Retinal Vascular Caliber Changes Research Articles

Retinal Venule Coverage by Pericytes Decreases in Multiparous Mice in a Time-Dependent Manner Post-Delivery.

Structural changes in the retinal vasculature have been linked to increased cardiovascular risks and also change as a function of age. Because multiparity has been associated with poorer cardiovascular health scores, we hypothesized that changes in retinal vascular caliber would be observed in multiparous, compared to nulliparous, females and retired breeder males. Age-matched nulliparous (n = 6) and multiparous (n = 11, retired breeder females with 4 ± 1 litters), and male breeder (n = 7) SMA-GFP reporter mice were included for assessment of retinal vascular structure. Multiparous females had higher body mass, heart weight, and kidney weight compared to nulliparous mice, with lower kidney and higher brain weight compared to male breeders. There was no difference in number of retinal arterioles or venules, or arteriole or venule diameter among groups; however, venous pericyte density (number per venule area) decreased in multiparous vs. nulliparous mice and was negatively associated with the time since last litter and with age. Our results suggest that the time elapsed since delivery is an important factor to be considered in multiparity studies. Taken together, changes in vascular structure and potentially function, are time- and age-dependent. Ongoing and future work will determine whether structural changes are associated with functional consequences at the blood-retinal barrier.

Retinal vascular caliber in patients with newly diagnosed iron deficiency anemia

BackgroundTo evaluate the retinal vascular caliber using fundus photography in patients with newly diagnosed iron deficiency anemia (IDA). MethodsThis study included 56 eyes of 28 female patients with IDA and the 56 eyes of 28 age- and sex-matched healthy participants. Retinal vascular calibers were measured using image analysis software from fundus photographs. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and arteriole-to-venule ratio (AVR) were compared between groups. Linear regression analysis was used to quantify the relative impact of hemoglobin level on CRAE, CRVE, and AVR. ResultsThe CRAE was significantly narrower in patients with IDA. However, no such difference appeared between groups in CRVE. AVR was significantly lower among patients with IDA than in the control group. Linear regression analysis revealed that in patients with IDA, hemoglobin level was associated with CRAE and CRVE but not with AVR. Among non-anemic individuals, there was also no association between hemoglobin level and CRAE, CRVE, or AVR. ConclusionsOur results showing that the CRAE is significantly narrower in patients with IDA than in healthy non-anemic individuals suggests that vascular caliber may reflect early microvascular alterations resulting from IDA. Added to that, hemoglobin level was associated with CRAE and CRVE in our linear regression analysis of patients with IDA. Certain changes in retinal vascular caliber are also clearly associated with high blood pressure, cardiovascular risk, and mortality. It may be critical to identify all alterations in retinal vascular caliber in order to prevent potential ocular and systemic disorders in patients with IDA.

Retinal Vascular Caliber Changes in Early Type 2 Diabetic Patients without Retinopathy

Purpose: To evaluate the retinal vascular caliber in early type 2 diabetic patients without retinopathy.Methods: This retrospective study reviewed the medical records of 85 patients who were diagnosed with type 2 diabetes (age, 10-48 years) and sex-matched healthy controls. Dilated fundus examinations were performed to confirm the absence of diabetic retinopathy. Fundus photographs were acquired and analyzed using software that semi-automatically measured retinal vascular caliber. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were determined using the revised Parr-Hubbard formula. Healthy controls were examined using the same approach.Results: There were no significant differences between patients and controls in terms of CRAE (149.92 ± 21.29 µm and 144.85 ± 17.14 µm, respectively; p = 0.137) or CRVE (195.85 ± 22.94 µm and 196.69 ± 18.43 µm, respectively; p = 0.829). However, AVR was significantly higher in the patient group (0.768 ± 0.088 vs. 0.737 ± 0.061; p = 0.031). In the patient group, AVR was significantly correlated with hemoglobin A1c (r = 0.325, p = 0.006), but not with body mass index (p = 0.478).Conclusions: An increase in peripapillary AVR may be an early feature of retinal vessels observed in patients with type 2 diabetes, which is closely related to elevated blood sugar.

Retinal vascular caliber in turkish adolescents with type 1 diabetes mellitus

Diabetic retinopathy (DR) is a common result of diabetes mellitus (DM). Alterations in retinal vascular caliber may be early finding of diabetic retinopathy. The aim of this study is to demonstrate retinal vascular caliber changes in Turkish adolescents with type 1 diabetes mellitus (T1D). This prospective and cross-sectional study included 108 eyes of the T1D adolescents and 75 eyes of the age-sex matched control group. Fundus images of the both groups were taken with fundus camera system (FA; Visucam500; Carl Zeiss Meditec, Jena, Germany) and were analyzed with IVAN which is a semi-automated system used to measure the width of retinal vessels using a digital retinal image (Nicole J. Ferrier, College of Engineering, Fundus Photography Reading Center, University of Wisconsin, Madison, WI, USA). Central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and artery-vein ratio (AVR) were compared between groups. Both groups were comparable in baseline characteristics (p>0.05). The mean CRAE value was higher in T1D group (179.03±29.58 µ in T1D group and 166.64±15.76 µ in control group, p

Retinal vascular caliber changes after laser photocoagulation in diabetic retinopathy

BACKGROUND Diabetic retinopathy causes vascular dilatation caused by hypoxia, whereas oxygen tension improvement leads to retinal vessels narrowing. Given that laser photocoagulation aims to increase the oxygen tension in the retina, we hypothesized that the narrowing of vessel caliber after the treatment could be possibly demonstrated. This study aimed to assess the changes in the caliber of retinal vessels before and after laser photocoagulation in diabetic retinopathy.
 METHODS This research was a prospective cohort study on the treatment of diabetic retinopathy by laser photocoagulation, and it was conducted at Universitas Hasanuddin Hospital, Makassar, Indonesia between November 2017–April 2018. Retinal vascular caliber changes were analyzed before and 6–8 weeks after photocoagulation in 30 diabetic eyes. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured using the vessel assessment and measurement platform software for images of the retina (VAMPIRE) manual annotation tool.
 RESULTS A significant decrease of CRVE was observed after laser photocoagulation (p<0.001), but CRAE was not reduced significantly (p = 0.067). No difference was recorded between CRVE and CRAE post-laser photocoagulation (p = 0.14), implying a reduction in vein caliber toward normal in the treated eyes.
 CONCLUSIONS Laser photocoagulation decreases the CRVE in diabetic retinopathy despite the absence of changes in the grade of diabetic retinopathy.

Retinal vascular diameter changes assessed with a computer-assisted software after strabismus surgery.

To quantitatively investigate the retinal vascular diameter changes, analyzing the early and long-term effects on the retinal circulation, with 6-month follow-up. Patients underwent horizontal strabismus surgery were enrolled prospectively. Retinal vessel diameters on color fundus photographs were assessed before and 1, 7d, 6mo after surgery, using a computer-assisted quantitative assessment software. To evaluate the retinal vascular caliber changes, retinal vascular diameters were calculated by means of the Parr-Hubbard formula as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). The arteriovenous ratio (AVR) was calculated as CRAE divided by CRVE. A total of 154 eyes of 104 consecutive patients were included. Compared with the data before surgery (121.55±24.67), the mean CRAE (131.18±28.29) significantly increased 1d after surgery (P=0.003), but went back to baseline level at 7d (118.89±30.35, P=0.15), and 6mo (123.22±15.32, P=0.60), so did the AVR (P<0.001, P=0.08, P=0.07). As for the mean CRVE, there was no significant difference between those four time points (172.43±33.25, 175.57±36.98, 174.03±40.18, 174.86±20.46, P=1.00). Strabismus surgery on both lateral and media rectus muscles, or single media rectus muscle may increase retinal blood flow during the early postoperative period, but would return to normal later. The number of transected anterior ciliary arteries rather might be the main cause of retinal hemodynamic changes early after strabismus surgery.

Retinal Vascular Caliber Changes After Topical Nepafenac Treatment for Diabetic Macular Edema

ABSTRACTPurpose: To assess changes in retinal vascular caliber in response to short-term use of nepafenac eye drops in patients with mild diabetic macular edema.Materials and methods: Thirty-four patients with previously untreated bilateral mild diabetic macular edema were included in this prospective study. For each participant, one eye was randomly assigned to nepafenac treatment (0.1%, three times/day) and the other eye was left untreated throughout the study. Using digital fundus photographs, retinal vascular calibers were calculated and compared in treated and untreated eyes at the baseline, week 1, and week 6.Results: Baseline vessel diameters did not differ in treated and fellow eyes (p > 0.05). Over the 6 weeks of the study, significant vasoconstriction of the retinal arteriolar caliber was observed at weeks 1 (p < 0.05) and 6 (p < 0.05), while an unchanged retinal venular caliber was noted between the treated and untreated eyes (p > 0.44). Significant macular thickness difference was only observed at week 6 (p = 0.002).Conclusions: Topical nepafenac has a significant narrowing effect on the retinal arteriolar diameter and a significant reductive effect on central macular thickness in eyes with mild diabetic retinopathy.

Assessing the Causality between Blood Pressure and Retinal Vascular Caliber through Mendelian Randomisation.

We aimed to determine the association between blood pressure (BP) and retinal vascular caliber changes that were free from confounders and reverse causation by using Mendelian randomisation. A total of 6528 participants from a multi-ethnic cohort (Chinese, Malays, and Indians) in Singapore were included in this study. Retinal arteriolar and venular caliber was measured by a semi-automated computer program. Genotyping was done using Illumina 610-quad chips. Meta-analysis of association between BP, and retinal arteriolar and venular caliber across three ethnic groups was performed both in conventional linear regression and Mendelian randomisation framework with a genetic risk score of BP as an instrumental variable. In multiple linear regression models, each 10 mm Hg increase in systolic BP, diastolic BP, and mean arterial BP (MAP) was associated with significant decreases in retinal arteriolar caliber of a 1.4, 3.0, and 2.6 μm, and significant decreases in retinal venular caliber of a 0.6, 0.7, and 0.9 μm, respectively. In a Mendelian randomisation model, only associations between DBP and MAP and retinal arteriolar narrowing remained yet its significance was greatly reduced. Our data showed weak evidence of a causal relationship between elevated BP and retinal arteriolar narrowing.

Retinal Vascular Caliber Changes in Diabetic Retinopathy after Panretinal Photocoagulation and Additive Bevacizumab Injections

Retinal Vascular Caliber Changes in Diabetic Retinopathy after Panretinal Photocoagulation and Additive Bevacizumab Injections

Retinal Microvasculature in Alzheimer's Disease

Although cerebral small vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. As the retina and the brain share similar embryological origin, anatomical features and physiological properties with the cerebral small vessels, the retinal vessels thus offer a unique and easily accessible "window" to study the correlates and consequences of cerebral small vessel diseases in vivo. Retinal microvasculature can now be visualized, quantified and monitored non-invasively using state-of-the-art retinal imaging technology. Recent clinic- and population-based studies have demonstrated a link between retinal vascular changes and dementia, in particular AD, and cerebral small vessel disease. In this review, we summarize the current findings on retinal vascular changes such as retinopathy signs and changes in novel retinal vascular network parameters and retinal vascular caliber with dementia, cognitive dysfunction and cerebral small vessel disease, and discuss possible future research to further evaluate whether retinal vascular imaging might help to elucidate vascular mechanisms contributing to the development of AD and provide additional value in predicting who may be at risk of developing AD.

The Relationship between Changes in Body Mass Index and Retinal Vascular Caliber in Children

To examine the longitudinal relationship between changes in childhood body mass index (BMI) and retinal vascular caliber. A prospective study of 421 healthy children aged 7-9 years in 2001 who returned for follow-up in 2006. At both visits, retinal photographs and anthropometric measurements were taken following standardized protocols. Retinal arteriolar and venular calibers were measured using a computer-based program and summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). At follow-up, mean weight, height, and BMI increased significantly (P < .001). Mean CRVE increased by 3.4 μm (P < .001) but mean CRAE did not alter significantly (P = .340). On multivariate analysis, greater BMI was cross-sectionally associated with narrower CRAE (P < .01) and wider CRVE (P < .01). On longitudinal analysis, increasing BMI was associated with increasing CRVE (P = .04) over the 5-year period. Baseline BMI was associated with increased venular caliber and decreased arteriolar caliber at follow-up, and vice versa (P < .05). Increasing BMI is associated with increasing retinal venular caliber over time in children, and baseline retinal vascular caliber changes increase the risk of higher BMI at follow-up. As both widened retinal venular caliber and greater BMI are associated with risk of cardiovascular events in adults, progressive retinal venular widening could be a manifestation of an adverse microvascular effect of obesity early in life.

Retinal Microvasculature as a Model to Study the Manifestations of Hypertension

The retinal vasculature allows direct noninvasive visualization of the body's mircrovasculature. Because the retina and other end organs (brain and kidney) share similar anatomical features and physiological properties, the retinal vessels offer a unique and easily accessible window to study the health and disease of the human microcirculation. Advanced retinal vascular imaging technologies have been developed to allow a more objective and precise assessment of retinal vascular changes. The changes in the retinal vasculature associated with hypertension can be broadly divided into 3 groups: (1) classic retinal vascular changes in response to blood pressure (referred to as hypertensive retinopathy signs), (2) changes in retinal vascular caliber, and (3) changes in more global geometrical patterns of the retina. In this review, we summarize the current understanding of the relationship between retinal vascular changes and blood pressure, the evidence for the retinal vasculature as a biological model to study the manifestation and early pathogenic correlates of hypertension, the latest advances in retinal vascular imaging technologies, and the future opportunities and challenges of retinal vascular imaging. We suggest that further development of retinal vascular analyses and standardized measurement protocols, evaluation of the clinical use of retinal vascular imaging in assessing cardiovascular risk prediction, and using retinal vascular imaging to test antihypertensive treatments will allow the translation of retinal vascular imaging as a tool to improve the diagnosis, prognosis, and management of hypertension in clinical practice.

Effect of Image Compression and Resolution on Retinal Vascular Caliber

Changes in retinal vascular caliber measured from digital color fundus photographs have been independently associated with systemic outcomes in epidemiologic studies, but the effect of image resolution and compression on vascular measurements has not been previously evaluated. To explore image compression, 40 natively digital fundus images were selected with good photo quality, high spatial resolution, and no previous image compression. Using Adobe Photoshop, these images were compressed at progressively higher levels up to 147:1, and then retinal vascular caliber was measured at each level using semiautomated software. To examine resolution, 40 fundus photographs acquired on high-resolution film were scanned with settings corresponding to 10, 7, 5, 3, and 1 megapixel fundus cameras. After adjusting for scale factor, vascular caliber was measured at each level of resolution. Data were analyzed by comparing the calculated central retinal arteriole equivalent (CRAE) and the central retinal venular equivalent (CRVE) of the original and altered images, using repeated measures ANOVA. CRAE became significantly wider with increasing levels of compression at the 25:1 threshold (~1 μm wider, P < 0.001) and was ~5 μm wider with 147:1 compression. CRVE also increased, but less than CRAE. Using 7 (megapixel)-MP resolution as the standard, CRVE was significantly narrower at the 5-MP simulation (~2 μm, P < 0.001) and was ~12 μm narrower at the 1-MP simulation. CRAE also decreased, but less than CRVE. Increasing digital image file compression and decreasing fundus image spatial resolution led to skewed measurements of the retinal vascular caliber.

Proteasome modulator 9 is linked to microvascular pathology of T2D

The locus 12q24 is linked to type 2 diabetes (T2D) and to changes in retinal vascular caliber in Caucasians. Proteasome Modulator 9 gene (PSMD9) lies in the 12q24 locus and is implicated in diabetes onset and in degradation of intracellular proteins in antigenic peptides in the immune response to antigen presentation by MHC class I cells. Within PSMD9, we reported a linkage to T2D and to MODY3 in Italian families. We recently demonstrated a linkage of the PSMD9 T2D risk SNPs with T2D-nephropathy, T2D-neuropathy, retinopathy, hypercholesterolemia, and macrovascular pathology. We aimed at studying the presence of the linkage signal of the PSMD9 T2D risk SNPs IVS3 + nt460, IVS3 + nt437, E197G to microvascular pathology associated to T2D in Italian siblings/families. We screened 200 T2D siblings/families for the PSMD9 above-mentioned variants and performed a parametric and non-parametric linkage study by Merlin software. Our results show significant LOD score in linkage with microvascular pathology for the PSMD9 SNPs studied using the non-parametric and parametric linkage analysis. The strongest signal is present under the recessive model. Our statistical power relies on the presence of T2D affected siblings, which represent an ideal dataset to identify linkage with a recessive disease model. Our simulation analysis confirms that the results are not due to random chance. In summary, the PSMD9 IVS3 + nt460, IVS3 + nt437, E197G SNPs are linked via the recessive model to microvascular pathology of T2D in Italians. A possible role of PSMD9 in microvascular pathology may be related to a causative pathogenetic role in inflammation as part of an autoimmune process.

Retinal Vascular Caliber Changes on OCT after Intravitreal Bevacizumab Injection in Diabetic Macular Edema

Retinal Vascular Caliber Changes on OCT after Intravitreal Bevacizumab Injection in Diabetic Macular Edema

Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10−8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%–3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10−25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10−16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10−13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10−16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

Retinal microvascular structure: determinants and potential utility of novel imaging measurements

The retinal microvasculature is a ‘window’ to the systemic circulation. Advancement of computer-assisted techniques to assess vascular structural characteristics from retinal images offers a unique opportunity in circulation research via a direct view of the human microcirculatory system in vivo. Recent studies demonstrate that retinal vascular caliber changes are predictive of development of hypertension, cardiovascular events and Type 2 diabetes mellitus. More importantly, a number of major cardiovascular (e.g., elevated blood pressure, diabetes, lipid levels and obesity) and lifestyle-related (e.g., smoking and alcohol consumption) risk factors are found to be associated with the variations of small vessel caliber. Retinal vascular caliber may therefore represent sub-clinical alterations proceeding to clinical stages of cardiovascular events. Further studies of other parameters of retinal microvascular structure (e.g., tortuosity and branching angle) to determine their associations with genetic factors and responses to treatment strategies may provide clinical applications of these measures on the changes of retinal microvasculature.

Retinal Vascular Caliber and Brachial Flow-Mediated Dilation

Retinal vascular caliber changes have been shown to predict stroke, but the underlying mechanism of this association is unknown. We examined the relationship between retinal vascular caliber with brachial flow-mediated dilation (FMD), a measure of systemic endothelial function. The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of persons 45 to 84 years of age residing in 6 US communities free of clinical cardiovascular disease at baseline. Brachial FMD data were collected at baseline (July 2000 to June 2002), and retinal vascular caliber was measured from digital retinal photographs at the second examination, immediately after the first (August 2002 to January 2004). Data were available for 2851 participants for analysis. The mean brachial FMD was 4.39+/-2.79%. After adjusting for age and gender, brachial FMD was reduced in persons with wider retinal venular caliber (changes in FMD -0.25, 95% CI, -0.36, - 0.13; P<0.001, per SD increase in venular caliber). This relationship persists after adjusting for systolic blood pressure, serum total cholesterol, use of lipid-lowering and antihypertensive medication, body mass index, current smoking status, and hemoglobinA(1C) (-0.18; 95% CI -0.30, - 0.06; P=0.004, per SD increase in venular caliber). Brachial FMD was not associated with retinal arteriolar caliber. Persons with wider retinal venules have reduced brachial FMD, independent of other vascular risk factors. This suggests that retinal venular caliber, previously shown to predict stroke, may be a marker of underlying systemic endothelial dysfunction.

Retinal Vessel Caliber and Peripheral Neuropathy in Diabetic Participants

Retinal vascular caliber changes predict diabetic microvascular complications such as retinopathy, and nephropathy. However, the association between retinal vasculature and peripheral neuropathy is not well studied. We evaluated the association between retinal vascular caliber and peripheral neuropathy in a multi-ethnic Asian population with diabetes (n = 423) in Singapore. Retinal arteriolar and venular caliber was measured from digital retinal photographs and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent. Peripheral neuropathy was defined from neurothesiometer or monofilament sensory testing. Larger CRAE was positively associated with peripheral neuropathy independent of age, sex, ethnicity, current smoking, alcohol consumption, body mass index, total cholesterol, systolic blood pressure, and duration of diabetes. The multivariable odds ratio (OR) [95% confidence interval (CI)] of peripheral neuropathy was 2.81 (1.38-5.73) comparing highest vs. lower three quartiles of CRAE. This association was consistently present in analyses stratified by age, sex and ethnicity. Retinal venular caliber was not associated with peripheral neuropathy. These data suggest that larger retinal arteriolar diameters are associated with peripheral neuropathy independent of major risk factors.

Correlation of Light-Flicker–Induced Retinal Vasodilation and Retinal Vascular Caliber Measurements in Diabetes

Subtle changes in retinal vascular caliber have been shown to predict diabetic retinopathy and other diabetic complications. This study was undertaken to investigate whether retinal vascular caliber correlates with light-flicker-induced retinal vasodilation, a measure of endothelial function. The participants were 224 persons with diabetes (85 type 1 and 139 type 2) and 103 persons without diabetes (controls). Flicker-induced retinal vasodilation (percentage increase over baseline diameter) was measured with a vessel analyzer. Retinal vascular caliber was measured from digital retinal photographs according to a standardized, validated protocol. Data from both right and left eyes were used and modeled with generalized estimating equations to account for correlation between eyes. In persons with diabetes, after adjustment for age and sex, reduced flicker-induced vasodilation was associated with wider retinal vascular caliber. Eyes with the lowest tertiles of flicker-induced arteriolar dilation had wider arteriolar caliber (5.40 mum; 95% confidence interval [CI], 1.76-9.05) and eyes with the lowest tertiles of flicker-induced venular dilation had corresponding wider venular caliber (12.4 mum; 95% CI, 6.48-18.2), respectively, than eyes with the highest tertile of vasodilation. These associations persisted after further adjusting for diabetes duration, systolic blood pressure, fasting glucose, lipids, body mass index, current smoking, and presence of diabetic retinopathy. No associations were evident in persons without diabetes. Changes in retinal vascular caliber (wider arterioles and venules) are associated with impaired flicker-induced vasodilation in persons with diabetes. Determining whether endothelial dysfunction explains the link between retinal vascular caliber and risks of diabetic microvascular complications calls for further study.