Small Retinal Vessels Research Articles

Response of capillaries and small arterioles to full-field flicker is not dependent on local ganglion cell thickness

To measure the influence of ganglion cell layer (GCL) thickness on the changes in size and red blood cell (RBC) flow in small retinal vessels evoked by full-field flicker. We used a dual-beam adaptive optics scanning laser ophthalmoscope to image 11 healthy young controls in two retinal areas with significantly different GCL thicknesses. All capillaries and arterioles of the superficial vascular plexus were responsive to the flicker stimulation. Average lumen dilation and RBC flow changes were greater in capillaries than in arterioles (vasodilation: 10.9%, 6.7%; RBC flow: 51%, 38%, respectively). No statistically significant differences regarding relative lumen diameter, RBC velocity, or RBC flow were found with respect to GCL thickness, or vessel size.

The association between retinal vascular fractal dimension and cognitive function in the community-dwelling older adults cohort TIGER

The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df), representing the complexity of the retinal microcirculation. However, the connection between retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between retinal vascular complexity and cognitive impairment over time in non-demented community-dwelling older adults. This four-year prospective cohort study (2015-2019) is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research (TIGER, 2011 to present). Of the 434 older adults (age >65) recruited, 207 participants were included for analysis. The retinal vascular Df was assessed by baseline images from fundus photography (2015-2017). Global (Montreal Cognitive Assessment-Taiwanese version, MoCA-T) and domain-specific cognition were assessed at the baseline and 2-year follow-up (2017-2019). The multivariable linear regression models and generalized linear mixed models were used to evaluate the association of Df with cognitive decline/impairment over time. Decreased left retinal vascular complexity was associated with poor attention performance (β=-0.40). As follow-up time increased, decreased vascular complexity was associated with poor memory performance (right: β=-0.25; left: β=-0.19), and decreased right vascular complexity was associated with poor attention performance (β=-0.18). Low retinal vascular complexity of the right or left eye may be differentially associated with cognitive domains in community-dwelling older adults over two years. The retinal vascular Df of either eye may be served as a screening tool for detecting cognitive impairment in the preclinical phase of dementia.

Improved fully convolutional neuron networks on small retinal vessel segmentation using local phase as attention.

Retinal images have been proven significant in diagnosing multiple diseases such as diabetes, glaucoma, and hypertension. Retinal vessel segmentation is crucial for the quantitative analysis of retinal images. However, current methods mainly concentrate on the segmentation performance of overall retinal vessel structures. The small vessels do not receive enough attention due to their small percentage in the full retinal images. Small retinal vessels are much more sensitive to the blood circulation system and have great significance in the early diagnosis and warning of various diseases. This paper combined two unsupervised methods, local phase congruency (LPC) and orientation scores (OS), with a deep learning network based on the U-Net as attention. And we proposed the U-Net using local phase congruency and orientation scores (UN-LPCOS), which showed a remarkable ability to identify and segment small retinal vessels. A new metric called sensitivity on a small ship (Sesv ) was also proposed to evaluate the methods' performance on the small vessel segmentation. Our strategy was validated on both the DRIVE dataset and the data from Maastricht Study and achieved outstanding segmentation performance on both the overall vessel structure and small vessels.

Inception V3 and CNN Approach to Classify Diabetic Retinopathy Disease

Abstract: Diabetic retinopathy (DR) is one of the disease which is unobservable to the people and it is also an underlying disease that causes eye-related disorders due to collective damage to small retinal blood vessels. As a result both eyes can be affected leading to partial or complete vision loss. Diabetic Retinopathy is linked with uncontrollable sugar level or diabetic level. To prevent the initial damage and permanent blindness, its early detection must be followed. Whereas, there are automated diagnostic systems are implied in early detection and diagnosis of severe eye complications by providing helping hand to the ophthalmologists. The proposed research achieved improvements to enhance the performance in terms of accuracy, loss and speedy detection. In continuation with the same, the research has been done by implying Convolution Neural Network (CNN) along with Inception Version 3 (V3) model which yield accuracy of 99.35% with 0.02 loss. The proposed model makes it more accurate due to less epochs i.e., 10 epochs. The proposed model has been supported with Diabetic Retinopathy Detection 2015 and Aptos 2019 Blindness Detection and they both were received from Kaggle so to develop our reliable approach for identifying different Diabetic Retinopathy

Measuring Temporal and Spatial Variability of Red Blood Cell Velocity in Human Retinal Vessels.

PurposeThe retinal circulation regulates blood flow through various internal and external factors; however, it is unclear how locally these factors act within the retinal microcirculation. We measured the temporal and spatial variability of blood velocity in small retinal vessels using a dual-beam adaptive optics scanning laser ophthalmoscope.MethodsIn young healthy subjects (n = 3), temporal blood velocity variability was measured in a local vascular region consisting of an arteriole, capillary, and venule repeatedly over 2 days. Data consisted of 10 imaging periods separated into two sessions: (1) five 6-minute image acquisition periods with 30-minute breaks, and (2) five 6-minute image acquisition periods with 10-minute breaks. In another group of young healthy subjects (n = 5), spatial distribution of velocity variability was measured by imaging three capillary segments during three 2-minute conditions: (1) baseline imaging condition (no flicker), (2) full-field flicker, and (3) no flicker condition again.ResultsBlood velocities were measurable in all subjects with a reliability of about 2%. The coefficient of variation (CV) was used as an estimate of the physiological variability of each vessel. Over 2 days, the average CV in arterioles was 7% (±2%); in capillaries, it was 19% (±6%); and, in venules, it was 8% (±2%). During flicker stimulation, the average capillary CV was 16% during baseline, 15% during flicker stimulation, and 18% after flicker stimulation.ConclusionsCapillaries in the human retina exhibit spatial and temporal variations in blood velocity. This inherent variation in blood velocity places limits on studying the vascular regulation of individual capillaries, and the study presented here serves as a foundation for future endeavors.

Multichannel Retinal Blood Vessel Segmentation Based on the Combination of Matched Filter and U-Net Network.

Aiming at the current problem of insufficient extraction of small retinal blood vessels, we propose a retinal blood vessel segmentation algorithm that combines supervised learning and unsupervised learning algorithms. In this study, we use a multiscale matched filter with vessel enhancement capability and a U-Net model with a coding and decoding network structure. Three channels are used to extract vessel features separately, and finally, the segmentation results of the three channels are merged. The algorithm proposed in this paper has been verified and evaluated on the DRIVE, STARE, and CHASE_DB1 datasets. The experimental results show that the proposed algorithm can segment small blood vessels better than most other methods. We conclude that our algorithm has reached 0.8745, 0.8903, and 0.8916 on the three datasets in the sensitivity metric, respectively, which is nearly 0.1 higher than other existing methods.

Reduced Oxygen Extraction in the Retinal Periphery When the Arterial Blood Pressure Is Increased by Isometric Exercise in Normal Persons.

PurposeRecent evidence suggests that the smaller retinal vessels are significantly involved in the regulation of retinal blood flow and that this regulation may differ among the macular area and the retinal periphery. An alternative to studying blood flow regulation in smaller retinal vessels that are difficult to resolve is to assess the metabolic consequences of changes in the microcirculation using oximetry.MethodsIn 20 normal persons aged (mean ± SD, range) 30.1 ± 3.8 (24–37) years, the oxygen saturation and diameter of retinal arterioles and venules to the macular area and the retinal periphery were studied before and during an increase in the arterial blood pressure induced by isometric exercise.ResultsThe isometric exercise increased the mean arterial blood pressure by (mean ± SEM) 10.0 ± 1.1 mm Hg but induced no significant changes in the diameter of the arterioles (P = 0.83). The isometric exercise had no significant effect on the oxygen saturation in the arterioles supplying the macular area and the retinal periphery (P > 0.42 for both comparisons). However, there was a significant increase in the oxygen saturation in venules draining the retinal periphery to reduce the oxygen extraction from (mean ± SEM) 36.0% ± 2.3% to 30.6% ± 2.1% (P = 0.002) but no significant change in the preexisting low oxygen extraction in the macular area that changed from (mean ± SEM) 18.2% ± 3.0% to 16.2% ± 1.9% (P = 0.37).ConclusionsMinor changes in the arterial blood pressure can induce changes in retinal rheology with significant regional variation. The finding may help explain regional variations in manifestations of retinal vascular disease such as hyperpermeability in the macular area and capillary occlusion in the retinal periphery.

Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke

Objective: To explore the relationship between the total cerebral small vessel disease (CSVD) score and retinal vessel diameters in patients with mild stroke. Methods: The patients with mild stroke who were hospitalized in the Second People's Hospital of Changzhou, Nanjing Medical University from March to December 2019 were continuously collected (National Institutes of Health Stroke Scale score≤3 points). All patients completed the head magnetic resonance imaging and retinal fundus photography examination, and then the retinal arteriovenous diameter was measured semi-automatically based on the pictures. According to the total CSVD score (0-4 points), the patients were divided into 5 groups. The baseline characteristics of the patients were compared. Moreover, the correlation of total CSVD with retinal blood vessel diameters were analyzed by spearman and linear regression. Results: A total of 206 patients were enrolled. There were 69, 51, 41, 30, and 15 patients with 0, 1, 2, 3, and 4 points, respectively. In CSVD subgroups, there were significant differences in age, duration of hypertension and diabetes (all P<0.05). The central retinal artery equivalent (CRAE), (CSVD scores 0-4 were (126±12) μm, (118±11) μm, (108±11) μm, (99±8) μm, (90±7) μm, P<0.001) and arteriole-to-venule ratio (AVR) (CSVD scores 0-4 were 0.65±0.05, 0.60±0.04, 0.56±0.04, 0.49±0.03, 0.44±0.02, P<0.001) were different in CSVD subgroups. With the increase of CSVD score, the diameter of artery and AVR became smaller. The total CSVD was significantly correlated with AVR by Spearman correlation analysis (r= 0.818, P<0.001). By constructing a linear regression equation model, the coefficient of determination of the total CSVD score (R2=0.694) was higher than that of lacunes, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space. After adjusting for age, course of hypertension and diabetes, and different types of CSVD, further multiple linear regression analysis revealed that the total CSVD score was still an independent related factor of AVR (β=-0.039, P<0.001, 95%CI=-0.051--0.028). Conclusions: Total CSVD score is negatively correlated with retinal artery diameters and AVR. Additionally, the total CSVD score can better reflect the degree of cerebral microvascular lesions than single type CSVD.

The association between retinal vascular fractal dimension and cognitive function in the community‐dwelling elderly cohort TIGER

AbstractBackgroundCerebral vascular factor plays an important role in the pathogenesis of cognitive dysfunction, including mild cognitive impairment (MCI) and dementia. The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df) representing the complexity of the retinal microcirculation. However, the connection between the retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between the retinal vascular Df and cognitive dysfunction in the community‐dwelling older adults.MethodThis study is part of a prospective cohort Taiwan Initiative for Geriatric Epidemiological Research (TIGER, 2011 to present). Participants from the 4‐year (2015–2017) and 6‐year (2017‐2019) follow‐ups were included. Global and domain‐specific cognitive function were assessed at the 4‐year and 6‐year follow‐ups. Fundus photography was taken for each participant at the 4‐year follow‐up, and retinal vessels were segmented for fractal analyses. Multivariable logistic regression analyses were performed to explore the association between Df of the retinal vessels and cognitive decline over 2 years adjusting for age, gender, years of education, diabetes, hypertension, hyperlipidemia, cardiovascular event, smoking, drinking and age‐related macular degeneration.ResultHigher right retinal vascular complexity (right Df) was associated with the decline of logical memory‐recall I [linear right Df: adjusted odds ratio (aOR)= 0.30, 95% confidence interval (CI)= 0.11 to 0.85). No significant linear association was found between Df and global cognition or other cognitive domains. For non‐linear relationship, we found an inverted U shape association between the right Df and global cognitive decline over 2 years [quadratic right Df: aOR=0.10, 95% CI = 0.01‐0.80]. The risk of global cognitive decline (assessed by MoCA‐T) was 0.1 when right Df change 0.1 unit (increase or decrease) from the sample mean (1.36). Similar nonlinear relationship was found for the decline of logical memory‐recall II over 2 years (quadratic right Df: aOR= 0.08, 95% CI= 0.01‐0.59). No significant association was found between left Df and cognitive decline over 2 years.ConclusionThis study demonstrated a nonlinear relationship between the retinal vascular complexity of the right eye and the decline of global cognition and logical memory. This retinal biomarker may be used for screening dementia in the preclinical stage.

Diabetic retinopathy severity grading employing quadrant‐based Inception‐V3 convolution neural network architecture

AbstractDiabetic retinopathy (DR) accounts in eye‐related disorders due to accumulated damage to small retinal blood vessels. Automated diagnostic systems are effective in early detection and diagnosis of severe eye complications by assisting the ophthalmologists. Deep learning‐based techniques have emerged as an advancement over conventional techniques based on hand‐crafted features. The authors have proposed a Quadrant‐based automated DR grading system in this work using Inception‐V3 deep neural network to extract small lesions present in retinal fundus images. The grading efficiency of the proposed architecture is improved utilizing image enhancement and optical disc removal pipeline along with data augmentation stage. The proposed system yields accuracy of 93.33% with minimized cross‐entropy loss of 0.291. Capability of proposed system is demonstrated experimentally to provide efficient DR diagnosis. The diagnosis ability of the proposed architecture is demonstrated by state‐of‐the‐art comparison with other mainstream convolution neural network models and a maximum improvement of 14.33% is observed.

Full-field flicker evoked changes in parafoveal retinal blood flow

When retinal activity is increased by exposure to dynamic visual stimuli, blood vessels dilate and the flow of blood within vessels increases to meet the oxygen and glucose demands of the neurons. This relationship is termed ‘neurovascular coupling’ and it is critical for regulating control of the human retinal vasculature. In this study, we used a recently developed technique based on a dual-beam adaptive optics scanning laser ophthalmoscope to measure changes in red blood cell velocities, vessel diameter, and flow in interconnected small parafoveal retinal vessels (< 50 µm) of nine healthy participants. A full-field flicker stimulus was presented onto the retina to induce a vascular response to neural activity. Flicker stimulation increased blood velocity, vessel diameter, and therefore flow in arterioles, capillaries, and venules in all nine subjects. ANOVA and post hoc t-test showed significant increases in velocity and flow in arterioles and venules. These measurements indicate that the mechanism of neurovascular coupling systematically affects the vascular response in small retinal vessels in order to maintain hemodynamic regulation in the retina when exposed to visual stimulation, in our case flicker. Our findings may provide insight into future investigations on the impairments of neurovascular coupling from vascular diseases such as diabetic mellitus.

Relationship Between Venules and Perivascular Spaces in Sporadic Small Vessel Diseases.

Background and Purpose- Perivascular spaces (PVS) around venules may help drain interstitial fluid from the brain. We examined relationships between suspected venules and PVS visible on brain magnetic resonance imaging. Methods- We developed a visual venular quantification method to examine the spatial relationship between venules and PVS. We recruited patients with lacunar stroke or minor nondisabling ischemic stroke and performed brain magnetic resonance imaging and retinal imaging. We quantified venules on gradient echo or susceptibility-weighted imaging and PVS on T2-weighted magnetic resonance imaging in the centrum semiovale and then determined overlap between venules and PVS. We assessed associations between venular count and patient demographic characteristics, vascular risk factors, small vessel disease features, retinal vessels, and venous sinus pulsatility. Results- Among 67 patients (69% men, 69.0±9.8 years), only 4.6% (range, 0%-18%) of venules overlapped with PVS. Total venular count increased with total centrum semiovale PVS count in 55 patients after accounting for venule-PVS overlap (β=0.468 [95% CI, 0.187-0.750]) and transverse sinus pulsatility (β=0.547 [95% CI, 0.309-0.786]) and adjusting for age, sex, and systolic blood pressure. Conclusions- Despite increases in both visible PVS and suspected venules, we found minimal spatial overlap between them in patients with sporadic small vessel disease, suggesting that most magnetic resonance imaging-visible centrum semiovale PVS are periarteriolar rather than perivenular.

Multi-Label Classification Scheme Based on Local Regression for Retinal Vessel Segmentation.

Segmenting small retinal vessels with width less than 2 pixels in fundus images is a challenging task. In this paper, in order to effectively segment the vessels, especially the narrow parts, we propose a local regression scheme to enhance the narrow parts, along with a novel multi-label classification method based on this scheme. We consider five labels for blood vessels and background in particular: the center of big vessels, the edge of big vessels, the center as well as the edge of small vessels, the center of background, and the edge of background. We first determine the multi-label by the local de-regression model according to the vessel pattern from the ground truth images. Then, we train a convolutional neural network (CNN) for multi-label classification. Next, we perform a local regression method to transform the previous multi-label into binary label to better locate small vessels and generate an entire retinal vessel image. Our method is evaluated using two publicly available datasets and compared with several state-of-the-art studies. The experimental results have demonstrated the effectiveness of our method in segmenting retinal vessels.

Flicker evoked changes in small retinal vessels

Flicker evoked changes in small retinal vessels

Particle swarm optimization method for small retinal vessels detection on multiresolution fundus images

Retinal vessel segmentation plays an important role in the diagnosis of eye diseases and is considered as one of the most challenging tasks in computer-aided diagnosis (CAD) systems. The main goal of this study was to propose a method for blood-vessel segmentation that could deal with the problem of detecting vessels of varying diameters in high- and low-resolution fundus images. We proposed to use the particle swarm optimization (PSO) algorithm to improve the multiscale line detection (MSLD) method. The PSO algorithm was applied to find the best arrangement of scales in the MSLD method and to handle the problem of multiscale response recombination. The performance of the proposed method was evaluated on two low-resolution (DRIVE and STARE) and one high-resolution fundus (HRF) image datasets. The data include healthy (H) and diabetic retinopathy (DR) cases. The proposed approach improved the sensitivity rate against the MSLD by 4.7% for the DRIVE dataset and by 1.8% for the STARE dataset. For the high-resolution dataset, the proposed approach achieved 87.09% sensitivity rate, whereas the MSLD method achieves 82.58% sensitivity rate at the same specificity level. When only the smallest vessels were considered, the proposed approach improved the sensitivity rate by 11.02% and by 4.42% for the healthy and the diabetic cases, respectively. Integrating the proposed method in a comprehensive CAD system for DR screening would allow the reduction of false positives due to missed small vessels, misclassified as red lesions.

Using mathematics to avoid blindness in diabetics

Purpose: Avoid diabetic-blindness by applying five simple mathematically-inspired treatments that achieve life-long recovery from advanced diabetic retinopathy (ADR), without laser treatments or Avastin (Hoffmann-La Roche, Basel, Switzerland) injections.Methods: A mathematical model of ADR is derived; it is based on fluid leakage from abnormal ‘holes’ in small retinal blood vessels. First, the volume of a microscopic fluid droplet leaking from a single small vein-hole during a single heartbeat is derived from the Navier-Stokes flow-equations. Then, total fluid volume leaking into the retina from all M vein holes in N heartbeats is determined. Six parameters in the equations of the model with significant influence on leakage rates and leaked volumes are identified. These insights are used to design and then apply five simple, novel, and eff icient therapeutic treatments, T1 to T5, that may achieve recovery from ADR without laser surgery or Avastin injections. Daily rates, as well as total volumes, of macular fluid accumulation, removal (by eye-pumps), and leakage are calculated from optical coherence tomography (OCT)-measured macular thicknesses.Results: Ten years ago, this paper’s primary author, Arieh Helfgott (AH), suffered from ADR that no longer responded to laser surgery. After simultaneous application of treatments T1-T5, AH recovered from ADR in 42 days and has been free of ADR for over ten years, without needing Avastin injections. Leakage-volumes were shown to be very sensitive to small changes in hole diameters. In ADR, modest increases of 2.4%, 5.7%, 10.7%, 15%, and 19% in hole diameters induce impressive 10%, 25%, 50%, 75%, and 100% (volume-doubling) increases in leakage volumes, respectively. In recovery from ADR, modest decreases of −2.6%, −5.4%, −8.5%, −12%, and −15.9% in hole diameters induce equally impressive −10%, −20%, −30%, −40%, and −50% (volume-halving) decreases in leakage volumes, respectively.Conclusion: In AH’s case, mathematics helped in avoiding blindness from ADR. Simultaneous application of mathematics-inspired treatments T1-T5 resulted in reduced leakage from holes, elimination of retinal swelling (RS), and sustained recovery from ADR. With high sensitivity to hole diameters, advancing DR can easily become unmanageable, while recovery from ADR may possibly be achievable in approximately six weeks using efficient blood pressure (BP) control and small ‘repairs’ leading to reduction in hole diameters. The pumping rate of the eye is colossal; eye pumps can remove a macula-volume-equivalent in approximately 44 days. This is very helpful in recovery from ADR, and spectacular for such microscopic pumps

A multi-scale tensor voting approach for small retinal vessel segmentation in high resolution fundus images

Segmenting the retinal vessels from fundus images is a prerequisite for many CAD systems for the automatic detection of diabetic retinopathy lesions. So far, research efforts have concentrated mainly on the accurate localization of the large to medium diameter vessels. However, failure to detect the smallest vessels at the segmentation step can lead to false positive lesion detection counts in a subsequent lesion analysis stage. In this study, a new hybrid method for the segmentation of the smallest vessels is proposed. Line detection and perceptual organization techniques are combined in a multi-scale scheme. Small vessels are reconstructed from the perceptual-based approach via tracking and pixel painting.The segmentation was validated in a high resolution fundus image database including healthy and diabetic subjects using pixel-based as well as perceptual-based measures. The proposed method achieves 85.06% sensitivity rate, while the original multi-scale line detection method achieves 81.06% sensitivity rate for the corresponding images (p<0.05). The improvement in the sensitivity rate for the database is 6.47% when only the smallest vessels are considered (p<0.05). For the perceptual-based measure, the proposed method improves the detection of the vasculature by 7.8% against the original multi-scale line detection method (p<0.05).

A new model for studying diameter regulation of porcine retinal arterioles and capillaries in vitro

AbstractPurpose Studies of diameter regulation in retinal arterioles in vitro have mostly been performed on larger vessels, but evidence suggests that perturbations in the retinal microcirculation may also play a role in the development of vision threatening retinal diseases. Therefore, the purpose of the present study was to develop an in vitro technique for studying diameter regulation in both larger and smaller vessels.Methods A special tissue chamber was developed for mounting, cannulating and perfusing porcine hemiretinas while controlling temperature, pH and oxygen saturation. The chamber was mounted in a flourescens microscope, and the effect on the diameter of larger arterioles, pre‐capillary arterioles and capillaries was studied after intravascular and extravascular addition of the thromboxane analogue U46619 and lactate (n=6 for each variable) and NMDA (preliminary).Results In all vessel calibers the thromboxane analogue U46619 induced a significant contraction after extraluminal application (p&lt;0.02), but not after intraluminal (p&gt;0.13). Lactate had no effect on the diameter of non‐precontracted vessels (p&gt;0.21), but in pre‐contracted vessels lactate relaxed the vessel diameter.Conclusion The response to vasoactive compounds is different after intraluminal and extraluminal application, and the diameter response of vasoactive compounds is different in larger and smaller retinal vessels. The dilating effect of lactate depends on the state of contraction of the retinal vessel.

Retcam fluorescein angiography findings in eyes with advanced retinoblastoma

PurposeTo characterise the fluorescein angiogram (FA) findings of eyes with advanced retinoblastoma evaluated with the Retcam contact fundus camera.MethodsA retrospective case series was performed on all new retinoblastoma patients evaluated...

Morphogenetic Model for Radial Streaking in the Fundus of the Carrier State of X-Linked Albinism

Morphogenetic Model for Radial Streaking in the Fundus of the Carrier State of X-Linked Albinism