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Background: Hypertensive retinopathy (HR) is a retinal disease that may lead to vision loss and blindness. Sex-determining region Y (SRY)-box (SOX) family transcription factors have been reported to be involved in HR development. In this study, the role and upstream mechanism of SRY-box transcription factor 17 (SOX17) in HR pathogenesis were investigated., Methods: SOX17 and miR-194-5p levels in Angiotensin II (Ang II)-stimulated human retinal microvascular endothelial cells (HRMECs) and retinas of mice were detected by RT-qPCR. SOX17 protein level as well as levels of tight junction proteins and vascular endothelial growth factor (VEGF) signaling-associated proteins were quantified by western blotting. Tube formation assays were performed to evaluate angiogenesis in HRMECs. The structure of mouse retinal tissues was observed by H&E staining. The interaction between miR-194-5p and SOX17 was confirmed by a luciferase reporter assay., Results: SOX17 was upregulated in HRMECs treated with Ang II. SOX17 knockdown inhibited angiogenesis in Ang II-stimulated HRMECs and increased tight junction protein levels. Mechanically, SOX17 was targeted by miR-194-5p. Moreover, miR-194-5p upregulation restrained angiogenesis and increased tight junction protein levels in Ang II-treated HRMECs, and the effect was reversed by SOX17 overexpression. MiR-194-5p elevation inactivated VEGF signaling via targeting SOX17. miR-194-5p alleviated pathological symptoms of HR in Ang II-treated mice, and its expression was negatively correlated with SOX17 expression in the retinas of model mice., Conclusions: MiR-194-5p upregulation suppressed Ang II-stimulated HRMEC dysfunction and mitigates the symptoms of HR in mice by regulating the SOX17/VEGF signaling.

The number of patients with arterial hypertension is continually increasing. Hypertension can cause organ complications, called hypertension-mediated organ damage (HMOD). One example is hypertensive retinopathy, in which high blood pressure (BP) damages both the retinal microcirculation and the retinal nerve fiber layer (RNFL). This can result in progressive and painless vision deterioration in some groups of patients. Unlike anywhere else in the human body, the microvasculature of the retina can be observed in vivo, and the progression of changes can be closely monitored. The harmful effect of increased BP on the eye is not only limited to hypertensive retinopathy, but can also lead to an exacerbation of diabetic retinopathy (DR) and to an increase in intraocular pressure (IOP), and it can also trigger the formation of thromboembolic lesions. This review presents an update on the pathogenesis of hypertensive retinopathy and the use of adaptive optics (AO) combined with optical coherence tomography (OCT) to evaluate the retinal microvasculature. The latest progress and directions of research in the field of hypertensive retinopathy are also discussed.

Diabetes and hypertension are complex pathologies with increasing prevalence nowadays. Their interconnected pathways are frequently manifested in retinopathies. Severe retinal consequences and their tight connections as well as their possible treatments are particularly important to retinal research. In the present, work we induced diabetes with streptozotocin in spontaneously hypertensive rats and treated them either with PACAP or olaparib and alternatively with both agents. Morphological and immunohistochemical analyses were carried out to describe cell-specific changes during pathologies and after different treatments. Diabetes and hypertension caused massive structural and cellular changes especially when they were elicited together. Hypertension was crucial in the formation of ONL and OPL damage while diabetes caused significant differences in retinal thickness, OPL thickness and in the cell number of the GCL. In diabetes, double neuroprotective treatment ameliorated changes of calbindin-positive cells, rod bipolar cells and dopaminergic amacrine cells. Double treatment was curative in hypertensive diabetic rat retinas, especially in the case of rod bipolar and parvalbumin-positive cells compared to untreated or single-treated retinas. Our results highlighted the promising therapeutic benefits of olaparib and PACAP in these severe metabolic retinal disorders.

Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre measured by the models and by expert human graders showed high agreement, with overall intraclass correlation coefficients of between 0.82 and 0.95. The models performed comparably to or better than expert graders in associations between measurements of retinal-vessel calibre and CVD risk factors, including blood pressure, body-mass index, total cholesterol and glycated-haemoglobin levels. In retrospectively measured prospective datasets from a population-based study, baseline measurements performed by the deep-learning system were associated with incident CVD. Our findings motivate the development of clinically applicable explainable end-to-end deep-learning systems for the prediction of CVD on the basis of the features of retinal vessels in retinal photographs.

This study investigated functional alterations in the cerebral network of patients with hypertensive retinopathy (HR) by resting-state functional magnetic resonance imaging (rs-fMRI) and degree centrality (DC) methods. 31 patients with HR along with 31 healthy controls (HC) closely matched in gender and age were enrolled for the research. All participants were examined by rs-fMRI, and the DC method was applied to evaluate alterations in spontaneous cerebral activity between the 2 groups. We used the independent samples t test to evaluate demographic and general information differences between HR patients and HCs. The 2-sample t test was used to compare the DC values of different cerebral regions between the 2 groups. The accuracy of differential diagnostic HR was analyzed by receiver operating characteristic (ROC) curve method for rs-fMRI DC values changes. Pearson's correlation coefficient was applied to determine the correlation between differences in DC in specific cerebral areas and clinical manifestation. Results showed that DC values were higher in the left cerebellum posterior lobe (LCPL), left medial occipital gyrus (LMOG), and bilateral precuneus (BP) of HR patients compared to HCs. Mean DC values were lower in the right medial frontal gyrus/bilateral anterior cingulate cortex of HR patients. Anxiety and depression scores were positively correlated with DC values of LMOG and LCPL, respectively. Bilateral best-corrected visual acuity in HR patients was negatively correlated with the DC value of BP. Hence, changes in DC in specific cerebral areas of patients with HR reflect functional alterations that provide insight into the pathophysiologic mechanisms of HR.

Hypertension is a serious global health problem. Hypertensive retinopathy is generally considered to be a predictor of vascular disease elsewhere in the human body. In the past few decades, a variety of grading systems have been proposed for hypertensive retinopathy. However, these grading systems have some limitations. This study utilized optical coherence tomography angiography (OCTA) to investigate the morphological changes and macular retinal microvasculature in depth among 100 patients with hypertensive retinopathy and 66 healthy participants. Five main pathological changes were discovered in hypertensive retinopathy, as follows: focal capillary sparsity, scattered microangioma, focal macular arch ring defects, focal capillary disorder, and focal capillary nonperfusion at the levels of the superficial and deep vascular networks. In addition, we have found that the number of various pathological changes shows an increasing trend as hypertensive retinopathy progresses and may be related to renal damage. Finally, deep vessel density tended to decrease with progressive stages of hypertensive retinopathy and could be the best indicator to predict the risk of hypertensive retinopathy. Our study, therefore, proposes 3 stages of hypertensive retinopathy without macular edema according to the pathophysiology found by OCTA: stage 1 (only focal capillary sparsity), taking the place of KWB grade I; stage 2 (focal capillary sparsity and scattered microangioma), taking the place of KWB grade II; and stage 3 (focal capillary sparsity, scattered microangioma, focal capillary disorder, and nonperfusion), taking the place of KWB grade III. Hence, OCTA may be a potentially useful tool for evaluating the pathophysiology and staging of hypertensive retinopathy. Further longitudinal prospective studies are needed to confirm our findings.

Competing Interests: Competing interests: None declared.

Preeclampsia (PE) is a hypertensive complication of pregnancy. Its cause is still unknown and it could be a risk factor for future ophthalmic problems. Retinal vascular bed alterations have been described as a consequence of PE, suggesting a retinopathy. Factors related to angiogenesis and vascular permeability, such as vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) or components of the renin angiotensin aldosterone system (RAAS), prorrenin/renin receptor ((P)RR) and angiotensin II type I receptor (AT1R) have been located in the retina, participating in other retinopathies, but it is unknown if they could participate in PE. Our aim was to elucidate whether VEGF, PEDF, (P)RR and AT1R could be modified during PE and during hypertension induced in rats with a history of PE. We used female Wistar rats and subrrenal aortic coarctation to induce PE, and after delivery, we induced a second hit by Nω-nitro-L-arginine methyl ester (L-NAME) administration. We measured blood pressure, proteinuria and pups development. In both models, eye fundal exploration and immunoblot for VEGF, PEDF, (P)RR and AT1R were performed. We found that the development of hypertension occurred faster in previously PE rats than in normal animals. VEGF, PEDF, (P)RR and AT1R were increased in PE, but in L-NAME-induced hypertension only (P)RR and AT1R were altered. Eye fundal data indicated that PE induced a level I retinopathy, but L-NAME induced a faster and more severe retinopathy in previously PE animals compared to previously normal pregnancy rats. These results indicate that PE predisposes to development of a faster and more severe retinopathy after a second hit. They also suggest that VEGF and PEDF seem to participate only in PE retinopathy, but in both models, RAAS components seem to have a more critical participation., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.

Purpose: It has been suggested that arteriolar annuli localized in retinal arterioles regulate retinal blood flow acting as sphincters. Here, the morphology and protein expression profile of arteriolar annuli have been analyzed under physiologic conditions in the retina of wild-type, β-actin-Egfp, and Nestin-gfp transgenic mice. Additionally, to study the effect of hypertension, the KAP transgenic mouse has been used., Methods: Cellular architecture has been studied using digested whole mount retinas and transmission electron microscopy. The profile of protein expression has been analyzed on paraffin sections and whole mount retinas by immunofluorescence and histochemistry., Results: The ultrastructural analysis of arteriolar annuli showed a different cell population found between endothelial and muscle cells that matched most of the morphologic criteria established to define interstitial Cajal cells. The profile of protein expression of these vascular interstitial cells (VICs) was similar to that of interstitial Cajal cells and different from the endothelial and smooth muscle cells, because they expressed β-actin, nestin, and CD44, but they did not express CD31 and α-SMA or scarcely express F-actin. Furthermore, VICs share with pericytes the expression of NG2 and platelet-derived growth factor receptor beta (PDGFR-β). The high expression of Ano1 and high activity of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase observed in VICs was diminished during hypertensive retinopathy suggesting that these cells might play a role on the motility of arteriolar annuli and that this function is altered during hypertension., Conclusions: A novel type of VICs has been described in the arteriolar annuli of mouse retina. Remarkably, these cells undergo important molecular modifications during hypertensive retinopathy and might thus be a therapeutic target against this disease.

Hypertension and diabetes mellitus represent modifiable risk factors for vascular disease. They cause microvascular remodeling, and ultimately result in end-organ damage. Therefore, development of methods for noninvasive quantification of the effects of hypertension and diabetes mellitus on microvasculature is of paramount importance. The two goals of the study were: 1) to characterize the geometric complexity and inhomogeneity of retinal vasculature in hypertensive retinopathy (HR) and in proliferative diabetic retinopathy (PDR) by using box counting fractal dimension and lacunarity analysis, and 2) to determine if the combination of these two parameters can be used to describe differences in the vascular tree geometry between HR and PDR. The extended set of retinal images from the publicly available STARE database was manually segmented by our expert, validated, and made available for other researchers to use. The healthy retinal vascular network has a higher complexity (fractal dimension) compared to that in HR and in PDR. However, there is no difference in microvascular complexity between HR and PDR. The inhomogeneity of the retinal microvascular tree (lacunarity) was higher in PDR compared to HR. Lacunarity and fractal dimension together quantitatively characterize microvascular geometry in the retina with higher specificity than fractal analysis alone., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: Hypertensive Retinopathy (HR) is a retinal disease which happened due to consistent high blood pressure (hypertension). In this paper, an automated system is presented that detects the HR at various stages using arteriovenous ratio and papilledema signs through fundus retinal images., Methods: The proposed system consists of two modules i.e. vascular analysis for calculation of arteriovenous ratio and optic nerve head (ONH) region analysis for papilledema.  First module uses a set of hybrid features in Artery or Vein (A/V) classification using support vector machine (SVM) along with its radial basis function (RBF) kernel for arteriovenous ratio. In second module, proposed system performs analysis of ONH region for possible signs of papilledema. This stage utilizes different features along with SVM and RBF for classification of papilledema., Results: The first module of proposed method shows average accuracies of 95.10%, 95.64% and 98.09%for images of INSPIRE-AVR, VICAVR, and local dataset respectively. The second module of proposed method achieves average accuracies of 95.93% and 97.50% on STARE and local dataset respectively., Conclusions: The system finally utilizes results from both modules to grade HR with good results. The presented system is a novel step towards automated detection and grading of HR disease and can be used as clinical decision support system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The pathogenesis of visual dysfunction in stroke remains unclear. The objective of this study was to explore retinal damage in stroke spontaneously hypertensive rats (SHR) and evaluate the role of curcumin in the retinal injury after stroke. Mature male SHR were used as the animal model for hypertension and age-matched male Wistar-Kyoto (WKY) rats as the normotensive controls. The rat model of stroke was made by bilateral vertebral artery electrocoagulation combined with transient bilateral common carotid artery ligation. The animals were randomly divided into sham group, ischemia/reperfusion group, solvent control group, and curcumin treatment group. Each group was subdivided into 2 h, 6 h, 24 h, 72 h, and 7 day after reperfusion. Blood pressure was measured in SHR and WKY rats. Eye fundus was examined in living animals, and then, tissue specimens were collected for histologic examination, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, and immunohistochemistry. Retinopathy, induced by I/R, was more serious in rats with hypertension than that in normotensive rats (retinal thickness index, p = 0.004). The number of apoptosis in retinal capillary cells and neurons reduced significantly in the curcumin-treated groups. Curcumin treatment inhibited phosphorylated c-Jun N-terminal kinase (JNK) expression in SHR after retinal I/R injury. Thus, hypertension aggravated retinal I/R injury after stroke. Curcumin, a specific inhibitor of JNK, can prevent the development of hypertensive retinopathy after I/R injury by inhibiting apoptosis in retinal capillary cells and neurons.

Ischemic retinopathies (IRs), such as retinopathy of prematurity (ROP), diabetic retinopathy (DR), and (in many cases) age-related macular degeneration (AMD), are ocular disorders characterized by an initial phase of microvascular changes that results in ischemia, followed by a second phase of abnormal neovascularization that may culminate into retinal detachment and blindness. IRs are complex retinal conditions in which several factors play a key role during the development of the different pathological stages of the disease. Increasing evidence reveals that oxidative stress and inflammatory processes are important contributors to the pathogenesis of IRs. Despite the beneficial effects of the photocoagulation and anti-VEGF therapy during neovascularization phase, the need to identify novel targets to prevent initial phases of these ocular pathologies is still needed. In this review, we provide an update on the involvement of oxidative stress and inflammation in the progression of IRs and address some therapeutic interventions by using antioxidants and anti-inflammatory agents.

The period of forming of superficial vascular plexus during physiological retinal angiogenesis was shorter in C57Bl/6 mice. Experiments on the model of oxygen-induced retinopathy showed that avascular and vascularized zones in BALB/c mice on day 17 are smaller than in C57Bl/6 mice are by 5 and 1.5 times, respectively. The obtained results confirmed the importance of phenotype of retinal macrophages in the regulation of processes of both physiological and pathological retinal angiogenesis.

To investigate the mechanism underlying AT1-AA-induced retinopathy in severe preeclampsia by measuring the positive rate and titer of AT1-AA in plasma from women with severe preeclampsia and normal pregnant women to see whether AT1-AA titer was correlated with the grade of retinopathy. A preeclampsia rat model was also established by intravenous injection of AT1-AA extracted from the plasma of patient suffering from severe preeclampsia. The results showed that the plasma titer and positive rate of AT1-AA were significantly higher in women with severe preeclampsia than normal pregnant women. The antibody titer in cases of severe preeclampsia was associated with the grade of retinopathy, and positively correlated with the level of TNF-α and VEGF. The animal experiment results showed that the modeled rats presented symptoms very similar to symptoms of human preeclampsia, including retinopathy. Ocular fundus examination showed retinal microvascular abnormalities, hemorrhaging and leakage in the severe preeclampsia. Morphological changes included edema, thickening of the INL and ONL, and pigment atrophy. TNF-α and VEGF levels were increased in the vitreous humor and retina of the model rats. Our studies results suggest that abnormal expression of AT1-AA could induce damage to retinal capillary endothelial cells and increase vascular permeability, resulting in retinopathy.

Background and Aims: Retinopathy and vascular calcification (VC) are representative markers of microvascular and macrovascular dysfunction in patients with chronic kidney disease (CKD). However, their relationship and combined effects on clinical outcomes remain undetermined., Methods and Results: We included 523 patients with nondialysis-dependent CKD stage 3-5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. Simple radiographs were analyzed for the presence of VC. The clinical significance of VC of the abdominal aorta and iliofemoral artery (apVC) and retinopathy was evaluated in terms of the rate of renal function decline and composite of any cardiovascular event or death. CKD patients with retinopathy showed higher prevalence of apVC than those without retinopathy (25.6% vs. 12.5%, P < 0.001).The presence of retinopathy was independently associated with apVC (OR 2.13, 95% CI 1.31, 3.49). In multivariate analysis, compared with subjects with neither apVC nor retinopathy, the coexistence of both apVC and retinopathy were independently associated with rapid renal function decline (β = -1.51; 95% CI -2.40, -0.61), whereas apVC or retinopathy alone were not. Compared with subjects with neither apVC nor retinopathy, the HRs for composite end points were 1.05 (95% CI 0.48, 2.27), 1.79 (95% CI 1.14, 2.80), and 2.07 (95% CI 1.17, 3.67) for patients with apVC only, those with retinopathy only, and those with both apVC and retinopathy, respectively., Conclusion: The coexistence of VC and retinopathy was independently associated with CKD progression and cardiovascular events or deaths, and its combined effect was stronger than any separate condition., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Posterior reversible encephalopathy syndrome (PRES) is a serious and increasingly recognized disorder in humans. However, isolated cerebellar involvement in PRES is extremely uncommon. In this study, we sought to investigate its clinical and radiological features by describing a cohort of cases with PRES and isolated cerebellar involvement., Methods: We report 2 patients with PRES with only cerebellar involvement and identified additional 9 cases using the PubMed database with the MeSH terms "posterior reversible encephalopathy syndrome", "hypertensive encephalopathy", "hypertension", "cerebellum", "encephalopathy", and "magnetic resonance imaging". We then collectively analyzed the clinical and imaging characteristics of these 11 cases., Results: The average age was 28years, with 8 male and 3 female patients. All cases had severe acute hypertension and T2 hyperintensity on MRI exclusively centered within the cerebellum. Of 11 patients, 7 had hypertensive retinopathy, a favorable clinical course with only antihypertensive treatment, and resolution of the cerebellar lesions on follow-up imaging. A total of 5 of the 11 patients received external ventricular drainage due to obstructive hydrocephalus and only 2 of the 11 had a seizure., Conclusions: Isolated cerebellar involvement in PRES may be a unique variant that affects younger, male cases with severe acute hypertension and hypertensive retinopathy, but not necessarily seizure. Most patients have full recovery after fast control of blood pressure. Awareness of atypical neuroimaging features in PRES is critical for appropriate treatment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The prevalence of childhood obesity is increasing worldwide. Studies in adult populations show that retinal microvascular changes are associated with obesity and components of the metabolic syndrome. In our study we have assessed the effect of body mass index (BMI), metabolic parameters, and adiposity on the retinal microvasculature in children., Methods: Fifty-four consecutive children with biopsy-proven NAFLD were enrolled in this study. Anthropometric and laboratory parameters were obtained using standardized protocols. Retinal caliber was quantified from digital retinal images using well-known computer-based programs. Twenty-four-hour ambulatory blood pressure monitoring was measured using a standard protocol., Results: In our population, the prevalence of retinopathy was of 53 % (13 males). The 29 patients with retinopathy (mean age 10.91 ± 3.10) showed significantly higher values of triglycerides (mg/day) (105.57 vs. 90.20, p = 0.04), basal insulin (mUI/ml) (17.20 vs. 12.97, p = 0.02), and HOMA-IR (3.37 vs. 2.76, p = 0.04). The patients with a HOMA-IR >2.5 (OR = 3.34, p = 0.02; 95 % IC, 1.07-10.39), and systolic non-dipping (OR 4.16, p = 0.028, 95 % IC, 1.11-13.67), have an increased risk of retinopathy. Moreover, the study of correlation between all stages of liver biopsy (CRN criteria) and the grade of retinopathy showed a positive correlation with fibrosis (r = 0.31) and an NAS score (r = 0.28)., Conclusions: We found an association between metabolic parameters and nocturnal blood pressure on the retinal microvasculature among the obese children with NAFLD. Furthermore, for the first time, we report the positive relationship between hepatic fibrosis in pediatric NAFLD patients and the degree of retinopathy signs.

Morphological analysis of the retinal vessels by fundoscopy provides noninvasive means for detecting and staging systemic microvascular damage. However, full exploitation of fundoscopy in clinical settings is limited by paucity of quantitative, objective information obtainable through the observer-driven evaluations currently employed in routine practice. Here, we report on the development of a semiautomated, computer-based method to assess retinal vessel morphology. The method allows simultaneous and operator-independent quantitative assessment of arteriole-to-venule ratio, tortuosity index, and mean fractal dimension. The method was implemented in two conditions known for being associated with retinal vessel changes: hypertensive retinopathy and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). The results showed that our approach is effective in detecting and quantifying the retinal vessel abnormalities. Arteriole-to-venule ratio, tortuosity index, and mean fractal dimension were altered in the subjects with hypertensive retinopathy or CADASIL with respect to age- and gender-matched controls. The interrater reliability was excellent for all the three indices (intraclass correlation coefficient ≥ 85%). The method represents simple and highly reproducible means for discriminating pathological conditions characterized by morphological changes of retinal vessels. The advantages of our method include simultaneous and operator-independent assessment of different parameters and improved reliability of the measurements.

Background/aims: Individuals who reach end-stage kidney disease (CKD5) have a high risk of vascular events that persists even after renal transplantation. This study compared the prevalence and severity of microvascular disease in transplant recipients and patients with CKD5., Methods: Individuals with a renal transplant or CKD5 were recruited consecutively from renal clinics, and underwent bilateral retinal photography (Canon CR5-45, Canon). Their retinal images were deidentified and reviewed for hypertensive/microvascular signs by an ophthalmologist and a trained grader (Wong and Mitchell classification), and for vessel caliber at a grading centre using a computer-assisted method and Knudtson's modification of the Parr-Hubbard formula., Results: Ninety-two transplant recipients (median duration 6.4 years, range 0.8 to 28.8) and 70 subjects with CKD5 were studied. Transplant recipients were younger (p<0.001), with a higher eGFR (p< 0.001), but were just as likely to have a moderate-severe hypertensive/microvascular retinopathy (46/92, 50%) as subjects with CKD5 (38/70, 54%; OR 0.84, CI 0.45 to 1.57, p=0.64), and had similar mean arteriole and venular calibres (135.1 ± 7.5 µm and 137.9 ± 14.9 µm, p=0.12; and 199.1 ± 17.8 µm and 202.4 ± 27.8 µm, p=0.36, respectively). Arteriole and venular caliber were not different in nine patients examined before and after transplantation (p=0.62 and p=0.11, respectively)., Conclusions: Hypertensive/microvascular disease occurred just as often and was generally as severe in transplant recipients and subjects with CKD5. Microvascular disease potentially contributes to increased cardiac events post-transplantation., (© 2015 S. Karger AG, Basel.)

Background: A 34-year-old western lowland gorilla presented with peracute blindness., Methods: Clinical evaluation, diagnostic imaging, laboratory analyses, blood pressure measurements, and necropsy were performed., Results: The clinical and postmortem findings supported malignant hypertension., Conclusions: We describe a case of naturally occurring hypertensive encephalopathy and retinopathy in a gorilla., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To identify the relationship of retinal arteries in a population with systemic arterial hypertension., Methods: High resolution, dilated, digitised, fundus photographs of consecutive patients with a history of hypertension requiring pharmacologic therapy seen on the Wills Eye Hospital Retina Service were analysed. Included were photographs of the temporal retinal vascular arcades in which media clarity permitted good visualisation of third-order retinal vascular bifurcations. Each first- and second-order arteriovenous (AV) crossing was then examined to identify anatomic patterns at the sites where veins and arteries crossed. Eyes in patients without a history of hypertension were used as controls., Results: Among the 71 patients (134 eyes), there were 430 first-order and second-order AV crossings, in which AV nicking was present at 126 sites. A retinal artery was located anterior to the retinal vein in 122 of the 126 sites (96.8%) at which AV nicking was noted, while nicking associated with the vein located anteriorly to the artery occurred in only 4 of 126 (3.2%) of AV crossings (p<0.001). An anatomical pattern of venous arching, or cascading of a retinal vein over a retinal artery, was noted predominantly when the vein was positioned anterior to the artery in both subjects and controls. Among the 43 venous arching sites in the study group, 41 (95.3%) demonstrated the retinal vein anterior to retinal artery (p<0.001)., Conclusions: In patients with systemic arterial hypertension and hypertensive retinopathy, AV nicking of the retinal vein at the site of AV crossing is seen predominantly when the retinal artery lies anterior to the vein, but generally not when the vein lies anterior to the artery. The clinician should realise that when a retinal vein lies anterior to a retinal artery, the absence of AV nicking does not rule out more severe, chronic, retinopathic changes than observed with retinal arterial straightening only.

Vascular retinopathy is the consequence of vascular disease, and the retina is the only place where the arteries can be visualized directly. The purpose of this study was to evaluate the predictive value of retinal vascular findings for carotid artery atherosclerosis. From December 2009 to January 2011, the carotid intima-media thickness (IMT) and total plaque area (TPA) were measured in 179 consecutive patients, who received a fundoscopic examination. The patients were divided into groups as follows: normal retinal artery (normal; n = 44), diabetic retinopathy (DR; n = 25), retinal artery occlusion (RAO; n = 17), retinal vein occlusion (RVO; n = 67), and hypertensive retinopathy (HTN-R; n = 26). The subjects were classified according to the presence of an increased (≥ 1 mm) IMT and plaque. The values of the mean carotid IMT in the patients with vascular retinopathy (DR, 0.87 ± 0.14 mm; RAO, 1.18 ± 0.47 mm; RVO, 0.84 ± 0.14 mm; HTN-R, 0.90 ± 0.20 mm) were significantly increased compared with those in the normal subjects (0.77 ± 0.13 mm). A total 77 of 135 vascular retinopathy patients demonstrated an increased IMT (57 %), and 97 vascular retinopathy patients had carotid artery plaque (72 %). The relative risk of vascular retinopathy in the prediction of an increased IMT and the presence of plaque was 2.79 and 3.95, respectively. Although The TPA was significantly increased in the patients with RAO (1.87 ± 2.67 cm(2)) and RVO (0.27 ± 0.23 cm(2)) compared with the normal subjects (0.18 ± 0.23 cm(2), all Ps < 0.05), there was no significant difference in the ipsilateral carotid IMT and TPA of the affected eye compared with that of the contralateral eye. In conclusion, vascular retinopathy demonstrated a good predictive value in identifying asymptomatic carotid artery atherosclerosis, and this was not confined to the ipsilateral carotid artery of the affected eye. Further recommendations with regard to carotid atherosclerosis screening in patients with vascular retinopathy should be considered.

Objective: Retinopathy and retinal microvascular abnormalities are common in adult populations, yet few long-term predictors have been identified. We therefore examined the association between systolic blood pressure (SBP) and fasting plasma glucose, assessed over 18 years, with retinopathy and retinal vascular caliber in 2066 Carotid MRI participants, an Atherosclerosis Risk in Communities ancillary study., Methods: Retinopathy and retinal vascular caliber were assessed by retinal photography. Confounder-adjusted weighted regression models were used to examine exposures defined as cumulative, long-term prospective, concurrent, and 18-year change., Results: Long-term prospective (prevalence odds ratio (POR) per 10 mm Hg: 1.14 (95% CI: 1.01, 1.30)) and cumulative (POR per 10 mm Hg: 1.30 (95% CI: 1.09, 1.56) effects spanning approximately 18 years were found for SBP and retinopathy. The strongest long-term prospective association for plasma glucose and retinopathy was identified at the baseline visit (POR per 10 mg/dl: 1.26 (95% CI: 1.16, 1.38)); sustained glucose elevations over 18 years were also associated with prevalent retinopathy (POR per 10 mg/dl: 1.33 (95% CI: 1.24, 1.43)). Results were robust to the exclusion of participants with diabetes., Conclusions: Modest and sustained long-term elevations in glucose and blood pressure are associated with retinopathy and retinal vascular caliber., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Mean platelet volume (MPV) has been recognized as an independent risk factor of hypertension. Hypertensive end-organ damage worsens the prognosis in hypertensive patients. We aimed to investigate the relationship between MPV levels and subclinical end-organ damage in hypertensive patients. One hundred and sixteen hypertensive patients (81 women, 35 men, with a mean age of 53 ± 11) were included in the study. There was no correlation between MPV and left-ventricular mass index (LVMI) (r = 0.145; P = 0.14) or albuminuria (r = 0.009; P = 0.93). Among the individuals that had grade I and grade II retinopathy, MPV levels (8.3 ± 2 fL, 8.2 ± 1.3 fL; P = 0.28) were similar either. We concluded that there was no correlation between MPV and markers of end-organ damage in hypertensive patients.

A decreased ratio of the width of retinal arteries to veins [arteriolar-to-venular diameter ratio (AVR)], is well established as predictive of cerebral atrophy, stroke and other cardiovascular events in adults. Tortuous and dilated arteries and veins, as well as decreased AVR are also markers for plus disease in retinopathy of prematurity. This work presents an automated method to estimate the AVR in retinal color images by detecting the location of the optic disc, determining an appropriate region of interest (ROI), classifying vessels as arteries or veins, estimating vessel widths, and calculating the AVR. After vessel segmentation and vessel width determination, the optic disc is located and the system eliminates all vessels outside the AVR measurement ROI. A skeletonization operation is applied to the remaining vessels after which vessel crossings and bifurcation points are removed, leaving a set of vessel segments consisting of only vessel centerline pixels. Features are extracted from each centerline pixel in order to assign these a soft label indicating the likelihood that the pixel is part of a vein. As all centerline pixels in a connected vessel segment should be the same type, the median soft label is assigned to each centerline pixel in the segment. Next, artery vein pairs are matched using an iterative algorithm, and the widths of the vessels are used to calculate the AVR. We trained and tested the algorithm on a set of 65 high resolution digital color fundus photographs using a reference standard that indicates for each major vessel in the image whether it is an artery or vein. We compared the AVR values produced by our system with those determined by a semi-automated reference system. We obtained a mean unsigned error of 0.06 (SD 0.04) in 40 images with a mean AVR of 0.67. A second observer using the semi-automated system obtained the same mean unsigned error of 0.06 (SD 0.05) on the set of images with a mean AVR of 0.66. The testing data and reference standard used in this study has been made publicly available.

Scheie's classification regarding hypertensive and atherosclerotic lesions in retinal arteries is generally used to assess the severity of hypertensive retinopathy and the risks of cardiovascular events in hypertensive patients. However, the differences between these two types of retinal artery lesions have not been fully examined. Both arterial stiffness and aortic root diameter are increased in hypertensive patients. The aim of this study was to elucidate differences in the two types of lesions by comparing their relationships to arterial stiffness and aortic root diameter in hypertensive patients following stroke. Fifty-two hypertensive patients following stroke were divided into five stages according to Scheie's classification of hypertensive (H stage 0-4) and atherosclerotic (S stage 0-4) lesions by ophthalmologists. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV) using an automatic waveform analyzer. Aortic root diameter was measured using M-mode echocardiography. The H and S stages in retinal arteries correlated with each other (ρ = 0.443, p < 0.001). However, the S stage correlated with baPWV (ρ = 0.385, p = 0.005) and the aortic root diameter (ρ = 0.285, p = 0.043), while the H stage did not correlate with these parameters. Multiple stepwise regression analysis demonstrated that the aortic root diameter was independently associated with S stage (β = 0.373, p = 0.006), even though baPWV was independently associated with neither S stage nor H stage. In conclusion, hypertensive lesions (H stage) in retinal arteries are associated with atherosclerotic lesions (S stage) in retinal arteries. However, S stage may reflect arterial stiffening and aortic root dilatation better than H stage in hypertensive patients following stroke. This difference between H and S stages of Scheie's classification should be kept in mind when considering the association between retinal microcirculation and large vessel arteriosclerosis.

The changes in diameter of retinal vessels are an important sign of diseases such as hypertension, arteriosclerosis and diabetes. Obtaining precise measurements of vascular widths is a critical and demanding process in automated retinal image analysis. This paper presents the development of a prototype for measuring the vessel diameters to calculate the arteriovenous ratio (AVR) by using different techniques including Gabor wavelet, gradients, morphological operations and Niblack. The diameter measurement is based on the image skeleton and the perpendicular segment of the vessel. An executable tool is developed using MATLAB and the results are evaluated.