies with larger sample size are needed to confirm our findings.

Analysis of retinal vasculature changes in indirect traumatic optic neuropathy using optic coherence tomography angiography.

To assess the retinal vasculature alterations in indirect traumatic optic neuropathy (ITON) patients following craniofacial trauma by optic coherence tomography angiography (OCTA). Patients diagnosed of monocular ITON were recruited from August 2016 to May 2020. OCTA was performed using the AngioVue OCT-A system for two cube scans centered at the optic nerve head and fovea. OCTA data included thicknesses of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), as well as proportion of capillary perfusion and data were analyzed for correlation with post-injury timepoints: within 7, 8-30, 31-90, and 91-365d. A total of 73 ITON patients were studied. Significant thinning of RNFL and GCC layers and attenuation of microvascular perfusion were observed in ITON eyes as compared to contralateral unaffected eyes (for most of the analyzed sectors and quadrants, P<0.05). Without respect to surgical intervention and vision recovery, the decrease in retinal layer thicknesses and microvascular perfusion was time-dependent, and most significant within three months (P<0.001). ITON presents with time-dependent thinning of retinal layers and attenuation of microvasculature, indicating possible degeneration of retinal ganglion cells due to reduced retinal blood supply.

Functional optical coherence tomography at altitude: retinal microvascular perfusion and retinal thickness at 3,800 meters.

Cerebral hypoxia is a serious consequence of several cardiorespiratory illnesses. Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into cerebral hypoxia in critical illness. In addition, although sex-specific differences in cardiovascular diseases are strongly supported, few have focused on differences in ocular blood flow. We evaluated the retinal microvasculature in males (n = 11) and females (n = 7) using functional optical coherence tomography at baseline (1,130 m) (day 0), following rapid ascent (day 2), and prolonged exposure (day 9) to high altitude (3,800 m). Retinal vascular perfusion density (rVPD; an index of total blood supply), retinal thickness (RT; reflecting vascular and neural tissue volume), and arterial blood were acquired. As a group, rVPD increased on day 2 versus day 0 (P < 0.001) and was inversely related to [Formula: see text] (R2=0.45; P = 0.006). By day 9, rVPD recovered to baseline but was significantly lower in males than in females (P = 0.007). RT was not different on day 2 versus day 0 (P > 0.99) but was reduced by day 9 relative to day 0 and day 2 (P < 0.001). RT changes relative to day 0 were inversely related to changes in [Formula: see text] on day 2 (R2=0.6; P = 0.001) and day 9 (R2=0.4; P = 0.02). RT did not differ between sexes. These data suggest differential time course and regulation of the retina during rapid ascent and prolonged exposure to high altitude and are the first to demonstrate sex-specific differences in rVPD at high altitude. The ability to assess intact microvasculature contiguous with the brain has widespread research and clinical applications.NEW & NOTEWORTHY Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into consequence of cerebral hypoxia in critical illness. This study demonstrates dynamic regulation of the retina during rapid ascent and prolonged exposure to high altitude and is the first to demonstrate sex-specific differences in retinal microvasculature at high altitude. The ability to dynamically assess intact microvasculature contiguous with the brain has widespread research and clinical applications.

Evaluation of Retinal Microvascular Perfusion Changes in Patients with Celiac Disease

ABSTRACT Purpose We aimed to determine whether there are retinal microvascular changes in patients with celiac disease (CD). Methods A total of 30 patients with CD (group 1) and 30 healthy controls (group 2) were included in this study. AngioVue optical coherence tomography angiography (OCTA) device was used to evaluate the retinal microvascular structure. Results Some of the values of both optic nerve head (ONH) vessel density (VD) and radial peripapillary capillary VDs were found to be significantly lower in group 1 than in group 2. These 2 groups were similar except for one of the parameters of superficial capillary plexus VD (SCP-VD), whereas it was found that deep capillary plexus VD (DCP-VD) was lower in group 1 than in group 2 except for the foveal area. Conclusion It was determined that some VDs obtained from the ONH and DCP-VD obtained from most areas of the macular region were significantly lower.

Reduced Retinal Microvascular Perfusion in Patients With Stroke Detected by Optical Coherence Tomography Angiography.

Currently there is a shortage of biomarkers for stroke, one of the leading causes of death and disability in aging populations. Retinal vessels offer a unique and accessible “window” to study the microvasculature in vivo. However, the relationship between the retinal microvasculature and stroke is not entirely clear. To investigate the retinal microvascular characteristics in stroke, we recruited patients with stroke and age-matched control subjects from a tertiary hospital in China. The macular vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), foveal avascular zone (FAZ) metrics, and optical coherence tomography angiography (OCTA) measured optic disc VD were recorded for analysis. A total of 189 patients with stroke and 195 control subjects were included. After adjusting for sex, visual acuity, systolic and diastolic blood pressure, a history of smoking, levels of hemoglobulin (HbA1c), cholesterol, and high-density lipoprotein (HDL), the macular VD of SCP and DCP in all sectors was decreased in patients with stroke. In the stroke group, the VD around the FAZ and the VD of the optic disk were lower. Logistic regression found the parafovea-superior-hemi VD of DCP > 54.53% [odds ratio (OR): 0.169] as a protective factor of stroke. Using the integration of all OCTA parameters and traditional risk factors, the area under the receiver operating characteristic (AUC) curve of distinguishing patients with stroke was 0.962, with a sensitivity of 0.944 and a specificity of 0.871. Our study demonstrates that the retinal VD is decreased in patients with stroke independently of the traditional risk factors of stroke, which may shed light on the monitoring of stroke using the retinal microvascular parameters.

The vessel density of the superficial retinal capillary plexus as a new biomarker in cerebral small vessel disease: an optical coherence tomography angiography study.

Optical coherence tomography angiography (OCTA) is a novel and noninvasive technique for the quantitative assessment of retinal microvascular perfusion. Since the retinal and cerebral small vessels share similar embryological origins, anatomical features, and physiological properties, altered retinal microvasculature might provide a new perspective on the mechanisms of cerebral small vessel disease (CSVD). We aimed to evaluate retinal vessel density (VD) in patients with CSVD using OCTA and identify associations with cerebral magnetic resonance imaging (MRI) markers and cognitive function. We prospectively recruited 47 CSVD patients and 30 healthy controls (HCs) to participate in the study. All participants underwent OCTA to evaluate retinal microvascular perfusion. The VDs of the macular region in the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and foveal avascular zone (FAZ) were determined, along with the VD of the optic nerve head (ONH) in the radial peripapillary capillary (RPC) network. Additionally, cerebral MRI and cognitive function tests were performed. In the macula area, the VD of the CSVD patients was significantly lower than HCs in the temporal quadrant of SRCP. In the ONH area, CSVD patients had lower VD than HCs in the peripapillary RPC network. According to multiple linear regression analysis, decreased VD of the macular SRCP was associated with white matter hyperintensity scores after adjustment for age, hypertension, diabetes, and hyperlipidemia. Furthermore, the VD of the macular SRCP was significantly correlated with CSVD patients' cognitive function, especially global cognition, memory function, attention function, information processing, and executive function. OCTA revealed a significant decrease in retinal microvascular perfusion in CSVD patients, and retinal hypoperfusion was related to MRI markers and cognitive function, suggesting that these parameters could have potential utility as early disease biomarkers.

Gastric Bypass Improves Microvascular Perfusion in Patients with Obesity.

Basic science research has shown that obesity is associated with microvascular endothelial dysfunction. However, whether bariatric surgery impacts the microvascular networks has yet to be explored. This study sought to evaluate the impact of gastric bypass in the retinal microvasculature. Patients with obesity (BMI ≥ 35kg/m2) scheduled to gastric bypass were consecutively recruited and included in the study. Patients were evaluated before surgery and 6-12months after the intervention. Macular microvascular properties were evaluated using optical coherence tomography (OCT) angiography. Foveal avascular zone area, perimeter, circularity, and foveal and perifoveal vascular density (in both superficial and deep vascular plexus) were computed. In total, 40 eyes from 20 patients were included (30% male, mean BMI 43.4 ± 4.5kg/m2 (range 35.7-51.4). From these, 45% were diabetic before bariatric surgery. After surgery, there was a significant increase in foveal avascular zone circularity (from 0.85 ± 0.09 to 0.92 ± 0.07, p = 0.001) and vascular density in perifoveal deep vascular plexus (from 0.69 ± 0.12 to 0.73 ± 0.12; p = 0.04), whereas foveal avascular zone perimeter decreased (from 2.34 ± 0.37 to 2.20 ± 0.35mm, p = 0.007). Preoperative diabetic status was not a predictor of microvascular retinal changes after bariatric surgery. However, after multivariate adjustments, the increased drop in HbA1c after the surgery remained associated with the increase in perifoveal vascular density in the deep vascular plexus (B = 0.05; 95% CI 0.05-0.10; p = 0.03). Gastric bypass improves retinal microvascular perfusion as demonstrated by the increased parafoveal vascular density in the deep vascular plexus, increased foveal avascular zone circularity, and decreased foveal avascular zone perimeter.

Quantitative Analysis of Retinal Microvascular Perfusion and Novel Biomarkers of the Treatment Response in Diabetic Macular Edema.

Purpose We aimed to assess the changes of retinal microvascular parameters using optical coherence tomography angiography (OCTA) between diabetes macular edema (DME) and controls. We assessed the changes between the baseline microvascular parameters and final treatment response in patients with DME, initially treated with intravitreal dexamethasone (DEX) implant followed by antivascular endothelial growth factor (VEGF) injections on an as-needed basis. Methods This retrospective study included 90 DME patients and 24 healthy control subjects. All subjects had their best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured at baseline and after 12 months. Vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the deep/superficial flow ratio at baseline were analyzed. A subgroup analysis was used to compare the treatment response. A poor-response group was defined by five or more retreatments at 12 months. Results BCVA and CMT showed a significant improvement at 12 months (all p < 0.001). The VD in the whole and parafoveal areas of the DCP was significantly reduced in DME patients compared to that in controls (all p < 0.05). The DCP/SCP flow ratio was also significantly reduced in the DME group (1.08 ± 0.03 vs. 1.05 ± 0.02, p = 0.001). In the subgroup analysis, the VD in the foveal and whole DCP areas was significantly lower in the poor-response group than that in the good-response group (p = 0.043 and p = 0.048, respectively). The DCP/SCP flow ratio was also significantly lower in the poor-response group (p = 0.011). Conclusion DME correlated with significant retinal microvascular impairment in the DCP. A decreased DCP/SCP flow ratio was observed in patients with DME that exhibited a poor treatment response. Retinal microvascular parameters could predict the treatment response in DME and help optimize clinical outcomes.