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      Retinal vascular tortuosity assessment: inter-intra expert analysis and correlation with computational measurements

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          Abstract

          Background

          The retinal vascular tortuosity can be a potential indicator of relevant vascular and non-vascular diseases. However, the lack of a precise and standard guide for the tortuosity evaluation hinders its use for diagnostic and treatment purposes. This work aims to advance in the standardization of the retinal vascular tortuosity as a clinical biomarker with diagnostic potential, allowing, thereby, the validation of objective computational measurements on the basis of the entire spectrum of the expert knowledge.

          Methods

          This paper describes a multi-expert validation process of the computational vascular tortuosity measurements of reference. A group of five experts, covering the different clinical profiles of an ophthalmological service, and a four-grade scale from non-tortuous to severe tortuosity as well as non-tortuous / tortuous and asymptomatic / symptomatic binary classifications are considered for the analysis of the the multi-expert validation procedure. The specialists rating process comprises two rounds involving all the experts and a joint round to establish consensual rates. The expert agreement is analyzed throughout the rating procedure and, then, the consensual rates are set as the reference to validate the prognostic performance of four computational tortuosity metrics of reference.

          Results

          The Kappa indexes for the intra-rater agreement analysis were obtained between 0.35 and 0.83 whereas for the inter-rater agreement in the asymptomatic / symptomatic classification were between 0.22 and 0.76. The Area Under the Curve (AUC) for each expert against the consensual rates were placed between 0.61 and 0.83 whereas the prognostic performance of the best objective tortuosity metric was 0.80.

          Conclusions

          There is a high inter and intra-rater variability, especially for the case of the four grade scale. The prognostic performance of the tortuosity measurements is close to the experts’ performance, especially for Grisan measurement. However, there is a gap between the automatic effectiveness and the expert perception given the lack of clinical criteria in the computational measurements.

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          Most cited references23

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          A fast parallel algorithm for thinning digital patterns

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            Twisted Blood Vessels: Symptoms, Etiology and Biomechanical Mechanisms

            Tortuous arteries and veins are commonly observed in humans and animals. While mild tortuosity is asymptomatic, severe tortuosity can lead to ischemic attack in distal organs. Clinical observations have linked tortuous arteries and veins with aging, atherosclerosis, hypertension, genetic defects and diabetes mellitus. However, the mechanisms of their formation and development are poorly understood. This review summarizes the current clinical and biomechanical studies on the initiation, development and treatment of tortuous blood vessels. We submit a new hypothesis that mechanical instability and remodeling could be mechanisms for the initiation and development of these tortuous vessels.
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              Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke.

              Abnormalities of the retinal microcirculation are found in hypertension and diabetes and predict cardiovascular mortality. This study examined the relationship between abnormalities of the retinal microvasculature and death from ischemic heart disease (IHD) and stroke. A population-based, nested case-control study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years) who died of IHD (n=126) or stroke (n=28) over a 10-year period were age and gender matched with controls subjects (n=528; case:control matching, approximately 1:4). Retinal photographs of cases and controls were digitized and analyzed using a computer-based technique. Increased risk of IHD death was associated with a suboptimal relationship of arteriolar diameters at bifurcation (P=0.02 unadjusted) and decreased retinal arteriolar tortuosity (P=0.011 unadjusted). These associations remained significant after adjustment for age, sex, past history of cardiovascular disease, and other known cardiovascular risk factors. Increased arteriolar length:diameter ratio, a measure of generalized arteriolar narrowing, was associated with increased stroke mortality (P=0.02 unadjusted). This association was independent of age and gender but was attenuated by adjustment for systolic blood pressure (P=0.15). Other quantitative measures of the retinal microvascular network (eg, venular tortuosity and arteriolar and venular bifurcation angle) were not associated with death from IHD or stroke. Retinal microvascular abnormalities are predictive of death from IHD and stroke. A detailed assessment of the retinal microvascular network from digitized photographs may be useful in the noninvasive assessment of target organ damage and cardiovascular risk.
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                Author and article information

                Contributors
                l.ramos@udc.es
                j.novo@udc.es
                jose.rouco@udc.es
                stephanie.romeo.villadoniga@sergas.es
                Maria.Dolores.Alvarez.Diaz@sergas.es
                mortega@udc.es
                Journal
                BMC Med Res Methodol
                BMC Med Res Methodol
                BMC Medical Research Methodology
                BioMed Central (London )
                1471-2288
                20 November 2018
                20 November 2018
                2018
                : 18
                : 144
                Affiliations
                [1 ]ISNI 0000 0001 2176 8535, GRID grid.8073.c, University of A Coruña, Department of Computer Science, ; Campus de Elviña, A Coruña, 15071 Spain
                [2 ]ISNI 0000 0001 2176 8535, GRID grid.8073.c, CITIC-Research Center of Information and Communication Technologies, University of A Coruña, ; A Coruña, Spain
                [3 ]ISNI 0000 0004 1771 0279, GRID grid.411066.4, Servizo de Oftalmoloxía, Complexo Hospitalario Universitario de Ferrol, ; Ferrol, A coruña, Spain
                Article
                598
                10.1186/s12874-018-0598-3
                6245828
                30458717
                b198b8ff-f56f-4e2d-88eb-c43aceca757b
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 May 2018
                : 30 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI14/02161, DTS15/00153
                Funded by: FundRef http://dx.doi.org/10.13039/501100008530, European Regional Development Fund;
                Award ID: PI14/02161, DTS15/00153, DPI2015-69948-R, ED431G/01, ED431C 2016-047
                Funded by: FundRef http://dx.doi.org/10.13039/501100003329, Ministerio de Economía y Competitividad;
                Award ID: DPI2015-69948-R
                Funded by: FundRef http://dx.doi.org/10.13039/501100008425, Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia;
                Award ID: ED431G/01, ED431C 2016-047
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Medicine
                retinal circulation,vascular tortuosity,fundus images,computer-aided diagnosis,image analysis

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