Reversed Neurovascular Coupling on Optical Coherence Tomography Angiography Is the Earliest Detectable Abnormality before Clinical Diabetic Retinopathy

Diabetic retinopathy (DR) has traditionally been viewed as either a microvasculopathy or a neuropathy, though neurovascular coupling deficits have also been reported and could potentially be the earliest derangement in DR. To better understand neurovascular coupling in the diabetic retina, we investigated retinal hemodynamics by optical coherence tomography angiography (OCTA) in individuals with diabetes mellitus (DM) but without DR (DM no DR) and mild non-proliferative DR (mild NPDR) compared to healthy eyes. Using an experimental design to monitor the capillary responses during transition from dark adaptation to light, we examined 19 healthy, 14 DM no DR and 11 mild NPDR individuals. We found that the only structural vascular abnormality in the DM no DR group was increased superficial capillary plexus (SCP) vessel density (VD) compared to healthy eyes, while mild NPDR eyes showed significant vessel loss in the SCP at baseline. There was no significant difference in inner retinal thickness between the groups. During dark adaptation, the deep capillary plexus (DCP) VD was lower in mild NPDR individuals compared to the other two groups, which may leave the photoreceptors more susceptible to ischemia in the dark. When transitioning from dark to ambient light, both diabetic groups showed a qualitative reversal of VD trends in the SCP and middle capillary plexus (MCP), with significantly decreased SCP at 5 min and increased MCP VD at 50 s compared to healthy eyes, which may impede metabolic supply to the inner retina during light adaptation. Mild NPDR eyes also demonstrated DCP dilation at 50 s and 5 min and decreased adjusted flow index at 5 min in light. Our results show altered neurovascular responses in all three macular vascular plexuses in diabetic subjects in the absence of structural neuronal changes on high resolution imaging, suggesting that neurovascular uncoupling may be a key mechanism in the early pathogenesis of DR, well before the clinical appearance of vascular or neuronal loss.

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Analysis of Foveal Microvascular Abnormalities in Diabetic Retinopathy Using Optical Coherence Tomography Angiography with Projection Artifact Removal

Journal of Ophthalmology ◽

10.1155/2018/3926745 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Lun Liu ◽

Jian Gao ◽

Weili Bao ◽

Chengyang Hu ◽

Yajing Xu ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Optical Coherence Tomography Angiography ◽

Vessel Density ◽

Foveal Avascular Zone ◽

Optical Coherence ◽

Artifact Removal ◽

Significant Difference ◽

Patients With Diabetes ◽

Capillary Plexus

Purpose. To analyze foveal microvascular abnormalities in different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) with projection artifact removal (PAR). Methods. We analyzed 93 eyes of 59 patients with diabetes—31 with no DR (no DR), 34 with mild to moderate nonproliferative DR (mild DR), and 28 with severe nonproliferative DR to proliferative DR (severe DR)—and 31 age-matched healthy controls. Sections measuring 3 × 3 mm2 centered on the fovea were obtained using OCTA. The area, perimeter, and acircularity index (AI) of the foveal avascular zone (FAZ), vessel density within a 300 μm wide region of the FAZ (FD-300), and parafoveal vessel density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were calculated using novel built-in software with PAR. Results. There was no statistically significant difference in the FAZ area (p=0.162). There was a statistically significant difference in the FAZ perimeter (p=0.010) and the AI (p<0.001) between the four groups. There was a correlation between the AI and the increasing severity of DR (p=0.010). Statistically significant decreases of vessel density in the FD-300, SCP, and DCP were observed (all p<0.001). There was a difference in parafoveal vessel density in the DCP between the healthy control eyes and the eyes with diabetes without DR (p=0.027). There was a significant correlation between vessel density and increasing severity of DR (p<0.001). Conclusion. Compared with the FAZ area, AI allows a more helpful quantitative assessment of the changes in the FAZ. Vessel density determined using OCTA with PAR might be a useful parameter indicating the progression of DR. Parafoveal vessel density in the DCP after PAR might be a potential early biomarker of DR before appearance of clinically evident retinopathy and needs further investigation.

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Retinal microcirculation abnormalities in patients with systemic sclerosis: an explorative optical coherence tomography angiography study

Rheumatology ◽

10.1093/rheumatology/keab258 ◽

2021 ◽

Author(s):

Adriano Carnevali ◽

Giuseppe Giannaccare ◽

Valentina Gatti ◽

Caterina Battaglia ◽

Giorgio Randazzo ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Optical Coherence Tomography Angiography ◽

Flow Index ◽

Digital Ulcers ◽

Optical Coherence ◽

Vascular Abnormalities ◽

Capillary Plexus ◽

Retinal Microcirculation ◽

Vascular Plexuses

Abstract Objectives To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A). Methods A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries. Results The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients. Conclusion We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.

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Repeatability of ocular surface vessel density measurements with optical coherence tomography angiography

BMC Ophthalmology ◽

10.1186/s12886-019-1255-2 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Sijie Cai ◽

Fengping Zhao ◽

Chixin Du

Keyword(s):

Optical Coherence Tomography ◽

Ocular Surface ◽

Optical Coherence Tomography Angiography ◽

Imaging System ◽

Intraclass Correlation ◽

Vessel Density ◽

Optical Coherence ◽

Significant Difference ◽

Surface Vessel ◽

Healthy Eyes

Abstract Background To determine the repeatability of measurements of ocular surface vessel density in normal and diseased eyes using optical coherence tomography angiography (OCTA). Methods Ten normal eyes, 10 pinguecula eyes, and 10 pterygium eyes of 30 volunteers were subjected to OCTA (AngioVue Imaging System, Optovue, Inc.). For scanning, we used the corneal adapter module. Each eye was scanned three times in the nasal and temporal directions, separately. AngioVue software was used to generate the ocular surface vessel density. Ocular surface vessel density was defined as the proportion of vessel area with blood flow to the total measurement area (3 × 3 mm2). Intersession repeatability of the measurement was summarized as the coefficient of variation (CV), and intraclass correlation coefficients (ICC) were calculated by variance component models. Results The CVs were less than 5% in all subjects, and the ICCs exceeded 0.9; thus, all measurements showed good repeatability. The nasal vessels densities differed significantly between healthy eyes and eyes with pterygium (P < 0.05); however, there was no significant difference between healthy eyes and eyes with pinguecula (P = 0.466). Conclusions These results suggest that measurement of ocular surface vessel density by OCTA in normal eyes and eyes with pterygium and pinguecula is repeatable. This preliminary research describes a quantitative and visual method for assessing vessel density of the ocular surface with a high level of consistency.

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Optical coherence tomography angiography in diabetic patients without diabetic retinopathy

European Journal of Ophthalmology ◽

10.1177/1120672119895701 ◽

2019 ◽

Vol 30 (6) ◽

pp. 1418-1423 ◽

Cited By ~ 1

Author(s):

Claudio Furino ◽

Grazia Montrone ◽

Maria Vittoria Cicinelli ◽

Stefania Balestra ◽

Maria Oliva Grassi ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Optical Coherence Tomography Angiography ◽

Vessel Density ◽

Foveal Avascular Zone ◽

Diabetic Patients ◽

Optical Coherence ◽

Avascular Zone ◽

Capillary Plexus ◽

Superficial Capillary Plexus

Purpose: To investigate a subset of diabetic patients without diabetic retinopathy with optical coherence tomography angiography, assessing the differences in macular perfusion between diseased eyes and healthy controls. Methods: Monocentric cross-sectional study, including 86 eyes from 43 diabetic patients with no clinical signs of diabetic retinopathy and 78 eyes from 39 controls. Patients underwent 3.0 × 3.0 mm and 4.5 × 4.5 mm swept-source optical coherence tomography angiography. Vessel density (%), foveal avascular zone area (mm2), and avascular density (%) were provided for the superficial capillary plexus and the deep capillary plexus. Results: The foveal avascular zone area at the superficial capillary plexus was larger in the study group compared to controls, irrespective of the area of the slab considered. A meaningful difference was found in the vessel density at the deep capillary plexus of the 3.0 × 3.0 mm slab (p = 0.03). Almost all the variables considered in the study showed a significant within-subject effect. Age significantly correlated with vessel density of superficial capillary plexus on 4.5 × 4.5 mm in both control and diabetic eyes. Conclusion: Diabetic patients with subclinical diabetic retinopathy feature a larger foveal avascular zone at the superficial capillary plexus compared with controls, as well as relative reduction of the vessel density at the deep capillary plexus. These findings might serve as the basis for screening between normal and diabetic subjects.

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Evaluating Retinal and Choroidal Perfusion Changes After Ocular Massage of Healthy Eyes Using Optical Coherence Tomography Angiography

Medicina ◽

10.3390/medicina56120645 ◽

2020 ◽

Vol 56 (12) ◽

pp. 645

Author(s):

Felix Rommel ◽

Sabine Lüken ◽

Michelle Prasuhn ◽

Maximilian Kurz ◽

Vinodh Kakkassery ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Treatment Option ◽

Optical Coherence Tomography Angiography ◽

Retinal Artery Occlusion ◽

Artery Occlusion ◽

Optical Coherence ◽

Capillary Plexus ◽

Retinal Artery ◽

The Impact ◽

Healthy Eyes

Background and objectives: Ocular massage (OM) is used as a treatment option for acute retinal artery occlusion, under the assumption that it induces vessel dilatation and enhances perfusion. Since evidence of ocular perfusion alteration due to OM is lacking, we investigate the impact of OM on the hemodynamics of the posterior pole in healthy eyes in a noninvasive fashion by using optical coherence tomography angiography (OCTA). Materials and Methods: A prospective study was conducted on healthy volunteers, each of whom underwent measurements of intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), radial peripapillary capillary perfusion (RPCP), superficial capillary plexus perfusion (SCPP), deep capillary plexus perfusion (DCPP), choriocapillaris perfusion (CCP), Sattler’s layer perfusion (SLP) and Haller’s layer perfusion (HLP) before and after OM. OM was performed for 2 min, consisting of 10-s turns of compression and decompression of the globe. Results: A total of 21 eyes from 21 participants (median age 29) were included. After OM, IOP significantly declined (p < 0.001), while SFCT (p < 0.005), SCPP (p < 0.001), DCPP (p = 0.004) and CCP (p = 0.008) significantly increased. CMT, RPCP, SLP and HLP did not show any significant alteration due to OM. Changes in SCPP correlated positively with changes in CCP and vice versa. Conclusions: OCTA-based analysis in healthy adults following OM demonstrated a significant increase of retinal perfusion values, assumed to be due to failure of autoregulatory mechanisms. These findings may indicate a positive effect of OM as a treatment option for patients with acute retinal artery occlusion.

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Quantitative Evaluation of Vascular Density in Diabetic Retinopathy Subtypes using Optical Coherence Tomography Angiography

10.21203/rs.3.rs-63001/v1 ◽

2020 ◽

Author(s):

Fariba Ghassemi ◽

Kaveh Fadakar ◽

Sahar Berijani ◽

Ameneh Babeli ◽

Alireza Gholizadeh ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Optical Coherence Tomography Angiography ◽

Normal Subjects ◽

Vascular Density ◽

Diabetic Patients ◽

Multivariate Linear Regression Analysis ◽

Optical Coherence ◽

Potential Biomarker ◽

Capillary Plexus

Abstract Background: To determine the discrepancy between quantitative measurement of retinal and choriocapillaris (CC) vascular density (VD) in diabetic retinopathy (DR) stages using spectral domain optical coherence tomography angiography (SD OCTA) and compare it with normal subjects.Methods: 188 eyes of 97 participants were recruited in this cross-sectional study. Macular OCTA (3x3mm) scan was performed and VD at the level of superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC were measured with the device software.Results: In normal subjects, VD in SCP, DCP, and CC were higher in all subsegments. In retinal VD, all calculated parameters were reduced in the more extreme stages of DR, except for foveal VD of SCP. There was a constant pattern of decrease in VD of CC from normal cases to cases of NDR and NPDR and then a slight increase happened in the PDR stage but never touching the normal quantities. Age, fasting blood sugar, and years of diabetes mellitus were correlated with reduced VD in different segments. Multivariate linear regression analysis showed that best-corrected visual acuity (BCVA) was positively correlated with parafoveal VD at SCP and VD of foveal area at CC. VD of all subfields of macular area except foveal DCP VD showed reduced levels in diabetic macular edema (DME) patients compared to those without DME.Conclusions: The findings of the study endorse retina VD changes as a potential biomarker for DR development before retinopathy becomes clinically evident. It seems that parafoveal VD of SCP and foveal VD of CC are good biomarkers to predict VA in the diabetic patients.

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Quantitative assessment of choriocapillaris flow deficits in diabetic retinopathy: A swept-source optical coherence tomography angiography study

PLoS ONE ◽

10.1371/journal.pone.0243830 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243830

Author(s):

Yining Dai ◽

Hao Zhou ◽

Qinqin Zhang ◽

Zhongdi Chu ◽

Lisa C. Olmos de Koo ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Healthy Subjects ◽

Optical Coherence Tomography Angiography ◽

Optical Coherence ◽

Swept Source ◽

Significant Difference ◽

En Face ◽

The Mean

Purpose To quantitatively assess choriocapillaris (CC) flow deficits in eyes with diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA). Methods Diabetic subjects with different stages of DR and age-matched healthy subjects were recruited and imaged with SS-OCTA. The en face CC blood flow images were generated using previously published and validated algorithms. The percentage of CC flow deficits (FD%) and the mean CC flow deficit size were calculated in a 5-mm-diameter circle centered on the fovea from the 6×6-mm scans. Results Forty-five diabetic subjects and 27 control subjects were included in the study. The CC FD% in diabetic eyes was on average 1.4-fold greater than in control eyes (12.34±4.14% vs 8.82±2.61%, P < 0.001). The mean CC FD size in diabetic eyes was on average 1.4-fold larger than in control eyes (2151.3± 650.8μm2 vs 1574.4±255.0 μm2, P < 0.001). No significant difference in CC FD% or mean CC FD size was observed between eyes with nonproliferative DR and eyes with proliferative DR (P = 1.000 and P = 1.000, respectively). Conclusions CC perfusion in DR can be objectively and quantitatively assessed with FD% and FD size. In the macular region, both CC FD% and CC FD size are increased in eyes with DR. SS-OCTA provides new insights for the investigations of CC perfusion status in diabetes in vivo.

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Vascular Abnormalities in Peripapillary and Macular Regions of Behcet's Uveitis Patients Evaluated by Optical Coherence Tomography Angiography

Frontiers in Medicine ◽

10.3389/fmed.2021.727151 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chun Yan ◽

Fan Li ◽

Min Hou ◽

Xiaoyuan Ye ◽

Lishi Su ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Optical Coherence Tomography Angiography ◽

Vascular Density ◽

Optical Coherence ◽

Flow Area ◽

Vascular Abnormalities ◽

Behçet’S Uveitis ◽

Capillary Plexus ◽

Area And Perimeter ◽

Healthy Eyes

Purpose: To investigate the involvement of peripapillary zone vascular abnormalities in Behcet's uveitis (BU) and associated visual dysfunction. We evaluated the retinal and choroidal microvascular features in both macular and peripapillary areas of BU patients to identify vascular abnormalities contributing to reduced best-corrected visual acuity (BCVA) using optical coherence tomography angiography (OCTA).Methods: A prospective, observational study was conducted in 24 eyes of 13 patients with BU and 24 eyes of 15 healthy participants as controls. They received a standard eye examination and were recorded by OCTA measurements of macular and peripapillary areas. The vascular densities of superficial capillary plexus (SCP) and deep capillary plexus (DCP), choroidal flow area, radial peripapillary capillary network (RPCN) density, foveal avascular zone (FAZ) area and perimeter, full retinal thickness (FRT), and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured.Correlations among microvascular, structural, and functional changes were assessed.Results: Our findings uncovered that the vascular density was significantly reduced in the peripapillary zone of BU eyes compared to healthy eyes, especially in the inferior subfield of the RPCN. The vascular densities of SCP and DCP quadrants within the macular zone had no significant difference between BU and control groups except for DCP density of the nasal parafoveal quadrant. Both FAZ area and perimeter were greater but without statistical significance in the BU group. Compared to healthy eyes, the choriocapillaris flow area was smaller while the FRT and pRNFLT were greater in the BU group. Notably, there was a significant correlation between the reduction in RPCN vascular density and decreased BCVA in BU patients.Conclusion: Based on OCTA, vascular changes associated with BU are more prominent in the peripapillary zone than those in the macular zone. The vascular density of the RPCN could serve as a sensitive indicator to monitoring BU pathogenic progression and treatment response using a non-invasively method of OCTA.

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Evaluation of Radiation Maculopathy after Treatment of Choroidal Melanoma with Ruthenium-106 using Optical Coherence Tomography Angiography

10.21203/rs.3.rs-362423/v1 ◽

2021 ◽

Author(s):

Ali Torkashvand ◽

Hamid Riazi-Esfahani ◽

Fariba Ghassemi ◽

Elias Khalil Pour ◽

Babak Masoomian ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Optical Coherence Tomography Angiography ◽

Choroidal Melanoma ◽

Case Series ◽

Foveal Avascular Zone ◽

Optical Coherence ◽

Vascular Area ◽

Capillary Plexus ◽

The Impact ◽

Healthy Eyes

Abstract BACKGROUND: To assess the impact of brachytherapy on macular microvasculature utilizing optical coherence tomography angiography (OCTA) in treated choroidal melanoma.METHODS: In this retrospective observational case series, we reviewed the recorded data of the patients with choroidal melanoma treated with rheuthenium-106 (106Ru) plaque radiotherapy with follow-up period of more than 6 months. Automatically measured OCTA retinal parameters were analyzed after image processing. The non-irradiated fellow eye is considered as the control.RESULTS: Thirty-one eyes of 31 patients with the mean age of 51.1 years were recruited. Six eyes had no radiation maculopathy (RM). From 25 eyes with RM, nine eyes (36%) revealed a burnout macular microvasculature with imperceptible vascular details. Foveal and optic disc radiation dose had the highest value to predict the burnout pattern (ROC, AUC: 0.763, 0.727). Superficial and deep foveal avascular zone (FAZ) were larger in irradiated eyes in comparison to healthy eyes (1629 µm2 vs. 428 µm2, P =0.005; 1837 µm2 vs 268 µm2, P =0.021; respectively). Foveal and parafoveal vascular area density (VAD) and vascular skeleton density (VSD) in both superficial and deep capillary plexus (SCP and DCP) were decreased in all irradiated eyes in comparison with control eyes (P< 0.001). Compared with fellow healthy eyes, irradiated eyes without RM had significantly lower VAD and VSD at foveal and parafoveal DCP (all P<0.02). However, these differences at SCP were not statistically significant. CONCLUSION: The OCTA is a valuable tool for evaluating RM. Initial subclinical microvascular insult after 106Ru brachytherapy is more likely to occur in DCP. The deep FAZ area was identified as a more critical biomarker of BCVA than superficial FAZ in these patients.

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