Retinal Vascular Tortuosity, Blood Pressure, and Cardiovascular Risk Factors

doi:10.1016/j.ophtha.2010.08.045

Ophthalmology

Volume 118, Issue 5, May 2011, Pages 812-818

https://doi.org/10.1016/j.ophtha.2010.08.045 Get rights and content

Objective

To examine the relationship of retinal vascular tortuosity to age, blood pressure, and other cardiovascular risk factors.

Design

Population-based, cross-sectional study.

Participants

A total of 3280 participants aged 40 to 80 years from the Singapore Malay Eye Study (78.7% response rate).

Methods

Retinal arteriolar and venular (vascular) tortuosity were quantitatively measured from fundus images using a computer-assisted program. Retinal vascular tortuosity was defined as the integral of the curvature square along the path of the vessel, normalized by the total path length. Data on blood pressure and major cardiovascular disease (CVD) risk factors were collected from all participants.

Mean Outcome Measures

Retinal arteriolar and venular tortuosity.

Results

A total of 2915 participants contributed data to this study. The mean (standard deviation) and median were 2.99 (1.40) and 2.73 for retinal arteriolar tortuosity (×10⁴), and 4.64 (2.39) and 4.19 for retinal venular tortuosity (×10⁴), respectively. Retinal venules were significantly more tortuous than retinal arterioles (P < 0.001). In multivariable-adjusted linear regression models, less arteriolar tortuosity was independently associated with older age, higher blood pressure, higher body mass index (BMI), and narrower retinal arteriolar caliber (all P < 0.05); greater venular tortuosity was independently associated with younger age, higher blood pressure, lower high-density lipoprotein (HDL) cholesterol level, and wider retinal venular caliber (all P < 0.05).

Conclusions

Retinal arteriolar tortuosity was associated with older age and higher levels of blood pressure and BMI, whereas venular tortuosity was also associated with lower HDL level. The quantitative assessment of retinal vascular tortuosity from retinal images may provide further information regarding effects of cardiovascular risk factors on the retinal vasculature.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Study Population

The Singapore Malay Eye Study is a population-based cross-sectional survey of eye diseases in urban Malay adults ranging in age from 40 to 80 years and residing in 15 districts in Southwestern Singapore. Subjects were selected, using an age-stratified (by 10-year age group) random sampling method, from a computer-generated list provided by the Singapore Ministry of Home Affairs. Of 4168 eligible persons, 3280 (78.7%) participated in the study from August 2004 to June 2006. The methodology and

Results

Retinal photographs were available in 3266 of 3280 subjects. We excluded eyes with poor image quality (n=154), eyes without at least 6 large gradable arterioles or venules (n=159), images without an adequate measured area (optical artifact) at measured zone (n=24), and retinal images with the wrong camera setting (n=14), leaving 2915 subjects for the final analysis (88.9% of 3280 participants). The mean (standard deviation) age of participants was 57.7 (10.7) years, systolic blood pressure was

Discussion

We reported on the distributions of retinal arteriolar and venular tortuosity, measured quantitatively from fundus images by a computer-assisted program, in a general adult population of persons aged 40 to 80 years. We showed that retinal vascular tortuosity measurements were reliable, and that retinal vascular tortuosity alterations were significantly and independently associated with age, blood pressure, and other CVD risk factors.

By using our new computer-assisted method, we demonstrated

References (36)

T.Y. Wong et al.
The eye in hypertension
Lancet
(2007)
T.Y. Wong et al.
Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study
Lancet
(2001)
T.Y. Wong et al.
Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality
Surv Ophthalmol
(2001)
R.I. Lindley et al.
Retinal microvasculature in acute lacunar stroke: a cross-sectional study
Lancet Neurol
(2009)
T.Y. Wong et al.
The prevalence and risk factors of retinal microvascular abnormalities in older persons: the Cardiovascular Health Study
Ophthalmology
(2003)
K. McGeechan et al.
Risk prediction of coronary heart disease based on retinal vascular caliber (from the Atherosclerosis Risk In Communities [ARIC] Study)
Am J Cardiol
(2008)
J.S. Wolffsohn et al.
Improving the description of the retinal vasculature and patient history taking for monitoring systemic hypertension
Ophthalmic Physiol Opt
(2001)
M.I. Boone et al.
Increased retinal vascular tortuosity in gestational diabetes mellitus
Ophthalmology
(1989)
D.C. Ferrara et al.
Early bevacizumab treatment of central retinal vein occlusion
Am J Ophthalmol
(2007)
W.E. Hart et al.
Measurement and classification of retinal vascular tortuosity
Int J Med Inform
(1999)

L.D. Hubbard et al.

Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study

Ophthalmology

(1999)

D.J. Couper et al.

Reliability of retinal photography in the assessment of retinal microvascular characteristics: the Atherosclerosis Risk in Communities Study

Am J Ophthalmol

(2002)

T.Y. Wong et al.

Hypertensive retinopathy

N Engl J Med

(2004)

T.Y. Wong et al.

Retinal arteriolar narrowing and risk of coronary heart disease in men and women: the Atherosclerosis Risk in Communities Study

JAMA

(2002)

T.Y. Wong et al.

Cerebral white matter lesions, retinopathy, and incident clinical stroke

JAMA

(2002)

J.J. Wang et al.

Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations

Eur Heart J

(2007)

M.K. Ikram et al.

Retinal vessel diameters and risk of stroke: the Rotterdam Study

Neurology

(2006)

S.R. Daniels et al.

Determinants of retinal vascular abnormalities in children and adolescents with essential hypertension

J Hum Hypertens

(1993)

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In a pilot study, vasculature was manually segmented on flat-mount images of OIR and normoxic (NOX) mice retinas and segmentations were analyzed with iROP-Assist to quantify vascular tortuosity metrics. In a large cohort of age-matched (postnatal day 12 [P12], P17, P25) NOX and OIR mice retinas, NV, VO, and vascular tortuosity were quantified and compared. In a third experiment, vascular tortuosity in OIR mice retinas was quantified on P17 following intravitreal injection with anti-VEGF (aflibercept) or Immunoglobulin G isotype control on P12.
Vascular tortuosity.
Cumulative tortuosity index was the best metric produced by iROP-Assist for discriminating between OIR mice and NOX controls. Increased vascular tortuosity correlated with disease activity in OIR. Treatment of OIR mice with aflibercept rescued vascular tortuosity.
Vascular tortuosity is a quantifiable feature of the OIR model that correlates with disease severity and may be quickly and accurately quantified using the iROP-Assist algorithm.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Hypertensive Retinopathy (HR) is a retinal disease caused by elevated blood pressure for a prolonged period. There are no obvious signs in the early stages of high blood pressure, but it affects various body parts over time, including the eyes. HR is a biomarker for several illnesses, including retinal diseases, atherosclerosis, strokes, kidney disease, and cardiovascular risks. Early microcirculation abnormalities in chronic diseases can be diagnosed through retinal examination prior to the onset of major clinical consequences. Computer-aided diagnosis (CAD) plays a vital role in the early identification of HR with improved diagnostic accuracy, which is time-efficient and demands fewer resources. Recently, numerous studies have been reported on the automatic identification of HR. This paper provides a comprehensive review of the automated tasks of Artery-Vein (A/V) classification, Arteriovenous ratio (AVR) computation, HR detection (Binary classification), and HR severity grading. The review is conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The paper discusses the clinical features of HR, the availability of datasets, existing methods used for A/V classification, AVR computation, HR detection, and severity grading, and performance evaluation metrics. The reviewed articles are summarized with classifiers details, adoption of different kinds of methodologies, performance comparisons, datasets details, their pros and cons, and computational platform. For each task, a summary and critical in-depth analysis are provided, as well as common research issues and challenges in the existing studies. Finally, the paper proposes future research directions to overcome challenges associated with data set availability, HR detection, and severity grading.
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Hypertensive Retinopathy (HR) is a retinal manifestation caused due to persistently raised blood pressure. Computer-aided diagnosis (CAD) plays an important role in the early identification of HR with high diagnostic accuracy, which is time-efficient and demands fewer resources. At present, there are very few computerized systems available for HR detection. Nonetheless, because of the limited number of datasets, there is still room for significant advancement in HR detection. Recently, deep learning has drawn a lot of interest, mainly due to its efficiency has been significantly enhanced. In this work, we develop a novel approach for HR detection based on few-shot learning using a pretrained initial baseline model in which transferable knowledge is obtained for feature embedding on few-shot prediction (limited number of images). It is used to avoid overfitting and to improve generalization on smaller datasets. The proposed baseline model consists of a CNN and LSTM-based HR detection model that can recognize base categories and dynamically generate classification weight vectors for few-shot datasets. The pretrained baseline classifier maximizes the reuse of feature embedding on few-shot datasets, which is comparatively more suitable for smaller datasets than other deep-learning models. In addition, the similarity-based cosine distance classifier followed by the softmax function is used for a few-shot dataset classification. Our experimental findings indicate the effectiveness of the proposed method in HR detection, evaluated on publicly available datasets (including recently released datasets). Therefore, the proposed system can effectively detect HR and can be used by clinicians for referral as well as to facilitate mass screening.
Genome-wide Association Studies of Retinal Vessel Tortuosity Identify Numerous Novel Loci Revealing Genes and Pathways Associated With Ocular and Cardiometabolic Diseases
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To identify novel susceptibility loci for retinal vascular tortuosity, to better understand the molecular mechanisms modulating this trait, and reveal causal relationships with diseases and their risk factors.
Genome-wide Association Studies (GWAS) of vascular tortuosity of retinal arteries and veins followed by replication meta-analysis and Mendelian randomization (MR).
We analyzed 116 639 fundus images of suitable quality from 63 662 participants from 3 cohorts, namely the UK Biobank (n = 62 751), the Swiss Kidney Project on Genes in Hypertension (n = 397), and OphtalmoLaus (n = 512).
Using a fully automated retina image processing pipeline to annotate vessels and a deep learning algorithm to determine the vessel type, we computed the median arterial, venous and combined vessel tortuosity measured by the distance factor (the length of a vessel segment over its chord length), as well as by 6 alternative measures that integrate over vessel curvature. We then performed the largest GWAS of these traits to date and assessed gene set enrichment using the novel high-precision statistical method PascalX.
We evaluated the genetic association of retinal tortuosity, measured by the distance factor.
Higher retinal tortuosity was significantly associated with higher incidence of angina, myocardial infarction, stroke, deep vein thrombosis, and hypertension. We identified 175 significantly associated genetic loci in the UK Biobank; 173 of these were novel and 4 replicated in our second, much smaller, metacohort. We estimated heritability at ∼25% using linkage disequilibrium score regression. Vessel type specific GWAS revealed 116 loci for arteries and 63 for veins. Genes with significant association signals included COL4A2, ACTN4, LGALS4, LGALS7, LGALS7B, TNS1, MAP4K1, EIF3K, CAPN12, ECH1, and SYNPO2. These tortuosity genes were overexpressed in arteries and heart muscle and linked to pathways related to the structural properties of the vasculature. We demonstrated that retinal tortuosity loci served pleiotropic functions as cardiometabolic disease variants and risk factors. Concordantly, MR revealed causal effects between tortuosity, body mass index, and low-density lipoprotein.
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: Manuscript no. 2010-606.

: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: Funding: National Medical Research Council 0796/2003, and STaR/0003/2008 Singapore Bio Imaging Consortium Grant C-011/2006.

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Original articleRetinal Vascular Tortuosity, Blood Pressure, and Cardiovascular Risk Factors

Objective

Design

Participants

Methods

Mean Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Study Population

Results

Discussion

Lancet

Lancet

Surv Ophthalmol

Lancet Neurol

Ophthalmology

Am J Cardiol

Ophthalmic Physiol Opt

Ophthalmology

Am J Ophthalmol

Int J Med Inform

Ophthalmology

Am J Ophthalmol

Hypertensive retinopathy

N Engl J Med

Retinal arteriolar narrowing and risk of coronary heart disease in men and women: the Atherosclerosis Risk in Communities Study

JAMA

Cerebral white matter lesions, retinopathy, and incident clinical stroke

JAMA

Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations

Eur Heart J

Retinal vessel diameters and risk of stroke: the Rotterdam Study

Neurology

Determinants of retinal vascular abnormalities in children and adolescents with essential hypertension

J Hum Hypertens

Original article
Retinal Vascular Tortuosity, Blood Pressure, and Cardiovascular Risk Factors