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      Retinal Vascular Caliber Measurements: Clinical Significance, Current Knowledge and Future Perspectives

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          Abstract

          The retinal vasculature provides a unique window to assess vascular health noninvasively and directly in vivo. Advances in fundus photography and retinal image analysis techniques have enabled the objective and accurate assessment of quantitative retinal vascular caliber measurement. Over the last decade, large population-based studies have shown that retinal vascular calibers are associated with a wide range of subclinical (e.g. atherosclerosis, inflammation and endothelial dysfunction) and clinical cardiovascular diseases (hypertension, diabetes mellitus, stroke, kidney and heart diseases). However, while retinal image analysis provided exciting possibilities to study the pathogenesis of these diseases, its direct applicability in a clinical setting as a ‘test' to predict cardiovascular diseases is yet to be established, particularly within the context of being used as a population screening tool. Nevertheless, with continual development of retinal imaging techniques and newer understanding of the clinical significance of these retinal changes, there remains scope for the development of retinal vascular caliber measurements as a biomarker for vascular disease risk assessment in targeted areas and patient subgroups (e.g. patients with diabetes, suspected hypertension and stroke).

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          Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

          Eileen Lim, A Veves, Paul King … (1999)
          Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.
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            Relationship of retinal vascular caliber with diabetes and retinopathy: the Multi-Ethnic Study of Atherosclerosis (MESA).

            Jie Jin Wang, Christine Nguyen, Ronald Klein … (2008)
            To examine the relationship of retinal vascular caliber with diabetes, glycemia, and diabetic retinopathy. Population-based study using data from the Multi-Ethnic Study of Atherosclerosis (MESA), comprising 5,976 individuals (whites, blacks, Hispanics, and Chinese) residing in six U.S. communities who were free of clinical cardiovascular disease at baseline. Retinal vascular caliber was measured from digital retinal photographs. There were 4,585 individuals with normal fasting glucose (NFG), 499 with impaired fasting glucose (IFG), 165 with diabetes with retinopathy signs, and 727 with diabetes without retinopathy signs. After multivariate analysis, retinal arteriolar caliber increased from 143.8 microm in subjects with NFG to 144.5 microm in IFG and 146.1 microm in diabetes (P < 0.001 for trend). Retinal venular caliber increased from 214.4 microm in NFG to 216.7 microm in IFG and 218.0 microm in diabetes (P < 0.001 for trend). Retinal venular caliber was significantly larger with increasing levels of fasting glucose and A1C. In a subgroup analysis by ethnicity, the association between wider arteriolar caliber and diabetes was evident in whites only, whereas wider venular caliber and diabetes was evident in Hispanics and Chinese only. In people with diabetes, eyes with retinopathy had larger retinal venular but not arteriolar caliber. Retinal arteriolar and venular calibers are larger in individuals with diabetes, but the pattern of associations appears to vary by ethnicity. Retinal venular caliber is additionally associated with retinopathy signs. These findings add further to the concept that variations in retinal vascular caliber may reflect early diabetic microvascular damage.
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              Obesity and eye diseases.

              Ning Cheung, Tien Wong (2015)
              The prevalence of obesity has reached epidemic proportions in many countries. Although its impact on overall health is well documented, less is known about the ocular manifestations of obesity. Among different eye diseases, obesity has been linked with age-related cataract, glaucoma, age-related maculopathy, and diabetic retinopathy. Numerous population-based and prospective studies support an association between obesity and risk of age-related cataract. However, the nature and strength of these associations, particularly with the different cataract subtypes, remains to be determined. There is strong evidence that obesity is associated with elevated intraocular pressure, but there is no convincing data to support a more direct association between obesity and glaucomatous optic neuropathy. Studies to date have not found a consistent pattern of association between obesity and risk of age-related maculopathy or diabetic retinopathy. Thus, although obesity may be a risk factor for many ocular conditions, the present literature is inadequate to establish any convincing associations. Furthermore, whether weight loss reduces the risk of eye diseases remains unresolved. Because of the potential public health impact of obesity, there is a greater need to understand its ocular effects.
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                Author and article information

                Journal
                Journal ID (publisher-id): OPH
                Journal ID (nlm-ta): Ophthalmologica
                Journal ID (doi): 10.1159/issn.0030-3755
                Title: Ophthalmologica
                Publisher: S. Karger AG
                ISSN (Print): 0030-3755
                ISSN (Electronic): 1423-0267
                Publication date Subscription-year: 2013
                Publication date (Print): April 2013
                Publication date (Electronic): 20 September 2012
                Volume: 229
                Issue: 3
                Pages: 125-136
                Affiliations
                aDepartment of Ophthalmology, Yong Loo Lin School of Medicine and bSaw Swee Hock School of Public Health, National University of Singapore, cSingapore Eye Research Institute, Singapore National Eye Centre, and dCentre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore; eDepartments of Epidemiology and Ophthalmology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
                Author notes
                *M.K. Ikram, MD, PhD, Department of Ophthalmology, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore 119228 (Singapore), Tel. +65 8126 1594, E-Mail kamran_ikram@nuhs.edu.sg
                Article
                Publisher ID: 342158 Other ID: Ophthalmologica 2013;229:125-136
                DOI: 10.1159/000342158
                PubMed ID: 23006932
                SO-VID: 89f0a122-eaf2-4b2e-920a-fd73bcde9bc4
                Copyright © © 2012 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 29 June 2012
                Date accepted : 30 June 2012
                Page count
                Tables: 1, Pages: 12
                Categories
                Subject: EURETINA - Review

                ScienceOpen disciplines: Vision sciences,Ophthalmology & Optometry,Pathology
                Keywords: Cardiovascular diseases,Retinal image analysis,Retinal vascular caliber measurement
                Data availability:
                ScienceOpen disciplines: Vision sciences, Ophthalmology & Optometry, Pathology
                Keywords: Cardiovascular diseases, Retinal image analysis, Retinal vascular caliber measurement

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