Retinal Arteriolar Tortuosity Research Articles

The role of Perifoveal Arteriolar Tortuosity in Optical Coherence Tomography Angiography (OCTA) images as an early indicator of hypertensive retinopathy.

To assess the value of increased perifoveal retinal vascular tortuosity in optical coherence tomography angiography (OCTA) images as a biomarker of early hypertensive retinopathy and compare its clinical sensitivity and accuracy with traditional morphological changes used for Scheie classification. OCTA images of 81 eyes (40 eyes from 20 hypertensive subjects and 41 eyes from 21 control subjects) were obtained retrospectively. Hypertensive retinopathy changes in randomized eyes were graded according to the Scheie classification, and perifoveal vessels were traced in a masked fashion. Tortuosity values of the perifoveal vessels were then calculated along with interobserver agreement in determining the morphometric values. There were no differences in perifoveal venular tortuosity between the hypertensive and control groups (Mean = 1.13 ± 0.04 vs. 1.13 ± 0.03), but significant differences existed for arterioles (Mean = 1.14 ± 0.05 vs. 1.11 ± 0.04). Tortuosity measurements demonstrated a significant interobserver agreement (p < 0.001), while Scheie ratings had a poor interobserver agreement (p = 0.735). There was a significant difference in Scheie classification between the hypertensive and control groups (Mean = 1.06 ± 0.54 vs. 0.50 ± 0.43, p = 0.005). OCTA-based perifoveal retinal arteriolar tortuosity may be a potential reliable biomarker with certain advantages for detecting early hypertensive retinopathy than morphological changes used for the Scheie classification. This may have broad applications and establish important parameters in utilizing OCTA for screening protocols, considering the importance of early detection of systemic hypertension.

Retinal microvasculature and incident dementia over 10 years: The Three-City-Alienor cohort.

We explored the longitudinal relationship between retinal vascular features and dementia incidence over 10 years. Among 584 participants from the Three-City-Alienor (3C-Alienor) population-based cohort, quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were measured using semi-automated software. Dementia was actively diagnosed over the follow-up period. One hundred twenty-eight participants (21.9%) developed dementia over a median of 7.1 years. In Cox proportional hazards models adjusted for sociodemographic characteristics, apolipoprotein E (APOE) ε4, and vascular factors, increased retinal arteriolar tortuosity was associated with all-cause dementia (hazard ratio per standard deviation increase, 1.21; 95% confidence interval: 1.02-1.44). Wider retinal calibers and a higher venular tortuosity were associated with mixed/vascular dementia, but not Alzheimer's disease. Fractal dimensions were not associated with dementia. Changes in the retinal microvasculature were associated with dementia risk. More studies are needed to replicate these findings and determine which features might help identify persons at risk at an early stage. The retinal microvasculature might reflect the brain microvasculatureWe explored the association between retinal vascular features and incident dementia584 participants from the Three-City-Alienor cohort were followed-up over 10 yearsIncreased arteriolar tortuosity and venular calibers were associated with dementia riskRetinal imaging might help identify persons at risk of future dementia.

Ocular features in Williams-Beuren syndrome: a review of the literature.

The current review will discuss the pathophysiology, work-up and clinical relevance of the ocular phenotype in Williams-Beuren syndrome in detail. Few case reports, case series and retrospective studies reported the ophthalmic features in Williams-Beuren syndrome, focusing on specific aspects of the ocular involvement. Recently, novel retinal findings have been described in association with the disease. Numerous ocular features have been described in Williams-Beuren syndrome. Some of them, such as the stellate pattern of the iris or the retinal arteriolar tortuosity may be helpful for the diagnosis but have no significant clinical implications; others, such as strabismus and refractive errors require early treatment to reduce the risk of irreversible visual impairment. Finally, some features, such as a broad foveal pit and thinner retina still have unknown significance and require further longitudinal and multimodal studies.

Structural and functional analysis of retinal vasculature in HANAC syndrome with a novel intronic COL4A1 mutation.

Mutations of the COL4A1 gene, a major structural protein of vessels, may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography. Clinical data from six affected individuals (43 to 72years old) from a single family comprising two generations were collected. Imaging charts including conventional fundus imaging, OCT-angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband. DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120+2_1120+8del heterozygote). Four patients had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. By fundus examination, five had typical retinal arteriolar tortuosity with arteriolar loops. Wall-to-lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted in the two oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a higher flicker-induced vasodilation than a control population (6% to 11%; n<5%). Structural and dynamic analysis of retinal vessels in a HANAC family bearing a previously unreported intronic COL4 mutation was done. In addition to arteriolar tortuosity, we found reduced wall-to-lumen ratio, arteriolar irregularity and increased vasodilatory response to flicker light. These abnormalities were more marked in the oldest subjects. This abnormal flicker response affected also non-tortuous arteries, suggesting that microvascular dysfunction extends beyond tortuosity. Such explorations may help to better vascular dysfunction related to HANAC and hence better understand the mechanisms of end-organ damage.

Structural and functional exploration of the retinal vasculature in HANAC syndrome associated with a novel intronic COL4A1 mutation

AbstractPurpose: Mutations of the COL4A1 gene may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography.Methods: Clinical data from six affected individuals from a single family over two generations were collected. Imaging charts including conventional fundus imaging, OCT‐angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband.Results: DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120 + 2_1120 + 8del heterozygote). Four had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. Examination of retinal vessels showed that all patients had retinal arteriolar tortuosity which peaked in precapillary arterioles but spared capillaries and veins. Wall‐to‐lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted I the oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a high flicker‐induced vasodilation (from 6% to 10.8%; n &lt; 5%).Conclusions: Structural and dynamic analysis of retinal vessels in a HANAC family bearing a novel intronic COL4 mutation showed reduced parietal thickness, arteriolar irregularity and increased dilatory response to flicker light. This affected as well non tortuous arteries, suggesting that HANAC causes diffuse microvascular dysfunction. Our findings may help to better understand end‐organ damage related to HANAC.

Retinal microvasculature and risk of spontaneous abortion in multiethnic Southeast Asian women

To better understand the underlying pathogenesis of spontaneous abortion that affects 10%-20% of recognized pregnancies. We used retinal imaging to study the role of systemic microvasculature and the risk of spontaneous abortion. A prospective multiethnic preconception cohort study conducted in Singapore. Hospital-based. A total of 1,032 Southeast Asian women who intended to conceive naturally were screened at study entry, among which 480 women spontaneously conceived within the 12-month observation period. After excluding 24 women who were lost to follow-up, we calculated the spontaneous abortion rate among 456 women. Further, we included 379 women for the final association analysis because 63 women did not undergo preconception retinal imaging examination and 14 had other types of pregnancy loss instead of spontaneous abortion. Trained photographers performed retinal examination using a 45-degree nonmydriatic retinal camera at study entry during the preconception screening. Using a semiautomated, computer-based program, we assessed quantitative retinal microvascular measurements, including caliber, fractal dimension, curvature tortuosity, and branching angle. Clinical research coordinators collected information on sociodemographic status, menstrual characteristics, and lifestyle, and assessed blood pressure and anthropometry at study entry. We performed a modified Poisson regression model to estimate the relative risk (RR) and 95% confidence interval (CI) for each retinal microvascular feature and its association with spontaneous abortion after adjusting for major confounders such as maternal prepregnancy, body mass index, and previous pregnancy loss history. We reported a spontaneous abortion rate of 13.4% (61 out of 456). Among all retinal microvascular features, retinal arteriolar caliber, retinal arteriolar, and venular curvature tortuosity were associated with a high risk of incident spontaneous abortion. In the regression model, per SD increase in retinal curvature tortuosity was associated with a 25%-34% increased risk of incident spontaneous abortion (arteriolar: unadjusted RR, 1.29 [95% CI, 1.06-1.56] and adjusted RR, 1.26 [1.04-1.53]; venule: unadjusted RR, 1.30 [1.08-1.55] and adjusted RR, 1.34 [1.09-1.64]). Our prospective cohort observed an increased risk of spontaneous abortion among Asian women with more tortuous retinal vessels assessed during the preconception phase. Our results indicate a role of vascular inflammatory and oxidative stress in the pathogenesis of spontaneous abortion. ClinicalTrials.gov, NCT03531658.

Novel ophthalmic findings and deep phenotyping in Williams-Beuren syndrome

Background/AimsTo characterise the ocular manifestations of Williams-Beuren syndrome (WBS) and compare these to patients with isolated elastin mediated supravalvular aortic stenosis (SVAS).MethodsFifty-seven patients with a diagnosis of WBS and five...

Spontaneous Retinal Hemorrhages Associated with Familial Retinal Arteriolar Tortuosity

Spontaneous Retinal Hemorrhages Associated with Familial Retinal Arteriolar Tortuosity

Retinal arteriolar tortuosity and fractal dimension are associated with long-term cardiovascular outcomes in people with type 2 diabetes

Aims/hypothesisOur aim was to determine whether quantitative retinal traits in people with type 2 diabetes are independently associated with incident major cardiovascular events including CHD and stroke.MethodsA total of 1066 men and women with type 2 diabetes, aged 65–74 years, were followed up over 8 years in the population-based Edinburgh Type 2 Diabetes Study. Using retinal photographs taken at baseline and specialist software, a number of quantitative retinal traits were measured, including arteriolar and venular widths and tortuosity as well as fractal dimension (a measure of the branching pattern complexity of the retinal vasculature network). Incident CHD events occurring during follow-up included fatal and non-fatal myocardial infarction, first episodes of angina and coronary interventions for CHD. Incident cerebrovascular events included fatal and non-fatal stroke or transient ischaemic attack. Cox proportional hazard regression analyses were performed to identify the association of the retinal traits with cardiovascular events in the population with retinal data available (n = 1028).ResultsA total of 200 participants had an incident cardiovascular event (139 CHD and 61 cerebrovascular events). Following adjustment for age and sex, arteriolar tortuosity and fractal dimension were associated with cerebrovascular events (HR 1.27 [95% CI 1.02, 1.58] and HR 0.74 [95% CI 0.57, 0.95], respectively), including with stroke alone (HR 1.30 [95% CI 1.01, 1.66] and HR 0.73 [95% CI 0.56, 0.97], respectively). These associations persisted after further adjustment for established cardiovascular risk factors (HR 1.26 [95% CI 1.01, 1.58] and HR 0.73 [95% CI 0.56, 0.94], respectively). Associations generally reduced in strength after a final adjustment for the presence of diabetic retinopathy, but the association of fractal dimension with incident cerebrovascular events and stroke retained statistical significance (HR 0.73 [95% CI 0.57, 0.95] and HR 0.72 [95% CI 0.54, 0.97], respectively). Associations of retinal traits with CHD were generally weak and showed no evidence of statistical significance.Conclusions/interpretationArteriolar tortuosity and fractal dimension were associated with incident cerebrovascular events, independent of a wide range of traditional cardiovascular risk factors including diabetic retinopathy. These findings suggest potential for measurements of early retinal vasculature change to aid in the identification of people with type 2 diabetes who are at increased risk from stroke.Graphical abstract

Optic Disc Features in Familial Retinal Arteriolar Tortuosity.

Describing optic disc appearance in familial retinal arteriolar tortuosity (fRAT) using multimodal imaging and raising awareness of peripapillary arterial changes due to this disorder. A cross-sectional study was performed in four consecutive patients of two non-related families. Detailed ophthalmological examination was performed and supported by medical and family history and multimodal imaging. In all subjects, increased tortuosity of second- and third-order retinal arteries in superior and deeper vascular plexus was documented. Furthermore, tortuosity in the peripapillary circle of Zinn-Haller was found. In addition, retinal vessel oximetry confirmed tortuosity only of the arterial vessels. The present data suggests that a blurry bordered, hyperemic optic disc in the presence of abnormally tortuous arteriolar vessels and asymptomatically or oligosymptomatically spontaneously resolved hemorrhages could be associated with a fRAT. This finding could be linked to peripapillary arterial vessel tortuosity.

Association of reduced retinal arteriolar tortuosity with depression in older participants from the Northern Ireland Cohort for the Longitudinal Study of Ageing

IntroductionThe retina shares similar anatomical and physiological features with the brain and subtle variations in retinal microvascular parameters (RMPs) may reflect similar vascular variation in the brain. The aim of this study was to assess associations between RMPs and measures of depression in the Northern Ireland Cohort for the Longitudinal Study of Ageing.MethodsRMPs (arteriolar and venular caliber, fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Depression was characterised by the Centre for Epidemiologic Studies Depression Scale (CES-D) in the absence of mild cognitive impairment or use of anti-depressive medications. Associations between depression and RMPs were assessed by regression analyses with adjustment for potential confounders.ResultsData were available for 1376 participants of which 113 (8.2%) and 1263 (91.8%) were classified with and without depression. Participants had a mean age of 62.0 ± 8.4 yrs., 52% were female, and 8% were smokers. Individuals with depression had a higher CES-D score than those without (22.0 ± 6.2 versus 4.4 ± 3.9). Lower values of arteriolar tortuosity were significantly associated with depression, before and after adjustment for potential confounders (odds ratio = 0.79; 95% confidence intervals: 0.65, 0.96; P = 0.02).ConclusionDecreased retinal arteriolar tortuosity, a measure of the complexity of the retinal microvasculature was associated with depression in older adults independent of potential confounding factors. Retinal measures may offer opportunistic assessment of microvascular health associated with outcomes of depression.

High-salt intake affects retinal vascular tortuosity in healthy males: an exploratory randomized cross-over trial

The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal microcirculation is currently unknown. Therefore, we performed an exploratory randomized cross-over dietary intervention study in 18 healthy males. All subjects adhered to a two-week high-salt diet and low-salt diet, in randomized order, after which fundus photographs were taken and assessed using a semi-automated computer-assisted program (SIVA, version 4.0). Outcome parameters involved retinal venular and arteriolar tortuosity, vessel diameter, branching angle and fractal dimension. At baseline, participants had a mean (SD) age of 29.8 (4.4) years and blood pressure of 117 (9)/73 (5) mmHg. Overall, high-salt diet significantly increased venular tortuosity (12.2%, p = 0.001). Other retinal parameters were not significantly different between diets. Changes in arteriolar tortuosity correlated with changes in ambulatory systolic blood pressure (r = − 0.513; p = 0.04). In conclusion, high-salt diet increases retinal venular tortuosity, and salt-induced increases in ambulatory systolic blood pressure associate with decreases in retinal arteriolar tortuosity. Besides potential eye-specific consequences, both phenomena have previously been associated with hypertension and other cardiovascular risk factors, underlining the deleterious microcirculatory effects of high salt intake.

Microvascular changes of the retina in ankylosing spondylitis, and the association with cardiovascular disease – the eye for a heart study

ObjectiveAnkylosing spondylitis (AS) is associated with an increased risk of cardiovascular disease (CVD). Microvasculature changes can precede overt CVD, but have been studied poorly in AS. The retinal vasculature is easily accessible and changes are associated with CVD (e.g. arteriolar narrowing, venular widening, loss of tortuosity). This proof of concept study compared the retinal microvasculature of AS patients with healthy controls, and the influence of gender. MethodsCross-sectional case-control study comparing AS patients with healthy controls. Main inclusion criteria were: age 50–75 years, no diabetes mellitus and, for AS, fulfillment of the modified New York criteria. All subjects underwent fundus photography, analyzed with Singapore I Vessel Assessment software, and Optical Coherence Tomography Angiography (OCTA). Subjects were compared with generalized estimating equations (GEE). Multivariable analyses were adjusted for demographics and cardiovascular risk, and stratified for gender. ResultsFifty-nine AS patients and 105 controls were included (50% women). Controls were significantly older than patients (68 versus 60, p<0.01), but did not differ in cardiovascular profile. Patients had a lower retinal arteriolar tortuosity (β ̶-0.1, 95%CI [-0.2; -0.01], p = 0.02), and higher vessel density (β 0.5, 95% CI [0.1; 0.9], p = 0.02). In addition, male AS patients showed a lower arteriovenular ratio compared to male controls (β -0.03, p = 0.04, 95%CI [-0.05; -0.001]). There were no differences found between women with and without AS. ConclusionThis study detected several retinal microvascular changes, in AS patients compared to controls, which have been associated with CVD. Retinal imaging might be an interesting tool for future CVD screening.

Asymptomatic familial bilateral severe retinal vascular tortuosity

A 15-year-old girl and her 40-year-old mother presented with abnormal fundi, with significant tortuosity of the retinal vessels in both eyes. They were asymptomatic and had no other abnormal findings. Furthermore, systemic complications were not confirmed. Familial retinal arteriolar tortuosity (FRAT) is a rare hereditary disease that is very similar to that observed in our patients. The condition of our patients differs from FRAT in that it was accompanied by severe venous tortuosity. No similar cases have been previously reported.

Bilateral and multiple sub-internal limiting membrane hemorrhages in a familial retinal arteriolar tortuosity patient by Valsalva-like mechanism: an observational case report

BackgroundBilateral and multiple Valsalva-related sub-internal limiting membrane (ILM) hemorrhages in a familial retinal arteriolar tortuosity (FRAT) patient is rare, and we treated this patient by both observation and Neodymium yttrium aluminum garnet (Nd: YAG) laser membranotomy methods.Case presentationA 13-year-old female student presented with sudden visual loss and central scotoma in both eyes after running 800 m at the school gym. The examination revealed six sub-ILM hemorrhages with the biggest hemorrhage measuring approximately 1.5-disc diameters (DD) in the right eye and two sub-ILM hemorrhages with the biggest one measuring 5.5 DD in the left eye. The patient was diagnosed as having Valsalva retinopathy associated with FRAT. Nd: YAG laser membranotomy was performed at the biggest hemorrhages and the rest hemorrhages were treated with observation in both eyes. The visual acuity recovered to 20/16 in the right eye and 20/20 in the left eye. Epiretinal membrane (ERM) formation was observed in the left eye.ConclusionsNd: YAG laser could be considered for treating premacular hemorrhage in FRAT patient especially when a quick vision recovery was needed. This is the first reported case of a FRAT patient suffering from bilateral and multiple Valsalva-related sub-ILM hemorrhages which were treated by both observation and Nd: YAG laser treatment.

High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report

BackgroundCongenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses.Case presentationThe proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation.ConclusionsIn addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.

Tortuosity of Retinal Main and Branching Arterioles, Venules in Patients With Type 2 Diabetes and Diabetic Retinopathy in China

The epidemic studies have demonstrated an excessively increase of diabetic patients in recent years, who are at high risk of developing microvascular complications. Those microvascular complications usually lead to chronic health problems, e.g. diabetic retinopathy (DR), thus early and regular screening is indeed necessary. Retinal vascular tortuosity, which is one of geometrical parameters related to microvascular morphological changes, has been investigated in many studies related to diabetes, diabetic risk factors and diabetic complications. However, the global tortuosity of retinal vessels in DR progression is quantified either subjectively or imprecisely in those previous studies. Furthermore, to our best knowledge, the association of tortuosity, diabetes and DR has never been investigated based on a Chinese population-based cohort, even though it accounts for more than 30% of diabetic patients worldwide. Therefore, it is of great necessary and clinical significance to extract retinal tortuosity in a more reliable way and explore its associations with diabetic risk factors and DR severity in China. In this study, high contrast retinal images from 495 Chinese patients with type 2 diabetes were acquired by confocal scanning laser ophthalmoscope and the global tortuosity was extracted from main and branching arterioles, venules in the whole retinal image based on the theory of best-fit exponential curves in the roto-translation group SE(2). The statistical analysis results show that retinal arteriolar and venular tortuosity might be remarkable indices for assessing retinopathy severity and identifying individuals with high-risk of renal disease in diabetes, which may provide additional insights on microvascular changes for diabetic retina and kidney diseases.

Association between Retinal Vascular Geometric Changes and Cognitive Impairment: A Systematic Review and Meta-Analysis.

Background and PurposePrevious studies have explored the association between retinal vascular changes and cognitive impairment. The retinal vasculature shares some characteristics with the cerebral vasculature, and quantitative changes in it could indicate cognitive impairment. Hence, a comprehensive meta-analysis was performed to clarify the potential relationship between retinal vascular geometric changes and cognitive impairment.MethodsRelevant databases were scrupulously and systematically searched for retinal vascular geometric changes including caliber, tortuosity, and fractal dimension (FD), and for cognitive impairment. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of included studies. RevMan was used to perform the meta-analysis and detect publication bias. Sensitivity analyses were also performed.ResultsFive studies that involved 2,343 subjects were finally included in the meta-analysis. The results showed that there was no significant association between central retinal artery equivalents (Z=1.17) or central retinal venular equivalents (Z=1.74) and cognitive impairment (both p>0.05). Similarly, no significant difference was detected in retinal arteriolar tortuosity (Z=0.91) and venular tortuosity (Z=1.31) (both p>0.05). However, the retinal arteriolar FD (mean difference: −0.03, 95% CI: −0.05, −0.01) and venular FD (mean difference: −0.03, 95% CI: −0.05, −0.02) were associated with cognitive impairment.ConclusionsA smaller retinal microvascular FD might be associated with cognitive impairment. Further large-sample and well-controlled original studies are required to confirm the present findings.

Association between Coronary Artery Measurements and Retinal Microvasculature in Children with New Onset of Kawasaki Disease

About a quarter of children with new onset of Kawasaki disease (KD) encounter coronary arterial involvement. While KD is known to cause vasculitis of medium-sized vessels, few studies have been done to study the involvement of the microcirculation. We aimed to investigate the association between coronary arterial dilatation and retinal microvasculature in a pilot setting, in order to further study the pathophysiological mechanism of KD from the perspective of small vessels changes. We performed a cross-sectional, observational, hospital-based study on 11 children aged 2 years and above with new-onset KD. Cardiac imaging technicians performed the echocardiographic examinations and recorded right coronary artery (RCA), left coronary artery (LCA) and left anterior descending artery (LAD). Qualified retinal graders reviewed and graded standardised retinal photographs to assess retinal microvascular parameters. Among 11 participants, there were 7 boys and 4 girls. Median and interquartile range of participants’ age were 5.92 (3.08) years. After adjusting for age and sex, each unit increase in LAD (mm) was significantly associated with increment of retinal arteriolar tortuosity (4.25 × 10−5 units, 95% Confidence Interval: 1.19, 7.32). Retinal arteriolar geometric changes were associated with LAD dilatation in 11 children with new onset of KD. Our pilot provided proof-of-concept that retinal imaging might be useful for detecting coronary arterial involvement in young children with KD and it needs further investigation.

Novel Genetic Locus Influencing Retinal Venular Tortuosity Is Also Associated With Risk of Coronary Artery Disease.

The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity (TortV), and one at 13q34 (COL4A2) for retinal arteriolar tortuosity (TortA); these 2 loci were subsequently confirmed in 3 independent cohorts (Ntotal=1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4/CAPN12 was rs1808382 (βs.d.=-0.109; SE=0.015; P=2.39×10-13) and in COL4A2 was rs7991229 (βs.d.=0.103; SE=0.015; P=4.66×10-12). Notably, the ACTN4/CAPN12 locus associated with TortV is also associated with coronary artery disease, heart rate, and atrial fibrillation. Genetic determinants of retinal vascular tortuosity are also linked to cardiovascular health. These findings provide a molecular pathophysiological foundation for the use of retinal vascular traits as biomarkers for cardiovascular diseases.