Retinal Microvascular Alterations Research Articles

Review of paediatric retinal microvascular changes as a predictor of cardiovascular disease.

Recent studies have supported the hypothesis that exposure to established cardiovascular risk factors in early life predisposes to the development of adult cardiovascular disease. Retinal imaging is an emerging technique which facilitates non-invasive, accurate and reproducible assessment of the retinal microvasculature. The assessment may be in the form of static vascular calibre measurements and assessment of the vascular geometry or dynamic structural and functional assessments. Paediatric retinal microvascular changes are reported in response to elevated blood pressure, type 1 diabetes, increasing adiposity, diet, physical activity, systemic inflammation, metabolic peptides, family history and prenatal factors. The resultant microvascular changes have been linked to sub-clinical and overt cardiovascular, cerebrovascular and metabolic disease states in the adult population. Still missing however is longitudinal evidence showing the persistence of retinal microvascular alterations into adulthood. Future studies will enable retinal microvascular assessment to further evaluate the pathogenesis of disease states and response to intervention. The data obtained will also aid in expanding the clinical utility of retinal imaging as a cardiovascular risk prediction and monitoring tool and supplement existing recommendations to reduce cardiovascular morbidity and mortality.

Effects of longitudinal body mass index variability on microvasculature over 5 years in adult Chinese

To explore the associations of 5-year trend and fluctuation in body mass index (BMI) with retinal vascular caliber in a middle-aged and elderly Chinese population. Participants age ≥40 years were recruited in a prospective study. Baseline BMI data were collected in 2008, and the participants were re-examined annually until 2012. Retinal vascular caliber was measured from fundus photographs collected in 2012. BMI trend was calculated as the slope of BMI against the time of examinations. BMI fluctuation was defined as the root mean square error around the regression line of BMI over time (BMI RMSE) and the coefficient of variation of BMI (BMI CV). Rising BMI trend was associated with narrower retinal arteriolar and wider venular calibers in the overall subjects, especially among persons with overweight and obesity (BMI ≥ 25 kg/m(2) , P = 0.004 and 0.033, respectively). Rising BMI trend was also significantly associated with narrower retinal arteriole even in nonobese individuals with BMI < 25 kg/m(2) (P = 0.017) when eliminating the effects of hypertension and diabetes. Neither BMI RMSE nor BMI CV was statistically associated with retinal vascular caliber (all P > 0.05). Annual rising trending BMI was associated with retinal microvascular alteration. The results suggest that weight gain probably increases the risk of cardiovascular diseases among middle-aged and elderly people.

Association of body composition and blood pressure categories with retinal vessel diameters in primary school children.

Alterations in retinal vessel diameters have been shown to be predictive of cardiovascular risk in adults and children. The aim of our study was to examine the association of body composition and blood pressure (BP) categories with retinal vessel diameters in school children. We examined anthropometric parameters, BP and retinal arteriolar (CRAE) and venular (CRVE) diameters as well as the arteriolar-to-venular diameter ratio (AVR) in 391 children (age: 7.3, s.d. 0.4). Differences between the lowest and highest BP quartiles indicated that higher systolic and diastolic BP were associated with narrower CRAE (P<0.001 for both). Children in the highest weight quartile had narrower CRAE compared with the lowest quartile (P=0.05). In the regression analysis, systolic and diastolic BP were associated with arteriolar narrowing (-0.4 measuring units (mu) per mm Hg, 95% confidence interval: [-0.6; -0.3] and -0.6 mu per mm Hg [-0.7; -0.4], respectively; P<0.001 for both). An independent association was found for diastolic BP only. Compared with normotensives (NT; 74.4% of cohort), arteriolar narrowing was already seen in children categorized as pre-hypertensive (PHT) (11.5% of cohort), which was similar to HT children (14.1% of cohort) (NT: mean 207.2 [205.6; 208.7] mu; PHT: 201.7 [197.8; 205.7] mu; HT: 199.7 [196.2; 203.3] mu; P=0.01 for PHT vs. NT and P<0.001 for HT vs. NT in systolic BP). Our results suggest that systolic and diastolic BP are main determinants of retinal arteriolar diameters; and therefore, microvascular health in young children. Pre-hypertension seems to be associated with retinal microvascular alterations early in life.

Cerebral white matter lesions and microcirculation retinal in stroke lacunar

Background: The blood vessels in the retina are available for viewing in a noninvasive way and have similar anatomical, physiological as features small vessel brain. Also the white matter lesions (WMLs) brain are most frequently associated with lacunar stroke Objective: To determine the relationship between cerebral white matter lesions and retinal microvascular alteration in lacunar stroke. Material and methods: Cross-sectional study, patients with acute stroke was evaluated. Arteriovenous crossings, focal or diffuse arteriolar narrowing, retinal hemorrhages, cotton wool spots, alteration in vascular path, microaneurysms, the presence of retinal microvascular abnormalities was assessed. The WMLs were evaluated with a ranking of 1 to 9. Lacunar Stroke was classified by the score of TOAST. Results: A total of 67 patients were evaluated, classified as lacunar stroke 23.88% (n:16), the average age was 70.06 years, 50% were men, the main risk factors hypertension 68.75%, hypercholesterolemia 50%, diabetes 31.25%. In reference to the degree of WMLs grade 4-9 was superior to no lacunar stroke with 68.75% vs. 56.86%, the presence of retinopathy was also higher in lacunar stroke with 68.75% vs. 52.94%, but we found the presence of retinopathy in patients without diabetes and hypertension. Conclusion: WMLs and altering of retinal microcirculation are more prevalence in patients with lacunar stroke. Likewise, the retinopathy may be present in these patients despite not having recognized cardiovascular risk factors.

Measurement of retinal wall-to-lumen ratio by adaptive optics retinal camera: a clinical research.

To measure the wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera. Forty-seven human subjects were examined and their medical history was explored. WLR and WCSA were measured on the basis of retinal arteriolar wall thickness (VW), lumen diameter (LD) and vessel diameter (VD) assessed by rtx1 Adaptive Optics retinal camera. WLR was calculated by the formula [Formula: see text]. Arterio-venous ratio (AVR) and microvascular abnormalities were attained by quantitative and qualitative assessment of fundus photographs. Influence of age, arterial hypertension, body mass index (BMI) and retinal microvascular abnormalities on the WLR was examined. An age-adjusted WLR was created to test influences on WLR independently of age. Considering WLR and WCSA, a distinction between eutrophic and hypertrophic retinal remodeling processes was possible. The intra-observer variability (IOV) was 6 % ± 0.9 for arteriolar wall thickness and 2 % ± 0.2 for arteriolar wall thickness plus vessel lumen. WLR depended significantly on the wall thickness (r = 0.715; p < 0.01) of retinal arterioles, but was independent of the total vessel diameter (r = 0.052; p = 0.728). WLR correlated significantly with age (r = 0.769; p < 0.01). Arterial hypertension and a higher BMI were significantly associated with an increased age-adjusted WLR. WLR correlated significantly with the stage of microvascular abnormalities. 55 % of the hypertensive subjects and 11 % of the normotensive subjects showed eutrophic remodeling, while hypertrophic remodeling was not detectable. WLR correlated inversely with AVR. AVR was independent of the arteriolar wall thickness, age and arterial hypertension. The technique of AO retinal imaging allows a direct measurement of the retinal vessel wall and lumen diameter with good intra-observer variability. Age, arterial hypertension and an elevated BMI level are significantly associated with an increased WLR. The wall-to-lumen ratio measured by AO can be used to detect structural retinal microvascular alterations in an early stage of remodeling processes.

Retinal microvascular abnormalities overlying choroidal nodules in neurofibromatosis type 1.

BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disorder involving aberrant proliferation of multiple tissues of neural crest origin. Retinal vascular alterations in NF1 have rarely been reported in the literature and their nature is not clear. This study describes distinctive retinal microvascular alterations and their relationship to choroidal nodules in patients with neurofibromatosis type 1.MethodsThis was a retrospective study where records of seventeen consecutive patients with diagnosis of NF1, presenting Lisch nodules and choroidal alterations, and 17 age and gender-matched healthy control patients were evaluated. Fundus photographs, near infrared reflectance and enhanced depth imaging - optical coherence tomography images were reviewed. Retinal microvascular abnormalities and choroidal and retinal alterations in proximity of the retinal microvacular alterations were carefully noted.Results6 patients (35%) presented distinctive microvascular abnormalities. These consisted of small, tortuous vessels with a “spiral” or “corckscrew” aspect. They were second or third order, small tributaries of the superior or inferior temporal vein. These vessels were all located overlying choroidal alterations as observed with near infrared reflectance. Enhanced depth imaging - optical coherence tomography showed alteration of choroidal vasculature due to the presence of choroidal nodules but otherwise retinal and choroidal cross-sections were unremarkable for morphology.ConclusionsRetinal microvascular alterations overlying choroidal nodules in patients with NF1 can be considered another distinctive characteristic of the disease. Although the nature of these alterations is not clear, the authors speculate that functional disorders of vasomotor nerve cells, which originate in the embryonal neural crest can lead to their formation.

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy.

In patients with diabetes mellitus (DM), early retinal microvascular alterations can be observed even before the clinical diagnosis of diabetic retinopathy. This study aimed to investigate morphological and functional changes in retinal microvascular blood flow in type 1 diabetic patients with and without peripheral neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with flicker light. PNP was assessed using the neuropathy disability score (NDS) and by the evaluation of the vibration perception threshold (VPT). A total of 41 subjects were recruited for study participation and were stratified to 3 different groups according to their metabolic and neurological status: 14 nondiabetic subjects without PNP, 14 diabetic patients without PNP, and 13 diabetic patients with PNP. All subjects were free from diabetic retinopathy as assessed by fundoscopy. In diabetic patients with PNP, baseline and stimulated RBF was higher compared with diabetic patients without PNP and the nondiabetic control group. No difference with regard to RBF could be observed between the nondiabetic control subjects and patients with type 1 DM without PNP. No difference in the arterial WLR could be observed between the 3 groups. A linear correlation was found for VPT and RBF (r = .38, P < .001) and for NDS and RBF (r = .44, P < .0001). In our study population of patients with type 1 diabetes, PNP was associated with functional but not morphological changes in RBF.

Assessment of Retinal Vasculature in Pregnancy: Unveiling the Complex Pathogenesis of Gestational Vascular Complications

Lupton et al1 get our applause for their innovative study on retinal microvascular alterations and subsequent development of preeclampsia. Changes in retinal calibers are not only overt in the early stages of essential hypertension as shown previously by our group2 but are now for the first time implicated in the multifaceted hypertensive disorder of preeclampsia. However, data on blood pressure (BP) levels and unadjusted for BP retinal calibers are not provided by the authors. Although normotensive until 20 weeks of gestation, women who subsequently develop preeclampsia may lack the BP drop normally observed during first weeks of pregnancy and exhibit prehypertensive BP levels. Indeed, normal but higher BP levels …

Could donor multipotent mesenchymal stromal cells prevent or delay the onset of diabetic retinopathy?

Diabetes mellitus is a complex metabolic disease that has become a global epidemic with more than 285 million cases worldwide. Major medical advances over the past decades have substantially improved its management, extending patients' survival. The latter is accompanied by an increased risk of developing chronic macro- and microvascular complications. Amongst them, diabetic retinopathy (DR) is the most common and frightening. Furthermore, during the past two decades, it has become the leading cause of visual loss. Irrespective of the type of diabetes, DR follows a well-known clinical and temporal course characterized by pericytes and neuronal cell loss, formation of acellular-occluded capillaries, occasional microaneurysms, increased leucostasis and thickening of the vascular basement membrane. These alterations progressively affect the integrity of retinal microvessels, leading to the breakdown of the blood-retinal barrier, widespread haemorrhage and neovascularization. Finally, tractional retinal detachment occurs leading to blindness. Nowadays, there is growing evidence that local inflammation and oxidative stress play pivotal roles in the pathogenesis of DR. Both processes have been associated with pericytes and neuronal degeneration observed early during DR progression. They may also be linked to sustained retinal vasculature damage that results in abnormal neovascularization. Currently, DR therapeutic options depend on highly invasive surgical procedures performed only at advanced stages of the disease, and which have proved to be ineffective to restore visual acuity. Therefore, the availability of less invasive and more effective strategies aimed to prevent or delay the onset of DR is highly desirable. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), are promising healing agents as they contribute to tissue regeneration by pleiotropic mechanisms, with no evidence of significant adverse events. Here, we revise the pathophysiology of DR to identify therapeutic targets for donor MSCs. Also, we discuss whether an MSC-based therapy could prevent or delay the onset of DR.

Structural Alterations of the Retinal Microcirculation in the “Prehypertensive” High- Normal Blood Pressure State

The high-normal blood pressure (also known as prehypertension) is a clinical condition characterized by an increased cardiovascular risk as well as by the presence of target organ damage. This include an increased left ventricular mass, an endothelial dysfunction and an early renal functional and structural damage. Whether this is the case also for alterations of retinal vessels network, which are frequently detectable in established hypertension, is still largey undefined. The present paper, after discussing the main characteristics of the high-normal blood pressure state, will review the different approaches used throughout the years for assessing retinal microcirculatory network. Data collected by our group in subjects with high normal blood pressure will be also discussed, showing that arterial venular ratio values are reduced in this individuals with high-normal blood pressure and more so in established hypertension. These data indicate that retinal microvascular alterations 1) are of early appearance in the clinical course of hypertension and 2) are of frequent detection in the high-normal blood pressure state. The possible hemodynamic and non-hemodynamic mechanisms resposible for these structural alteations of the retinal microcirculation will be also discussed.

Microvascular Complications and Diabetic Retinopathy: Recent Advances and Future Implications

Retinal microvascular alterations have been observed during diabetic retinopathy (DR) due to the retinal susceptibility towards subtle pathological alterations. Therefore, retinal microvascular pathology is essential to understand the nature of retinal degenerations during DR. In this review, the role of retinal microvasculature complications during progression of DR, along with recent efforts to normalize such alterations for better therapeutic outcome, will be underlined. In addition, current therapeutics and future directions for advancement of standard treatment for DR patients will be discussed.

Retinal vessel diameter, obesity and metabolic risk factors in school children (JuvenTUM 3)

BackgroundThe prevalence of childhood obesity is high and its association with future cardiovascular disease in adulthood is well established. The cross-sectional data presented analyze the prevalence of obesity and the association between metabolic risk factors, physical inactivity and retinal vessel diameter in young school children. MethodsThe examination included 578 school children aged 11.1±0.6years from secondary schools in the District of Munich, Germany. Anthropometric measurements and blood sampling were conducted using standard protocols for children. Physical activity was evaluated by use of a questionnaire. Retinal microvascular diameters and the arteriolar to venular ratio (AVR) were assessed with a non-mydriatic vessel analyser (SVA-T) using a computer-based program. ResultsIn our population, 128 (22.2%) children were overweight (ow) or obese (ob). The mean retinal arteriolar and venular calibres were 208.0±15.6μm and 236.2±16.2μm, respectively, with a mean AVR of 0.88±0.01. Girls had significantly wider arteriolar and venular diameters compared to boys (p<0.001). ow and ob children had a lower AVR compared to normal weight (nw) children (mean(95% CI); nw: 0.89(0.88–0.89); ow: 0.87(0.86–0.88); ob: 0.85(0.83–0.87); p≤0.05). Wider venular diameters were independently associated with higher BMI and higher hsCRP. Blood pressure was associated with retinal vessel constriction. Higher physical inactivity and BMI were independently associated with a reduced AVR (p=0.032 and p<0.001, respectively). ConclusionsCardiometabolic risk factors and physical inactivity are associated with retinal microvascular alterations in young children, comparable to associations in adults. Retinal vessel imaging seems to be a feasible assessment for the detection of microvascular impairments in children at risk of developing cardiovascular disease in adulthood.

ALTERATIONS OF RETINAL MICROVASCULAR NETWORK IN THE HIGH-NORMAL BLOOD PRESSURE STATE: EVIDENCE AND MECHANISMS: PP.35.449

Objective: Alterations of retinal vessels network are frequently detectable in established hypertension. Whether this is the case also in the high-normal blood pressure (BP) state is unknown. Design and Method: In 94 untreated patients of both genders (age 53.5 ± 2.1 yrs, mean ± SEM) with BP values in the high-normal range (ESH 2007 classification) we measured, along with anthropometric and haemodynamic variables, arterial-venular ratio (AVR), central retinal artery and vein equivalents {CRAE and CRVE, non-mydriatic retinography (TopCon TRC-NW200)}. Measurements included 24-hour ambulatory BP (90207 Spacelabs), left ventricular mass index (LVMI, echocardiography) and metabolic parameters (HOMA index, leptin, adiponectin and tumor necrosis factor 1). Results: In the population as a whole AVR was significantly and directly related to CRAE (r = 0.49, P < 0.005) and inversely to CRVE (r = -0,36,P < 0.01). 27.6% of the subjects showed an AVR value in the normal range (>0.92, control group), while 60% between 0.91 and 0.79 (group with mild arterial narrowing) and 13.4% < 0.78 (group with severe arterial narrowing). The arterial narrowing process was paralleled by an increase in clinic BP (130.7 ± 1.9/85 ± 1.7mmHg, 134.5 ± 2.1/86.1 ± 1.8mmHg and 139.2 ± 2.3/88.7 ± 2.0 mmHg), the AVR values being significantly and inversely related to clinic systolic BP (r = -0.75, P < 0,0001), night-time systolic BP (r = -0.24, P < 0.05) and to clinic DBP (r = -0.34, P < 0,005). LVMI showed a tendency to be greater in patients with reduced AVR. Metabolic and anthropometric parameters were similar in the 3 groups, the only exception being leptin, whose increase in patients with retinal alterations was inversely related to CRAE and CRVE (r = - 0.48 and r=-0.47 P < 0.01 for both). Conclusion: Thus retinal microvascular alterations are 1) of early appearance in the clinical course of hypertension and 2) of frequent detection in the high-normal BP state. They also suggest that the BP overload, particularly systolic, as well as hyperleptinemia (throughout an endothelial dysfunction and/or a sympathetic activation) may participate at the retinal microvascular disarray.

Importance de la réaction de Maillard en ophtalmologie

Non enzymatic glycosylation( glycation) of proteins, described by L. C. Maillard in 1912, results in the formation of advanced glycation end products (AGE-s). These exhibit a number of harmful reactions, increasing with age and involved in several age-associated pathologies. In ocular pathology, their role was demonstrated at several levels of age-associated eye-diseases, such as the rigidification of cornea, in the separation of vitreous fibers from the hyaluronan jelly, which might result in retinal detachment. AGE-s are involved also in retinal microvascular alterations in diabetics as well as in age-related macular degeneration. We compared the cytotoxic effect of several AGE-s on human skin fibroblasts and corneal keratocytes. Keratocytes were shown to be much more resistant to the cytotoxic effect of several AGE-products than fibroblasts. This higher resistance of keratocytes to the free radical mediated cytotoxic effect of AGE-s might be the result of the constant exposure of cornea to UV-light possibly mediating the appearance of more efficient protective mechanisms during evolution.

Retinopatia diabética

Diabetic retinopathy is a frequently observed complication in both type 1 and type 2 diabetes, specially in patients with long term disease and poor glicemic control. Irreversible visual loss appears at the final stages of diabetic retinopathy and it is considered one of the most tragic of diabetic complications. It is also considered an important factor of morbidity and has a high economical impact once it is the leading cause of blindness. The pathophysiology of the retinal microvascular alterations is related to the chronic hyperglycemia that leads to the following circulatory disturbances: loss of vascular tonus, increase in vascular permeability, edema and exudation, with vascular obstruction and ischemia that stimulates neovascularization, which may lead to fibrous retraction and vitreous hemorrhages with retinal detachment. Recent studies have indicated that the strict glicemic and blood pressure controls are effective in reducing or blocking the progression of retinopathy. Up to now no pharmacological agents have shown to be effective in preventing or reducing neovascularization and visual loss. Presently, the most effective available treatment for proliferative retinopathy is laser photocoagulation. Further studies are needed to obtain new products and technologies that could effectively prevent or block retinopathy progression.

A method of quantifying retinal microvascular alterations associated with blood pressure and age

To find an objective, sensitive method for quantifying microvascular alterations associated with level of blood pressure and age. A prospective cross-sectional study. Seventy-four previously untreated hypertensive patients, referred to a hospital outpatients department, and 26 normotensive volunteers participated. Twenty-four-hour ambulatory blood pressure monitoring and bilateral fundal photography were performed. The fundal photographs were projected on a screen such that the optic disc filled a circle of radius 5 cm. Microvessels crossing the border of a concentric circle of radius 20 cm were identified as arteriolar or venular, counted and their luminal diameters measured. Arteriolar and venular numbers, mean diameters and vascularities (arteriolar and venular vascularities defined as the sum of arteriolar and venular diameters, respectively). The technique was reproducible. As blood pressure increased, arteriolar vascularity declined and venular vascularity increased. These associations resulted in a strong inverse correlation between blood pressure level and the ratio arteriolar vascularity: venular vascularity (r = 0.48, P < 0.001). Arteriolar number declined with increasing diastolic blood pressure (r = 0.22, P < 0.05). Mean arteriolar diameter appeared to have a U-shaped relationship with diastolic blood pressure levels (r = 0.27, P < 0.05). Venular dilation was associated with increasing blood pressure levels (r = 0.22, P < 0.05). Mean arteriolar and venular diameters declined significantly with age (r = 0.33 and 0.26, respectively; P < 0.01) and there was no association between arteriolar vascularity:venular vascularity ratio and age. The method detected disparate retinal microvascular alterations with age and blood pressure. The arteriolar vascularity:venular vascularity ratio shows promise as a non-invasive, prognostic and therapeutic guide in hypertension.