Retinal vessel caliber and cognitive performance: the multi-ethnic study of atherosclerosis (MESA).

Retinal vessel calibers share anatomic and physiologic characteristics with the cerebral vasculature and can be visualized noninvasively. In light of the known microvascular contributions to brain health and cognitive function, we aimed to determine if, in a community based-study, retinal vessel calibers and change in caliber over 8 years are associated with cognitive function or trajectory. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort who completed cognitive testing at Exam 5 (2010-2012) and had retinal vascular caliber measurements (Central Retinal Artery and Vein Equivalents; CRAE and CRVE) at Exam 2 (2002-2004) and Exam 5 were included. Using multivariable linear regression, we evaluated the association of CRAE and CRVE from Exam 2 and Exam 5 and their change between the two exams with scores on tests of global cognitive function (Cognitive Abilities Screening Instrument; CASI), processing speed (Digit Symbol Coding; DSC) and working memory (Digit Span; DS) at Exam 5 and with subsequent change in cognitive scores between Exam 5 and Exam 6 (2016-2018).The main effects are reported as the difference in cognitive test score per SD increment in retinal vascular caliber with 95% confidence intervals (CI). A total of 4334 participants (aged 61.6 ± 9.2 years; 53% female; 41% White) completed cognitive testing and at least one retinal assessment. On multivariable analysis, a 1 SD larger CRAE at exam 5 was associated with a lower concomitant CASI score (- 0.24, 95% CI - 0.46, - 0.02). A 1 SD larger CRVE at exam 2 was associated with a lower subsequent CASI score (- 0.23, 95%CI - 0.45, - 0.01). A 1 SD larger CRVE at exam 2 or 5 was associated with a lower DSC score [(- 0.56, 95% CI - 1.02, - 0.09) and - 0.55 (95% CI - 1.03, - 0.07) respectively]. The magnitude of the associations was relatively small (2.8-3.1% of SD). No significant associations were found between retinal vessel calibers at Exam 2 and 5 with the subsequent score trajectory of cognitive tests performance over an average of 6 years. Wider retinal venular caliber was associated with concomitant and future measures of slower processing speed but not with later cognitive trajectory. Future studies should evaluate the utility of these measures in risk stratification models from a clinical perspective as well as for screening on a population level.

The value of quantitative contrast-enhanced ultrasonography analysis in evaluating central retinal artery microcirculation in patients with diabetes mellitus: comparison with colour Doppler imaging.

AIM: To compare the efficacy of quantitative contrast-enhanced ultrasonography (CEUS) analysis and colour Doppler ultrasound (CDU) in evaluating central retinal artery (CRA) microcirculation in patients with diabetes mellitus (DM). MATERIALS AND METHODS: In this prospective study, a total of 55 patients (98 eyes) with DM were enrolled as the study group. They were compared to 46 age-matched healthy volunteers (92 eyes) who were selected as the control group. Each patient underwent CDU and subsequent CEUS examination. CDU and quantitative CEUS parameters were evaluated. The diagnostic efficiency of the diagnostic performance of CEUS and CDU was evaluated and compared, and the scale thresholds of predictive indicators for the diagnosis of proliferative diabetic retinopathy (PDR) were evaluated using receiver operating characteristics (ROC) curve analyses. RESULTS: Group pairwise comparisons showed that the end diastolic velocity (EDV) and arrival time (AT) of CRA were significant predictors for PDR by CDU and by quantitative CEUS analysis, respectively (all p<0.05). The ROC curve analysis showed that the area under the curve value of AT was significantly higher than that of EDV (0.875 versus 0.634, p=0.0002). Accordingly, an AT cut-off value of 1.07 seconds resulted a sensitivity of 90.62 % and a specificity of 79.31 %. CONCLUSION: Quantitative CEUS analysis can improve the accuracy of clinical staging of diabetic retinopathy for the patients with DM, and the AT showed the best diagnostic efficiency.

Investigation of alterations in retrobulbar hemodynamics and their correlation with choroidal thickness after strabismus surgery.

BACKGROUND: To evaluate the changes in retrobulbar circulation after strabismus surgery and to assess the relationship of these changes with choroidal thickness (CT). METHODS: This prospective study included 26 eyes of 26 patients who underwent strabismus surgery and 15 eyes of 15 healthy individuals as control group. The patients who had single horizontal muscle surgery were included in Group 1 (n = 14); and those who had surgery on both horizontal muscles were included in Group 2 (n = 12). Peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) of ophthalmic artery (OA), posterior ciliary artery (PCA), and central retinal artery (CRA) were measured using Color Doppler Ultrasonography. Subfoveal CT was measured via Optical Coherence Tomography. All measurements were obtained preoperatively, at 1st week and 1st month after surgery. RESULTS: There were no differences regarding preoperative blood flow velocity parameters among the groups. OA RI increased significantly at 1st week and 1st month after surgery in Group 1 and 2 (P = 0.029 and P = 0.045, respectively). There was a significant increase in PCA PSV at 1st week in Group 1 (P = 0.002). There was no difference between the mean preoperative and postoperative CT among the 3 groups. A negative correlation between the percentage changes of CT and CRA EDV was found in Group 2 (P = 0.011). CONCLUSION: Single and double horizontal rectus muscle surgery have a measurable effect on retrobulbar hemodynamics but these changes do not correlate with CT.

Retinal artery to vein ratio is associated with cerebral microbleeds in individuals with type 1 diabetes.

OBJECTIVES: A third of asymptomatic individuals with type 1 diabetes (T1D) show signs of cerebrovascular disease in brain MRI. These signs associate with advanced stages of diabetic retinal disease, but not in mild or moderate retinopathy. We aimed to evaluate a wider spectrum of retinal changes by exploring the relationship between quantitative measures of retinal vessel parameters (RVP) and cerebrovascular changes in T1D. METHODS: We included 146 neurologically asymptomatic individuals with T1D [51% women, median age 40 (33.0-45.1) years] and 24 healthy, sex-matched and age-matched controls. All individuals underwent a clinical and biochemical work-up and brain MRI, which was evaluated for cerebral microbleeds (CMBs), white matter hyperintensities, and lacunar infarcts. RVPs, including central retinal arteriole (CRAE) and central retinal vein (CRVE) equivalents and the ratio of the two variables (arteriovenous ratio, AVR) were assessed quantitatively by a computer-assisted method (IVAN software, version 3.2.6) from fundus images. RESULTS: Among T1D participants, those with CMBs had a lower arteriovenous ratio (AVR) compared with those without CMBs ( P  = 0.023). AVR was inversely associated with the amount of CMBs ( r  = -0.063, P  = 0.035). CMB prevalence was higher in those with AVR below the median (31%) compared with above the median (16%, P  < 0.001), and this difference was significant also after individuals with only no-to-mild retinopathy were included (28 vs. 16%, P  = 0.005). A correlation between blood pressure and CRAE ( r  = -0.19, P  = 0.025) appeared among those with T1D. CONCLUSION: Regardless of the severity of diabetic retinopathy, AVR is associated with the existence of CMBs in T1D.

Multimodal imaging of congenital peri-papillary arterial loops presenting with vitreous hemorrage in a young male: A case report.

INTRODUCTION: Congenital arterial peripapillary loops are rare entities and very few cases are described in literature. CASE DESCRIPTION: A 25-year-old Asian man presented a diffuse vitreous hemorrhage in his Left Eye (LE). OCT-A revealed the presence of bilateral vascular loops at the optic nerve head. Fluorescein angiography (FA) confirmed the vascular abnormality in both eyes, with arterial filling in early phases and no dye leakage. At twenty days of follow up, the vitreous hemorrhage in the LE completely reabsorbed and BCVA improved from 20/63 to 20/20. CONCLUSION: Congenital peripapillary loops should be considered in the differential diagnosis of vitreous hemorrhage, especially in young patients with no history of ocular/head trauma. Multimodal imaging is highly recommended to properly manage the patients, avoiding unnecessary therapeutic choices.

The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro.

PURPOSE: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. METHODS: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. RESULTS: Bradykinin, VIP and CGRP induced significant concentration-dependent dilatation and NPY significant concentration-dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L-NAME reduced bradykinin- and VIP-induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. CONCLUSION: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Semi-supervised point consistency network for retinal artery/vein classification.

Recent deep learning methods with convolutional neural networks (CNNs) have boosted advance prosperity of medical image analysis and expedited the automatic retinal artery/vein (A/V) classification. However, it is challenging for these CNN-based approaches in two aspects: (1) specific tubular structures and subtle variations in appearance, contrast, and geometry, which tend to be ignored in CNNs with network layer increasing; (2) limited well-labeled data for supervised segmentation of retinal vessels, which may hinder the effectiveness of deep learning methods. To address these issues, we propose a novel semi-supervised point consistency network (SPC-Net) for retinal A/V classification. SPC-Net consists of an A/V classification (AVC) module and a multi-class point consistency (MPC) module. The AVC module adopts an encoder-decoder segmentation network to generate the prediction probability map of A/V for supervised learning. The MPC module introduces point set representations to adaptively generate point set classification maps of the arteriovenous skeleton, which enjoys its prediction flexibility and consistency (i.e. point consistency) to effectively alleviate arteriovenous confusion. In addition, we propose a consistency regularization between the predicted A/V classification probability maps and point set representations maps for unlabeled data to explore the inherent segmentation perturbation of the point consistency, reducing the need for annotated data. We validate our method on two typical public datasets (DRIVE, HRF) and a private dataset (TR280) with different resolutions. Extensive qualitative and quantitative experimental results demonstrate the effectiveness of our proposed method for supervised and semi-supervised learning.

Pregnancy induces retinal microvascular changes indicating cardio-metabolic stress.

We performed longitudinal examinations of the arterial retinal microvasculature using Adaptive Optics Retinal Imaging in a 30-year-old healthy woman with twin pregnancy from the 23rd week of gestation (wog) to three days postpartum. Two blinded graders recorded the average wall-to-lumen ratio (WLR) of the examined retinal artery. There was a significant increase in the mean WLR over the course of pregnancy followed by a decreasing WLR from the 37th wog. The demonstrated changes in WLR may be an expression of vascular remodeling and adaptation to volume load which indicates that pregnancy can be viewed as a cardiovascular stress test.

Retinal venular vessel diameters are smaller during ten days of bed rest.

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m-2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

Narrowing Ratio of Retinal Veins at Arteriovenous Crossing in Patients With Branch Retinal Vein Occlusion Versus That in Healthy Individuals.

Purpose: This cross-sectional study aimed to clarify the differences in the retinal venous narrowing ratio (VNR) at retinal arteriovenous crossing by optical coherence tomography (OCT) among the eyes with branch retinal vein occlusion (BRVO), fellow eyes of patients with BRVO, and eyes of individuals without BRVO and to determine factors that influence the VNR. Methods: We studied 31 eyes of young participants, 54 eyes of an older control group, 56 fellow eyes of patients with BRVO, and 48 eyes with BRVO. Cross-sectional OCT images were used to determine the VNR at two arteriovenous crossings per eye. Results: Overall, 378 arteriovenous crossings were analyzed. The VNR of arterial overcrossings of fellow eyes (27.7% ± 11.1%) and BRVO eyes (27.3% ± 9.76%) were significantly higher than those in the young (16.0% ± 7.9%, all P < 0.001) and control (22.0% ± 8.81%, P < 0.001, P = 0.003, respectively) groups. The VNR of arterial overcrossings was significantly larger than that of venous overcrossings (24.0% ± 10.5% vs. 20.6% ± 13.0%, P = 0.021). A linear mixed-effects model showed that the VNR was significantly higher in arterial overcrossings, crossings with larger arterial internal diameters, smaller venous internal diameters, and participants with older age and a BRVO history. Conclusions: The VNR in arterial overcrossings was higher in BRVO eyes and even in the fellow eyes. Thus, a higher VNR in arterial overcrossings may contribute to BRVO development, and crossings with factors contributing to higher VNR might be associated with a risk of BRVO.

Delineation of the central retinal artery using computed tomography: a pilot study.

PURPOSE: The prospective study aimed to examine the central retinal artery (CRA) using computed tomography (CT). MATERIALS AND METHODS: Seventy adult outpatients comprising 32 men and 38 women, at a mean age of 60.6 ± 13.3 years, were enrolled in the study. The patients underwent contrast-enhanced CT. The scan timing was set to start 5.0 s after the circle of Willis began to be delineated. RESULTS: The ophthalmic arteries (OphAs) were comfortably delineated in all. In 97% of the patients, the CRA was delineated from the original site on the OphA to a more distal segment coursing on the optic sheath. Unilateral and bilateral CRA delineations were observed in 44% and 53% of cases, respectively. The delineated CRAs demonstrated highly variable morphologies in terms of the course and length on the optic sheath. In addition, the distance between the original site of the CRA and the posterior limit of the bulb was measured. The mean distance was 18.6 ± 5.0 mm on the right and 17.8 ± 4.3 mm on the left, respectively. No significant right-to-left differences in the measurements (p > 0.05) were observed. CONCLUSIONS: If optimal scan timing is adopted, the CRA segments coursing on the optic sheath can be delineated using contrast-enhanced CT. CT may be a useful diagnostic modality for the CRAs and associated pathological conditions.

Association between resistivity index of central retinal artery and severity of diabetic retinopathy.

Purpose: Diabetic retinopathy (DR) is a leading cause of ocular morbidity. Its progression depends mainly on retinal vasculature and ocular blood flow. Color Doppler imaging (CDI) is a noninvasive imaging technique that measures blood flow velocity. The resistivity index (RI), calculated by the CDI, reflects the vascular resistance distal to the measuring location. RI is independent of the doppler angle and position of the patient, making it a reliable and reproducible parameter. To the best of our knowledge, there is only one study in literature studying the association between resistivity index (RI) of the central retinal artery (CRA) and severity of DR. Aim: To determine the association between RI of CRA and severity of DR. To determine the association between RI of CRA and spectral-domain optical coherence tomography (SD-OCT) biomarkers for DR. Methods: Type II diabetics visiting our OPD underwent DR screening and were graded into three categories according to ETDRS classification which include Group A-No diabetic retinopathy (No DR), Group B-Nonproliferative diabetic retinopathy (Moderate-Severe-Very Severe NPDR), and Group C-Proliferative diabetic retinopathy (PDR). SD-OCT was performed. Ultrasonic color doppler imaging was done. RI of the CRA was noted. It was compared between the three groups and its association with severity of DR and OCT biomarkers (central subfield thickness, cube average thickness and ellipsoid zone disruption) was studied. Results: 56 eyes of 28 patients were included in our study with 20 in Group A,14 in Group B, and 22 in Group C. RI of CRA compared within groups showed statistically significant association with severity of DR (P < 0.001). The presenting BCVA (LogMar) showed positive correlation with RI in all groups. OCT biomarker central subfield thickness showed a positive correlation with RI in Groups A (P < 0.001) and B. Ellipsoid zone (EZ) disruption showed a statistically significant association with RI in Group C (P < 0.001). Conclusion: The RI of CRA is a reliable biomarker for the assessment of the severity of DR. Patients with high RI of CRA had higher chances of EZ disruption and presented with poor visual acuity.