Hypertension Likely Drives Arteriolar Wall Thickening in Preclinical Diabetic Retinopathy While Diabetes Drives Wall Thickness in Clinical Retinopathy.

Purpose: Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the timing and relative impact of hypertension versus diabetes on the WLR in diabetic retinopathy (DR) to address this unresolved question. Methods: This prospective cross-sectional study compared the retinal arteriolar WLR in 17 healthy eyes, 15 with diabetes but no apparent DR (DM no DR), and 8 with diabetic macular edema (DME) and either nonproliferative or proliferative DR. We imaged each arteriole using adaptive optics scanning laser ophthalmoscopy and measured the WLR using ImageJ. Multiple linear regression (MLR) was performed to estimate the effects of hypertension, diabetes, and age on the WLR. Results: Both subjects with DM no DR and subjects with DME had significantly higher WLR than healthy subjects (0.36 ± 0.08 and 0.42 ± 0.08 vs. 0.29 ± 0.07, 1-way ANOVA P = 0.0009). MLR in healthy subjects and subjects with DM no DR showed hypertension had the strongest effect (regression coefficient = 0.08, P = 0.009), whereas age and diabetes were not significantly correlated with WLR. MLR in all three groups together (healthy, DM no DR, and DME) showed diabetes had the strongest effect (regression coefficient = 0.05, P = 0.02), whereas age and hypertension were not significantly correlated with WLR. Conclusions: Hypertension may be an early driver of retinal arteriolar wall thickening in preclinical DR, independent of age or diabetes, whereas changes specific to DR may drive wall thickening in DME and later DR stages. Translational Relevance: We offer a framework for understanding the relative contributions of hypertension and diabetes on the vascular wall, and emphasize the importance of hypertension control early in diabetes even before DR onset.

Central retinal artery occlusion: a stroke of the eye.

Central retinal artery occlusion (CRAO), like a stroke in the brain, is a critical eye condition that requiring urgent medical attention. Patients with CRAO present with acute loss of vision and the visual prognosis is poor with low chance of spontaneous visual recovery. Moreover, the risk of developing ischaemic heart disease and cerebral stroke is increased due to the presence of underlying atherosclerotic risk factors. Currently, there is no officially recommended treatment for CRAO. This review will describe the anatomy, pathophysiology, clinical features of CRAO, as well as exploring existing and potential future approaches for managing the condition.

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.

Early remodeling and loss of light-induced dilation of retinal small arteries in CADASIL.

A major hurdle to therapeutic development in cerebral small vessel diseases is the lack of in-vivo method that can be used repeatedly for evaluating directly cerebral microvessels. We hypothesised that Adaptive Optics (AO), which allows resolution images up to 1-2 µm/pixel at retinal level, could provide a biomarker for monitoring vascular changes in CADASIL, a genetic form of such condition. In 98 patients and 35 healthy individuals, the wall to lumen ratio (WLR), outer and inner diameter, wall thickness and wall cross-sectional area were measured in a parapapillary and/or paramacular retinal artery. The ratio of vessel diameters before and after light flicker stimulations was also calculated to measure vasoreactivity (VR). Multivariate mixed-model analysis showed that WLR was increased and associated with a larger wall thickness and smaller internal diameter of retinal arteries in patients. The difference was maximal at the youngest age and gradually reduced with aging. Average VR in patients was less than half of that of controls since the youngest age. Any robust association was found with clinical or imaging manifestations of the disease. Thus, AO enables the detection of early functional or structural vascular alterations in CADASIL but with no obvious link to the clinical or imaging severity.

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.

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.

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.