diagnostics

Review
Automated Systems for Calculating Arteriovenous Ratio in
Retinographies: A Scoping Review
Rosa García-Sierra 1,2,3,4 , Victor M. López-Lifante 1,5, * , Erik Isusquiza Garcia 6 , Antonio Heras 1,7 ,
Idoia Besada 6 , David Verde Lopez 8 , Maria Teresa Alzamora 1,7 , Rosa Forés 1 , Pilar Montero-Alia 1 ,
Jurgi Ugarte Anduaga 6 and Pere Torán-Monserrat 1,2,4,9

1 Research Support Unit Metropolitana Nord, Primary Care Research Institut Jordi Gol (IDIAPJGol),
08303 Mataró, Spain
2 Multidisciplinary Research Group in Health and Society GREMSAS (2017 SGR 917), 08007 Barcelona, Spain
3 Nursing Department, Faculty of Medicine, Universitat Autònoma de Barcelona, Campus Bellaterra,
08193 Barcelona, Spain
4 Primary Care Group, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain
5 Palau-solità i Plegamans Primary Healthcare Centre, Palau-solità i Plegamans, Gerència d’Àmbit d’Atenció
Primària Metropolitana Nord, Institut Català de la Salut, 08184 Barcelona, Spain
6 ULMA Medical Technologies, S. Coop, 20560 Onati, Spain
7 Primary Healthcare Centre Riu Nord-Riu Sud, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord,
Institut Català de la Salut, Santa Coloma de Gramenet, 08921 Barcelona, Spain
8 Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), 08007 Barcelona, Spain
9 Department of Medicine, Faculty of Medicine, Universitat de Girona, 17004 Girona, Spain
* Correspondence: vmlopezli.mn.ics@gencat.cat
Citation: García-Sierra, R.;
López-Lifante, V.M.; Isusquiza
Abstract: There is evidence of an association between hypertension and retinal arteriolar narrowing.
Garcia, E.; Heras, A.; Besada, I.; Verde
Manual measurement of retinal vessels comes with additional variability, which can be eliminated
Lopez, D.; Alzamora, M.T.; Forés, R.;
using automated software. This scoping review aims to summarize research on automated retinal
Montero-Alia, P.; Ugarte Anduaga, J.;
et al. Automated Systems for
vessel analysis systems. Searches were performed on Medline, Scopus, and Cochrane to find studies
Calculating Arteriovenous Ratio in examining automated systems for the diagnosis of retinal vascular alterations caused by hyperten-
Retinographies: A Scoping Review. sion using the following keywords: diagnosis; diagnostic screening programs; image processing,
Diagnostics 2022, 12, 2865. computer-assisted; artificial intelligence; electronic data processing; hypertensive retinopathy; hy-
https://doi.org/10.3390/ pertension; retinal vessels; arteriovenous ratio and retinal image analysis. The searches generated
diagnostics12112865 433 articles. Of these, 25 articles published from 2010 to 2022 were included in the review. The
Academic Editors: Mario Damiano
retinographies analyzed were extracted from international databases and real scenarios. Automated
Toro, Daniele Tognetto and Rosa systems to detect alterations in the retinal vasculature are being introduced into clinical practice for
Giglio diagnosis in ophthalmology and other medical specialties due to the association of such changes with
various diseases. These systems make the classification of hypertensive retinopathy and cardiovascu-
Received: 2 October 2022
lar risk more reliable. They also make it possible for diagnosis to be performed in primary care, thus
Accepted: 14 November 2022
optimizing ophthalmological visits.
Published: 18 November 2022

Publisher’s Note: MDPI stays neutral Keywords: image processing; computer assisted; retinal vessels; retinal image analysis; diagnosis;
with regard to jurisdictional claims in hypertensive retinopathy; diagnostic screening programs
published maps and institutional affil-
iations.

1. Introduction
Copyright: © 2022 by the authors. Fundus photography, also known as retinography, is a popular imaging technique
Licensee MDPI, Basel, Switzerland. used to visualize changes in the retinal vessels through the pupil. It can capture changes in
This article is an open access article vascular caliber and the global geometric patterns of the retina [1]. It is also able to detect
distributed under the terms and signs of retinopathy—such as microaneurysms, hemorrhages, cotton wool spots and hard
conditions of the Creative Commons exudates, and symptoms of the retinal arteriolar wall (e.g., generalized and focal arteriolar
Attribution (CC BY) license (https:// narrowing and arteriovenous nicking)—all of which are often observed in patients with
creativecommons.org/licenses/by/ systemic diseases, such as diabetes and hypertension.
4.0/).

Diagnostics 2022, 12, 2865. https://doi.org/10.3390/diagnostics12112865 https://www.mdpi.com/journal/diagnostics

Diagnostics 2022, 12, 2865 2 of 14

Regarding diabetes, the 1989 Saint Vincent Declaration set the goal of reducing
diabetes-related blindness by one-third over the next five years. This was restated in
the 2005 Liverpool Declaration’s objective of establishing systematic screening programs
to reach at least 80% of the population with diabetes by 2021 [2]. The increased demand
for diabetic retinopathy (DR) screening resulting from systematic programs could be met
using automated retinal image analysis systems. Such systems can be used in different DR
screening scenarios and offer relatively high sensitivity and a substantial reduction in the
workload of the health system. Moreover, they are now mature enough to be safely used in
DR screening [3,4]. Automated tools improve the quality of DR screening and accessibility
to medical care while reducing the cost of the disease by promoting early detection and
treatment, which is essential to stop progression [5].
Regarding hypertension, there is evidence that it is associated with retinal arteri-
olar narrowing. Retinal vessel diameter is expressed as arteriovenous ratio (AVR). Ac-
cording to the Keith–Wagener–Barker classification, AVR values of less than 0.66 reflect
hypertensive retinopathy [6].
Arteriolar narrowing is associated with more severe coronary heart disease, stroke,
and mortality [6–9]. There has also been a recent increase in evidence showing that retinal
arteriolar narrowing, retinal venular widening, and a suboptimal retinal vascular network
are associated with poorer cognitive performance [10–12]. Retinal imaging techniques
provide unique information about the state of the microvasculature and neuronal structure,
different from current neuroimaging markers, such as brain magnetic resonance imaging
(MRI), and systemic markers, such as blood pressure. While retinal imaging cannot fully
replace PET scans or MRIs in the diagnosis of disease, it does offer a complementary
approach to these brain imaging techniques and has considerable potential in clinical and
research settings [13].
For all these reasons, retinal imaging can be used as a risk stratification tool because
studies suggest that the addition of retinal measures improves the prediction of stroke
(an improvement on established risk factors of approximately 10%) [14,15]. Although just
a modest improvement in prediction, these findings suggest that adding a combination
of various retinal features and/or retinal functional parameters (i.e., a “multimarker ap-
proach”) may further improve the prediction of dementia and stroke. It might also enable
the identification of a more specific subgroup of patients who could benefit from more
intensive and expensive examinations, such as brain MRI.
Retinal vascular imaging has also been used to examine the effects of antihypertensive
therapy, showing that lowering blood pressure leads to the regression of retinal vascular
signs [16,17]. While there have been no significant intervention studies using changes in
retinal images as alternative outcome measurements in dementia and stroke, this approach
has substantial potential. In addition to its clinical value, retinal imaging may also be
a worthwhile research tool in major brain and neurological diseases, such as multiple
sclerosis [18–20], depression [21,22], and schizophrenia [23,24].
Evaluating retinographies manually implies additional variability in retinal vessel
measurements, even when following a standardized protocol. This variability is eliminated
if fully automated software is used to measure retinal vascular caliber and other anomalies,
although there may be other additional sources of variation in the measurements, such as
retinal pigmentation, pupil dilation, the presence of cataracts and other media opacities,
photographic technique, type of camera (mydriatic/non-mydriatic or desktop/portable),
and image quality (brightness, focus, and contrast) [25]. Manually segmenting vessels,
labeling arteries and veins, and localizing the optic disc is a time-consuming task that
decreases process efficiency. However, over the past two decades, multiple software
systems have been developed to measure and semi-automatically assess the retinal vessel
caliber from fundus photographs using artificial intelligence (AI) algorithms [26].
Research question: What is the current stage of implementation of automated retinal
vessel analysis systems retinographies?
Diagnostics 2022, 12, 2865 3 of 14

Aim: This scoping review aims to summarize the research available on automated
retinal vessel measurement systems so they may be considered in future research and
introduced into clinical practice.

2. Materials and Methods

This review followed the PRISMA extension checklist for scoping reviews [27].

2.1. Search Strategy, Data Sources, and Selection

Searches were performed in the Medline, Scopus, and Cochrane electronic databases
to locate studies published between 1 january 2004 and 1 september 2022 examining au-
tomated systems for the diagnosis of retinal vessel alterations caused by hypertension.
The following keywords were used: diagnosis; diagnostic screening programs; image pro-
cessing, computer-assisted; artificial intelligence; electronic data processing; hypertensive
retinopathy; hypertension; retinal vessels; arteriovenous ratio (no MeSH); retinal image
analysis (no MeSH).

2.2. Selection Criteria

Articles were included in the review if they met the following inclusion criteria:
(1) Automated systems were used to partially or totally analyze photographic images of
the retina.
(2) Changes in the retinal vascular network and/or retinal vascular measurements
were analyzed.
(3) The publication was peer-reviewed.
(4) The study was observational, descriptive (population, cross-sectional), analytical
(case studies and controls, cohorts), experimental (clinical trials), or a validation of
experiments/new image analysis methods.
Only papers written in English were selected. Studies using automated systems for
diabetes screening were excluded. Qualitative studies and gray literature were excluded.

2.3. Selection of Studies

Abstracts and articles were independently reviewed by two members of the research
team based on predetermined inclusion and exclusion criteria. When it was unclear whether
an article should be included or some discrepancy appeared, the coordinating researcher of
the study also reviewed it.

2.4. Data Extraction

Initial data extraction elements included: author, country, research aim, study de-
sign, study setting, interpretation system, degree of software automation (semi-automatic,
automatic), lesions that the system was able to detect, focus of the photograph and area
analyzed, sensitivity, specificity, diagnostic precision, economic evaluation, time savings,
local management or the possibility of electronically sending the image to a repository,
possibility of comparison for patient follow-up.
Data from each article were independently extracted by two of the authors and then
verified by two others.

3. Results
3.1. Search Process
The PRISMA flow diagram (Figure 1) describes the steps taken to select the articles [28].
The search strategies generated 433 articles, of which 58 full-length articles were evaluated
for eligibility. Of these, 25 articles were included in the scoping review.
 The PRISMA flow diagram (Figure 1) describes the steps taken to select the article
[28]. The search strategies generated 433 articles, of which 58 full-length articles were eva
Diagnostics uated for eligibility. Of these, 25 articles were included in the scoping review.4 of 14
2022, 12, 2865

Figure 1. PRISMA 2020 flow diagram.

3.2. Characteristics of the Articles

Figure 1. PRISMA 2020 flow diagram.
The articles included in the review were published between 2010 and 2022, and the
number of retinographies analyzed ranged from 20 to 95,716. These retinographies were
3.2. Characteristics of thebyArticles
provided international databases, as well as real scenarios. Table 1 presents a summary
of the characteristics of the studies, including first author, year of publication, the country
The articles included
where the studyin the
was reviewstudy
conducted, wereaim,published
sample, numberbetween 2010 and
of retinographies, name2022,
of the and th
number of retinographies
software used, analyzed rangedand,
degree of automation, from 20the
lastly, toscenario
95,716.in These
which it retinographies
was tested. wer
The median number of retinographies analyzed in the included
provided by international databases, as well as real scenarios. Table 1 presents a summar studies was 180, with
a maximum of 54,714 and a minimum of 40. In relation to the degree of automation, in
of the characteristics of they
10 articles the used
studies, including
automatic firstinauthor,
software and year of systems.
15 semi-automated publication, the countr
where the study was conducted, study aim, sample, number of retinographies, name o
3.3. Interpretation Procedures
the software used, degree of automation, and, lastly, the scenario in which it was tested
The analysis systems included in these articles detect various alterations of the vessels,
The median number
including of retinographies
tortuosity, analyzed
arteriolar and venular in the
caliber, and even included studies
AVR calculation. Table 2was
shows180, wit
a description of the retinal lesions detected in each study, the focus
a maximum of 54,714 and a minimum of 40. In relation to the degree of automation, in 1 of the photograph, and
the area of the retina that was analyzed. The focus of the image was mainly on the macula
articles they used
andautomatic
optic disc, andsoftware
the analyzed and
areain 15 semi-automated
ranged systems.
between 2 to 3 radii from the optic disc.

3.3. Interpretation Procedures

The analysis systems included in these articles detect various alterations of the ves
sels, including tortuosity, arteriolar and venular caliber, and even AVR calculation. Tabl
Diagnostics 2022, 12, 2865 5 of 14

Table 1. Characteristics of the studies.

Author, Year Country Aim Sample Photographs Software Automation Type Scenario
Measure arteriovenous relationship
Pakistan and United and degree of retinal vessel
Badawi, 2022 [29] 504 504 VAMPIRE a Automated RVM dataset b
Arab Emirates tortuosity to detect and classify
hypertensive retinopathy.
Assess the association between
cumulative blood pressure,
Huang, 2022 [30] China 1818 Semi-automated ARIC c
averaged over 25 years, and retinal
vessel calibers.
Method for the differentiation and
classification of retinal vessels by Real scenario
Irshad, 2021 [31] Australia 142 BPSO Automated
Binary Particle Swarm Optimization INSPIRE-AVR VICAVR
(BPSO).
Report on the construction of a
model to further explore the CNN 8 DRIVE 1
Dai, 2020 [32] China 1419 2012 Automated
pathophysiological changes of the architecture STARE 2
retinal microvasculature.
Assess the relevance of a retinal
Maderuelo-Fernandez,
Spain vessel analysis system in target 250 495 ALTAIR d Semi-automated Real scenario
2020 [26]
organ damage and vascular risk.
Evaluate whether retinal vessel
Robertson,
UK measurements were associated 440 880 VAMPIRE a Semi-automated NICOLA 3
2020 [33]
with hypertension.
Examine the association between
United Kingdom
Tapp, 2019 [34] UK retinal vessel morphometry and 54,714 95,716 QUARTZ e Automated
Biobank
blood pressure and arterial stiffness.
Determine whether a high burden of
white matter hyperintensities can be CU-RISK
Lau, 2019 [35] Hong Kong 180 180 ARIA f Automated
detected through images of COHORT 4
the retina.
Examine the association between
blood pressure measurements and Real scenario
He, 2018 [36] China 1501 1501 IVAN g Semi-automated
changes in the retinal Pediatrics
microvasculature.
Assess retinal vessel diameter as a
Adiarti, 2018 [37] Indonesia 54 108 SIVA h Semi-automated Real scenario
marker of glaucoma.
Assess AVR calculation as a classifier
INSPIRE-AVR 5
Akbar, 2018 [38] Pakistan of the degree of arterial 100 198 - Automated
VICAVRAVRDB 6
hypertension.
Diagnostics 2022, 12, 2865 6 of 14

Table 1. Cont.

Author, Year Country Aim Sample Photographs Software Automation Type Scenario
Compare a new method of retinal
Iwase, 2017 [39] Japan vessel measurement with the 99 180 - Semi-automated Real scenario
IVAN system.
Describe the associations between
Yip, 2017 [11] Singapore retinal vascular parameters and 1256 2512 SIVA h Semi-automated Real scenario
chronic kidney disease.
Investigate the association between
poor glycemic control and Real scenario
Li, 2017 [40] Singapore 55 110 SIVA jh Semi-automated
subsequent changes in the retinal Pediatrics
microvasculature.
Evaluate the usefulness of
Vázquez
Spain measuring arteriovenous ratio to 768 2262 VesselMap2 Semi-automated Real scenario
Dorrego, 2016 [41]
detect silent brain ischemia.
Cioran and
Cavallari, Develop a semi-automated method
USA, Italy 54 108 BRetina Semi-automated Real scenario
2015 [42] to assess retinal vessel morphology.
plugins
DRIVE 1
Present a fully automated software e STARE 2
Fraz, 2015 [43] Pakistan and UK - 16,000 QUARTZ Automated
to analyze the retinal vasculature. INSPIRE 5 CHASE-DB1
DIARETDB1 7
Develop a semi-automated method
DRIVE 1
Estrada, 2015 [44] USA to distinguish arteries from veins in 110 130 - Semi-automated
INSPIRE 5 WIDE
fundus images.
Identify the association between
baseline retinal vascular caliber and
Moradi, 2014 [45] USA 84 25 IVAN g Semi-automated Real scenario
visual outcome of patients with
diabetic macular edema.
Present an automated retinal vessel
Franklin, 2014 [46] India 40 40 ANN 9 Automated DRIVE 1
segmentation technique.
Develop an automatic approach for
Dashtbozorg, DRIVE1 INSPIRE-AVR 5
Portugal the classification of arteries and - 130 - Semi-automated
2014 [47] VICAVR
veins of the retinal vasculature.
Propose a methodology for
Vázquez, 2013 [48] Spain classifying arteries and veins in the - 100 - Semi-automated VICAVR-2
fundus vasculature.
Propose an automated
computational framework for retinal
Huang, 2012 [49] China - 40 - Automated DRIVE 1
vascular network labeling and
branch order analysis.
Diagnostics 2022, 12, 2865 7 of 14

Table 1. Cont.

Author, Year Country Aim Sample Photographs Software Automation Type Scenario
Develop a generic framework for
Ortega, 2010 [50] Spain 96 173 SIRIUS i Semi-automated Real scenario
processing retinal images.
Present a fast, efficient, and
Villalobos-Castaldi,
Mexico automatic algorithm to extract - 20 - Automated DRIVE 1
2010 [51]
vessels from retinal images.
VAMPIRE a : Vessel Assessment and Measurement Platform for Images of the REtina. RVM b: Retinal Vessel Morphometry. ARIC c: Atherosclerosis Risk in Communities. ALTAIR d:
Automatic image anaLyzer to assess reTinAl vessel calIber. QUARTZ e: Quantitative Analysis of Retinal Vessel Topology and size. ARIA f: Automated Retinal Image Analyzer (an
open-source software designed for automatic recognition and computation of retinal factors and parameters). IVAN g: Interactive Vessel Analysis, University of Wisconsin–Madison.
SIVA h: Singapore “I” Vessel Assessment. SIRIUS i: System for the Integration of Retinal Images Understanding Services. DRIVE 1: Digital Retinal Images for Vessel Extraction. STARE 2:
STructured Analysis of the Retina. NICOLA 3: Northern Ireland COhort for the Longitudinal study of Ageing. CU-RISK COHORT 4: The Chinese University of Hong Kong—Risk index
for Subclinical Brain Lesions in Hong Kong. INSPIRE-AVR 5: Iowa Normative Set for Processing Images of the REtina-ArterioVenous Ratio. AVRDB 6: local dataset Annotated dataset
for Vessel Segmentation and Calculation of Arteriovenous Ratio. DIARETDB1 7: Standard DIAbetic RETinopathy Database caliBration level 1. CNN 8: Convolutional Neural Networks.
ANN 9: Artificial Neural Networks. BPSO: Binary Particle Swarm Optimization.

Table 2. Lesions detected.

Author, Year Measurements Focus of the Image Area Analyzed S* SP ** DP *** Conclusions
2 to 3 radii from the Hybrid tool that combines AVR and tortuosity to
Badawi,
AVR Tortuosity Optic disc optic disc 95.5% - 96.8% detect and grade the severity of
2022 [29]
The entire retina hypertensive retinopathy.
High blood pressure, averaged over 25 years, and
Huang, 2 to 3 radii from the
CRAE a CRVE b AVR Optic disc - - - specifically DBP, was associated with narrower
2022 [30] optic disc
retinal vessel diameter.
92.7% Proposal of a method that offers improved retinal
Irshad, Classification of arteries 2 to 3 radii from the
Optic disc - - 94.6% vessel classification and is robust in
2021 [31] and veins optic disc
91.9% three different databases.
Changes in retinal vessel branching pattern were
60.9%
the most significant response to high blood
Subclinical The entire retinal 70.5%
Dai, 2020 [32] Macula 59.3% 63.8% pressure compared to other retinal microvascular
morphological features vasculature AUC:
biomarkers such as caliber, tortuosity, fractal
65.1%
dimension, and branching angle.
A concomitant association of retinal vessel
Maderuelo-Fernandez, Three concentric circles
CRAE a CRV b AVR Optic disc - - - measurements with other cardiovascular
2020 [26] around the optic disc
parameters and cardiovascular risk is shown.
Annular segment that Semi-automated AVR measurements on
Nasal-annular 6.5 to 8.5 radii from the
Robertson, 2020 [33] subtends 180◦ nasally to - - - ultra-widefield fundus images were associated
AVR optic disc
the optic disc with hypertension.
Arteriolar and venular The entire retinal Associations between retinal vessel morphometry,
Tapp, 2019 [34] Optic disc and macula - - -
diameter and Tortuosity vasculature blood pressure, and arterial stiffness index.
Diagnostics 2022, 12, 2865 8 of 14

Table 2. Cont.

Author, Year Measurements Focus of the Image Area Analyzed S* SP ** DP *** Conclusions
a
CRAE CRVE b Automatic retinal image analysis can detect
Arteriole occlusion 2 to 3 radii from the community-dwelling subjects who do not have
Lau, 2019 [35] Macula 93% 98% -
Hemorrhages optic disc dementia and who have a significant burden of
Tortuosity white matter hyperintensities in their brains.
Higher blood pressure was significantly associated
He, 2018 [36] CRAE a CRVE b AVR Optic disc and macula - - - with narrower retinal arterioles in a population of
12-year-olds.
Retinal arteriolar narrowing may represent
subclinical microcirculatory changes associated
Adiarti, 1 to 4 radii from the
CRAE a CRVE b AVR Optic disc and macula - - - with the presence of a glaucomatous optic disc
2018 [37] optic disc
even in the absence of increased
intraocular pressure.
Akbar, The entire retinal The system is reliable for clinical use in the
CRAE a CRVE b AVR Optic disc 98.9% 98.6% 98.8%
2018 [38] vasculature detection and grading of hypertensive retinopathy.
The method would be especially useful to
Iwase, 2 to 3 radii from the
CRAE a CRVE b AVR Optic disc - - - accurately measure retinal vessel caliber in a
2017 [39] optic disc
myopic population.
Retinal microvascular abnormalities may reflect
CRAE a CRVE b 1 to 4 radii from the early subclinical damage to the renal
Yip, 2017 [11] Optic disc - - -
Tortuosity optic disc microvasculature that is later associated with the
development of chronic kidney disease.
Pediatric patients with Type 1 diabetes and poor
CRAE a CRVE b 1 to 4 radii from the
Li, 2017 [40] Optic disc and macula - - - glycemic control showed abnormal retinal
Tortuosity optic disc
morphology in the short term.
Alteration of the retinal vasculature is associated
Vázquez Dorrego, 2 and 3 radii from the
AVR Optic disc and macula - - - with an increased risk of silent brain ischemia in
2016 [41] optic disc
hypertensive patients.
87.5% (HR) AVR, tortuosity index, and mean fractal dimension
AVR Tortuosity Mean 3.5 radii from the optic 68.8% (HR)
Cavallari, 2015 [42] Optic disc 90.9% - were altered in HR and CADASIL subjects
Fractal Dimension disc 54.5% (CADASIL)
(CADASIL) compared to age- and sex-matched control subjects.
The entire retinal Provides quantifiable measurements of retinal
Fraz, 2015 [43] AVR Tortuosity Optic disc 75.5% 98.0% 95.3%
vasculature vessel morphology.
91.0% 91.0% 90.9%
Classification of arteries The entire retinal 93.0% 94.1% 93.5% The software outputs a graph representing the
Estrada, 2015 [44] Optic disc and macula
and veins vasculature 91.7% 91.7% 91.7% retinal vasculature.
91.5% 90.2% 90.9%
Correlation between retinal venular caliber and
visual outcome in patients with diabetic macular
Moradi, CRAE a 2 and 3 radii from the
Optic disc - - - edema treated with ranibizumab. A higher CRVE,
2014 [45] CRVE b optic disc
but not CRAE, was correlated with an
improvement in vision.
Diagnostics 2022, 12, 2865 9 of 14

Table 2. Cont.

Author, Year Measurements Focus of the Image Area Analyzed S* SP ** DP *** Conclusions
The entire retinal This technique has proven to be an effective tool for
Franklin, 2014 [46] Vessel segmentation Macula - - -
vasculature blood vessel segmentation in retinal images.
The software outputs a graph representing the
Classification of arteries The entire retinal 91% 86%
Dashtbozorg, 2014 [47] Optic disc - retinal vasculature. Each segment of the retina is
and veins vasculature 90% 84%
then classified as an artery or vein.
Classification of arteries Various circumferences The best results were achieved with four separate
Vázquez, 2013 [48] Optic disc - - 87.7%
and veins around the optic disc circumferences with a value of 0.5 radii.
A useful tool to extract morphological
Huang, Skeleton of the retinal The entire retinal
Optic disc - - - characteristics in pathological studies related to
2012 [49] vascular tree vasculature
the retina.
Ortega, Various circumferences Sirius implements a web-based solution to analyze,
AVR Optic disc - - 99.2%
2010 [50] around the optic disc manage, and understand retinal images.
Villalobos-Castaldi, The entire retinal Tool to obtain an automatic threshold value to
Vessel segmentation Optic disc 96.5% 94.8% 97.6%
2010 [51] vasculature segment vessels.
S * Maximum sensitivity. SP ** Maximum specificity. DP *** Diagnostic precision. CRAE a : Central Retinal Arteriolar Equivalent. CRVE b : Central Retinal Venular Equivalent. AVR:
Arteriole–to–Venule Ratio. CADASIL: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. HR: Hypertensive Retinopathy.
Diagnostics 2022, 12, 2865 10 of 14

Lastly, the sensitivity, specificity, and diagnostic accuracy were recorded, although this
information was only reported in seven articles.
The researchers were initially interested in studying additional data, such as economic
evaluation, time savings, local management or the possibility of electronically sending the
image to a repository, and the possibility of comparison for patient follow-up. However, the
articles selected did not provide this information; therefore, such data were not collected.

3.4. Summary of the Results

Most of the articles reviewed fall into two main categories. The first includes publi-
cations dealing with automated or semi-automated systems that measure retinal vessels
as a diagnostic method for other pathological processes. Retinal vessel measurement can
be useful for diagnosing pathologies related to cardiovascular risk [26,34,41] and hyper-
tension [26,33,34,36], dementia and stroke [35], glaucoma [37], chronic kidney disease [11],
glycemic control in children [40], myopia [39], and severity of diabetic macular edema [45].
The second category comprises articles aimed at developing automated retinal vessel
measurement systems. These articles cover several levels of development: those that use
systems limited to vessel segmentation [46,49,51]; those that include vessel labeling and
creation of the vascular tree [31,42,45,47,52]; and those that calculate AVR in order to grade
hypertensive retinopathy [43,44,49,53].

4. Discussion
This scoping review aimed to summarize the research available on automated retinal
vessel analysis systems in order to determine where automated AVR calculation systems
are currently at in terms of implementation. The results indicate that interest in developing
technology that facilitates the analysis of the retinal microvascular network has increased
over the past eight years. Publications from 2014 and earlier refer to experiments to test
the algorithms developed. As of 2015, the software developed from these algorithms has
been introduced into clinical practice, demonstrating advantages in real-life scenarios, even
though it is not yet widely nor systematically employed. The results of this review confirm
that automated AVR calculation systems have not just been introduced as a diagnostic tool
for retinal vascular disorders in the field of ophthalmology, but they have been extensively
applied in other medical specialties as an accessible and efficient diagnostic tool for other
pathologies. Numerous findings indicate that retinal vascular caliber is associated with var-
ious systemic diseases, such as hypertension, obesity, diabetes, chronic kidney disease, and
stroke. Moreover, since AVR is associated with the development of cardiovascular disease,
examining it in this way offers a non-invasive view into the systemic microvasculature.
Hypertensive retinopathy is an indicator of damage to other target organs. However,
it is difficult for ophthalmologists to study hypertensive retinopathy in the early stages.
Therefore, further research should be conducted on computer-assisted diagnoses that
use AVR calculation to automatically detect hypertensive retinopathy and grade it in its
early stages [54].
The automation of processes is a prerequisite to improving the affordability, efficiency,
and accessibility of these procedures [55] and reducing the high subjectivity of manually
assessing AVR [56]. Deep learning methods arise to compute AVR. Convolutional Neural
Networks (CNN, Atlanta, GA, USA) obtain a good approximation of AVR value by applying
a sequence of spatial filters, subsampling, and non-linear operations.
The clinical applications of artificial intelligence in automated AVR reading could
cover a wide range of tasks, including automating hypertensive retinopathy screening,
supporting treatment decision-making, assessing systemic vascular status and cardiovascu-
lar mortality [57], prescribing medications and diagnostic tests, and creating prognostic
models of different diseases [58] to provide more efficient, precise, and sensitive methods
in the interpretation of clinical data.
Nonetheless, using artificial intelligence to analyze retinal microvasculature does
present some limitations. Firstly, the images used to validate and train the AI may not have
Diagnostics 2022, 12, 2865 11 of 14

enough ethnic variability to provide high external validity because there must be enough,
but not too many, images for the processes to be efficient. Secondly, the data should
be restricted to those criteria of greatest prognostic relevance, maintaining maximum
diagnostic accuracy and minimum algorithm complexity. Consequently, if these processes
were automated, they could be implemented in primary care for use by trained health
professionals and in rural settings, thus facilitating the classification of cardiovascular risk
and reducing the need to refer cases for evaluation by an ophthalmologist. Overall, this
would result in the optimization of available health resources.

5. Conclusions
In recent years, there has been increased interest in developing technology that facili-
tates the analysis of the retinal microvascular network. Software has been developed and is
being introduced into clinical practice not just as a diagnostic tool in the field of ophthal-
mology, but also in other medical specialties, because there is an established association
between various diseases and retinal vessel alterations.
If automated processes for retinal vessel measurement were implemented in primary
care for use by trained health professionals, fewer cases would need evaluation by an
ophthalmologist, thus optimizing the available health resources.
Moreover, such processes improve the reliability of vasculature measurements, which,
in turn, leads to better classification of hypertensive retinopathy by eliminating observer
subjectivity and taking cardiovascular risk into account. Also, the more reliable the mea-
surements, the better the early diagnosis of other pathologies, such as dementia and stroke.
Further research on the evaluation and implementation of these technologies is needed to
recommend their use.

Author Contributions: Conceptualization, P.T.-M. and V.M.L.-L.; methodology, R.G.-S.; formal

analysis, R.G.-S.; A.H.; E.I.G.; and V.M.L.-L.; investigation, D.V.L.; M.T.A.; R.F.; P.M.-A.; I.B.; and
J.U.A.; writing—original draft preparation, R.G.-S. and V.M.L.-L.; writing—review and editing, R.G.-S.
and A.H.; supervision, P.T.-M.; project administration, R.G.-S. All authors have read and agreed to
the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Cheung, C.Y.; Ikram, M.K.; Sabanayagam, C.; Wong, T.Y. Retinal microvasculature as a model to study the manifestations of
hypertension. Hypertension 2012, 60, 1094–1103. [CrossRef] [PubMed]
2. Screening Programmes by Geography—Retina International’s Diabetic Eye Disease Toolkit. Available online: http://ded.retinaint.
org/screening-innovation-and-clinical-trials/screening-programs-by-geography/ (accessed on 19 May 2021).
3. Nørgaard, M.F.; Grauslund, J. Automated screening for diabetic retinopathy—A systematic review. Ophthalmic. Res. 2018,
60, 9–17. [CrossRef]
4. Nielsen, K.B.; Lautrup, M.L.; Andersen, J.K.H.; Savarimuthu, T.R.; Grauslund, J. Deep Learning—Based Algorithms in Screening
of Diabetic Retinopathy: A Systematic Review of Diagnostic Performance. Ophthalmol. Retin. 2019, 3, 294–304. [CrossRef]
5. Islam, M.M.; Yang, H.C.; Poly, T.N.; Jian, W.S.; Li, Y.C. Deep learning algorithms for detection of diabetic retinopathy in retinal
fundus photographs: A systematic review and meta-analysis. Comput. Methods Programs Biomed. 2020, 191, 105320. [CrossRef]
[PubMed]
6. Rani, A.; Mittal, D. Measurement of Arterio-Venous Ratio for Detection of Hypertensive Retinopathy through Digital Color
Fundus Images. J. Biomed. Eng. Med. Imaging 2015, 2, 35. [CrossRef]
7. Cheung, C.Y.; Tay, W.T.; Mitchell, P.; Wang, J.J.; Hsu, W.; Lee, M.L.; Lau, Q.P.; Zhu, A.L.; Klein, R.; Saw, S.M.; et al. Quantitative
and qualitative retinal microvascular characteristics and blood pressure. J. Hypertens. 2011, 29, 1380–1391. [CrossRef] [PubMed]
Diagnostics 2022, 12, 2865 12 of 14

8. Seidelmann, S.B.; Claggett, B.; Bravo, P.E.; Gupta, A.; Farhad, H.; Klein, B.E.; Klein, R.; Di Carli, M.; Solomon, S.D. Retinal Vessel
Calibers in Predicting Long-Term Cardiovascular Outcomes: The Atherosclerosis Risk in Communities Study. Circulation 2016,
134, 1328–1338. [CrossRef]
9. Poplin, R.; Varadarajan, A.V.; Blumer, K.; Liu, Y.; McConnell, M.V.; Corrado, G.S.; Peng, L.; Webster, D.R. Prediction of
cardiovascular risk factors from retinal fundus photographs via deep learning. Nat. Biomed. Eng. 2018, 2, 158–164. [CrossRef]
10. Ong, Y.T.; Hilal, S.; Cheung, C.Y.; Xu, X.; Chen, C.; Venketasubramanian, N.; Wong, T.Y.; Ikram, M.K. Retinal Vascular Fractals
and Cognitive Impairment. Dement. Geriatr. Cogn. Dis. Extra 2014, 4, 305–313. [CrossRef]
11. Yip, W.; Ong, P.G.; Teo, B.W.; Cheung, C.Y.-L.; Tai, E.S.; Cheng, C.-Y.; Lamoureux, E.; Wong, T.Y.; Sabanayagam, C. Retinal
vascular imaging markers and incident chronic kidney disease: A prospective cohort study. Sci. Rep. 2017, 7, 9374. [CrossRef]
12. Taylor, A.M.; MacGillivray, T.J.; Henderson, R.D.; Ilzina, L.; Dhillon, B.; Starr, J.M.; Deary, I.J. Retinal vascular fractal dimension,
childhood IQ, and cognitive ability in old age: The lothian birth cohort study 1936. PLoS ONE 2015, 10, e0121119. [CrossRef]
[PubMed]
13. Cheung, C.; Ikram, M.K.; Chen, C.; Wong, T.Y. Imaging retina to study dementia and stroke. Prog. Retin. Eye Res. 2017, 57, 89–107.
[CrossRef] [PubMed]
14. McGeechan, K.; Liew, G.; MacAskill, P.; Irwig, L.; Klein, R.; Klein, B.E.; Wang, J.J.; Mitchell, P.; Vingerling, J.R.; de Jong, P.T.; et al.
Prediction of incident stroke events based on retinal vessel caliber: A systematic review and individual-participant meta-analysis.
Am. J. Epidemiol. 2009, 170, 1323–1332. [CrossRef]
15. Forés, R.; Manresa, J.M.; López-Lifante, V.M.; Heras, A.; Delgado, P.; Vázquez, X.; Ruiz, S.; Alzamora, M.T. Relationship between
retinal microvasculature, cardiovascular risk and silent brain infarction in hypertensive patients. Diagnostics 2021, 11, 937.
[CrossRef] [PubMed]
16. Thom, S.; Stettler, C.; Stanton, A.; Witt, N.; Tapp, R.; Chaturvedi, N.; Allemann, S.; Mayet, J.; Sever, P.; Poulter, N.; et al. Differential
effects of antihypertensive treatment on the retinal microcirculation: An anglo-scandinavian cardiac outcomes trial substudy.
Hypertension 2009, 54, 405–408. [CrossRef] [PubMed]
17. Reid, C.M.; Storey, E.; Wong, T.Y.; Woods, R.; Tonkin, A.; Wang, J.J.; Kam, A.; Janke, A.; Essex, R.; Abhayaratna, W.; et al. Aspirin
for the prevention of cognitive decline in the elderly: Rationale and design of a neuro-vascular imaging study (ENVIS-ion). BMC
Neurol. 2012, 12, 3. [CrossRef]
18. Bhaduri, B.; Nolan, R.M.; Shelton, R.L.; Pilutti, L.A.; Motl, R.W.; Moss, H.E.; Pula, J.H.; Boppart, S.A. Detection of retinal blood
vessel changes in multiple sclerosis with optical coherence tomography. Biomed. Opt. Express 2016, 7, 2321. [CrossRef]
19. Petzold, A.; de Boer, J.F.; Schippling, S.; Vermersch, P.; Kardon, R.; Green, A.; Calabresi, P.A.; Polman, C. Optical coherence
tomography in multiple sclerosis: A systematic review and meta-analysis. Lancet Neurol. 2010, 9, 921–932. [CrossRef]
20. Saidha, S.; Sotirchos, E.S.; Ibrahim, M.A.; Crainiceanu, C.M.; Gelfand, J.M.; Sepah, Y.J.; Ratchford, J.N.; Oh, J.; Seigo, M.A.;
Newsome, S.D.; et al. Microcystic macular oedema, Thickness of the inner nuclear layer of the retina, and disease characteristics
in multiple sclerosis: A retrospective study. Lancet Neurol. 2012, 11, 963–972. [CrossRef]
21. Meier, M.H.; Gillespie, N.A.; Hansell, N.K.; Hewitt, A.W.; Hickie, I.B.; Lu, Y.; MacGregor, S.; Medland, S.E.; Sun, C.; Wong,
T.Y.; et al. Associations between depression and anxiety symptoms and retinal vessel caliber in adolescents and young adults.
Psychosom. Med. 2014, 76, 732–738. [CrossRef]
22. Yildiz, M.; Alim, S.; Batmaz, S.; Demir, S.; Songur, E.; Ortak, H.; Demirci, K. Duration of the depressive episode is correlated with
ganglion cell inner plexifrom layer and nasal retinal fiber layer thicknesses: Optical coherence tomography findings in major
depression. Psychiatry Res.-Neuroimaging 2016, 251, 60–66. [CrossRef] [PubMed]
23. Celik, M.; Kalenderoglu, A.; Sevgi Karadag, A.; Bekir Egilmez, O.; Han-Almis, B.; Şimşek, A. Decreases in ganglion cell layer
and inner plexiform layer volumes correlate better with disease severity in schizophrenia patients than retinal nerve fiber layer
thickness: Findings from spectral optic coherence tomography. Eur. Psychiatry 2016, 32, 9–15. [CrossRef] [PubMed]
24. Meier, M.H.; Shalev, I.; Moffitt, T.E.; Kapur, S.; Keefe, R.S.; Wong, T.Y.; Belsky, D.W.; Harrington, H.; Hogan, S.; Houts, R.; et al.
Microvascular abnormality in schizophrenia as shown by retinal imaging. Am. J. Psychiatry 2013, 170, 1451–1459. [CrossRef]
[PubMed]
25. Wainwright, A.; Liew, G.; Burlutsky, G.; Rochtchina, E.; Zhang, Y.P.; Hsu, W.; Lee, J.M.; Wong, T.Y.; Mitchell, P.; Wang, J.J. Effect of
image quality, color, and format on the measurement of retinal vascular fractal dimension. Investig. Ophthalmol. Vis. Sci. 2010,
51, 5525–5529. [CrossRef] [PubMed]
26. Maderuelo-Fernandez, J.A.; Garcia-Garcia, A.; Chamoso, P.; Recio-Rodríguez, J.I.; Rodríguez-González, S.; Patino-Alonso, M.C.;
Rodriguez-Sanchez, E.; Corchado-Rodríguez, J.M.; Gómez-Marcos, M.A.; Garcia-Ortiz, L. Automatic image analyser to assess
retinal vessel calibre (ALTAIR). A new tool to evaluate the thickness, area and length of the vessels of the retina. Int. J. Med.
Inform. 2020, 136, 104090. [CrossRef]
27. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.J.; Horsley, T.; Weeks, L.; et al.
PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann. Intern. Med. 2018, 169, 467–473.
[CrossRef]
28. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.;
Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, 89.
[CrossRef]
Diagnostics 2022, 12, 2865 13 of 14

29. Badawi, S.A.; Fraz, M.M.; Shehzad, M.; Mahmood, I.; Javed, S.; Mosalam, E.; Nileshwar, A.K. Detection and Grading of
Hypertensive Retinopathy Using Vessels Tortuosity and Arteriovenous Ratio. J. Digit. Imaging 2022, 35, 281–301. [CrossRef]
30. Huang, Y.; Zhou, H.; Zhang, S.; Zhong, X.; Lin, Y.; Xiong, Z.; Liu, M.; Yimamu, A.; Christopher, O.; Zhou, Z.; et al. Mid- to
Late-Life Time-Averaged Cumulative Blood Pressure and Late-Life Retinal Microvasculature: The ARIC Study. J. Am. Heart Assoc.
2022, 11, e25226. [CrossRef]
31. Irshad, S.; Yin, X.; Zhang, Y. A new approach for retinal vessel differentiation using binary particle swarm optimization. Comput.
Methods Biomech. Biomed. Eng. Imaging Vis. 2021, 9, 510–522. [CrossRef]
32. Dai, G.; He, W.; Xu, L.; Pazo, E.E.; Lin, T.; Liu, S.; Zhang, C. Exploring the effect of hypertension on retinal microvasculature using
deep learning on East Asian population. PLoS ONE 2020, 15, e0230111. [CrossRef] [PubMed]
33. Robertson, G.; Fleming, A.; Williams, M.C.; Trucco, E.; Quinn, N.; Hogg, R.; McKay, G.J.; Kee, F.; Young, I.; Pellegrini, E.; et al.
Association between hypertension and retinal vascular features in ultra-widefield fundus imaging. Open Hear. 2020, 7, e001124.
[CrossRef] [PubMed]
34. Tapp, R.J.; Owen, C.G.; Barman, S.A.; Welikala, R.A.; Foster, P.J.; Whincup, P.H.; Strachan, D.P.; Rudnicka, A.R.; UK Biobank Eye
and Vision Consortium. Associations of retinal microvascular diameters and tortuosity with blood pressure and arterial stiffness
United Kingdom biobank. Hypertension 2019, 74, 1383–1390. [CrossRef]
35. Lau, A.Y.; Mok, V.; Lee, J.; Fan, Y.; Zeng, J.; Lam, B.; Wong, A.; Kwok, C.; Lai, M.; Zee, B. Retinal image analytics detects white
matter hyperintensities in healthy adults. Ann. Clin. Transl. Neurol. 2019, 6, 98–105. [CrossRef] [PubMed]
36. He, Y.; Li, S.M.; Kang, M.T.; Liu, L.R.; Li, H.; Wei, S.F.; Ran, A.R.; Wang, N. Anyang Childhood Eye Study Group. Association
between blood pressure and retinal arteriolar and venular diameters in Chinese early adolescent children, and whether the
association has gender difference: A cross-sectional study. BMC Ophthalmol. 2018, 18, 133. [CrossRef]
37. Adiarti, R.; Ekantini, R.; Agni, A.N.; Wong, T.Y.; Sasongko, M.B. Retinal Arteriolar Narrowing in Young Adults with Glaucomatous
Optic Disc. J. Glaucoma 2018, 27, 699–702. [CrossRef]
38. Akbar, S.; Akram, M.U.; Sharif, M.; Tariq, A.; Yasin, U. Arteriovenous ratio and papilledema based hybrid decision support
system for detection and grading of hypertensive retinopathy. Comput. Methods Programs Biomed. 2018, 154, 123–141. [CrossRef]
39. Iwase, A.; Sekine, A.; Suehiro, J.; Tanaka, K.; Kawasaki, Y.; Kawasaki, R.; Sinai, M.J.; Araie, M. A new method of magnification
correction for accurately measuring retinal vessel calibers from fundus photographs. Investig. Ophthalmol. Vis. Sci. 2017,
58, 1858–1864. [CrossRef]
40. Li, L.J.; Lamoureux, E.; Wong, T.Y.; Lek, N. Short-term poor glycemic control and retinal microvascular changes in pediatric Type
1 Diabetes patients in Singapore: A pilot study. BMC Ophthalmol. 2017, 17, 60. [CrossRef]
41. Vázquez Dorrego, X.M.; Manresa Domínguez, J.M.; Heras Tebar, A.; Forés, R.; Girona Marcé, A.; Alzamora Sas, M.T.; Delgado
Martínez, P.; Riba-Llena, I.; Ugarte Anduaga, J.; Beristain Iraolai, A.; et al. Semi-automatic measuring of arteriovenous relation as
a possible silent brain infarction risk index in hypertensive patients. Arch. Soc. Española Oftalmol. 2016, 91, 513–519. [CrossRef]
42. Cavallari, M.; Stamil, C.; Umeton, R.; Calimeri, F.; Orzi, F. Novel Method for Automated Analysis of Retinal Images: Results in
Subjects with Hypertensive Retinopathy and CADASIL. BioMed Res. Int. 2015, 2015, 752957. [CrossRef] [PubMed]
43. Fraz, M.M.; Welikala, R.A.; Rudnicka, A.R.; Owen, C.G.; Strachan, D.P.; Barman, S.A. QUARTZ: Quantitative analysis of retinal
vessel topology and size - An automated system for quantification of retinal vessels morphology. Expert Syst. Appl. 2015,
42, 7221–7234. [CrossRef]
44. Estrada, R.; Allingham, M.J.; Mettu, P.S.; Cousins, S.W.; Tomasi, C.; Farsiu, S. Retinal Artery-Vein Classification via Topology
Estimation. IEEE Trans. Med. Imaging 2015, 34, 2518–2534. [CrossRef] [PubMed]
45. Moradi, A.; Sepah, Y.J.; Ibrahim, M.A.; Sophie, R.; Moazez, C.; Bittencourt, M.G.; Annam, R.E.; Hanout, M.; Liu, H.; Ferraz,
D.; et al. Association of retinal vessel calibre and visual outcome in eyes with diabetic macular oedema treated with ranibizumab.
Eye 2014, 28, 1315–1320. [CrossRef] [PubMed]
46. Franklin, S.W.; Rajan, S.E. Retinal vessel segmentation employing ANN technique by Gabor and moment invariants-based
features. Appl. Soft Comput. J. 2014, 22, 94–100. [CrossRef]
47. Dashtbozorg, B.; Mendonca, A.M.; Campilho, A. An automatic graph-based approach for artery/Vein classification in retinal
images. IEEE Trans. Image Process. 2014, 23, 1073–1083. [CrossRef]
48. Vázquez, S.G.; Barreira, N.; Penedo, M.G.; Rodríguez-Blanco, M. Reliable monitoring system for arteriovenous ratio computation.
Comput. Med. Imaging Graph. 2013, 37, 337–345. [CrossRef]
49. Huang, Y.; Zhang, J.; Huang, Y. An automated computational framework for retinal vascular network labeling and branching
order analysis. Microvasc. Res. 2012, 84, 169–177. [CrossRef]
50. Ortega, M.; Barreira, N.; Novo, J.; Penedo, M.G.; Pose-Reino, A.; Gómez-Ulla, F. Sirius: A web-based system for retinal image
analysis. Int. J. Med. Inform. 2010, 79, 722–732. [CrossRef]
51. Villalobos-Castaldi, F.M.; Felipe-Riverón, E.M.; Sánchez-Fernández, L.P. A fast, efficient and automated method to extract vessels
from fundus images. J. Vis. 2010, 13, 263–270. [CrossRef]
52. Vázquez, S.G.; Cancela, B.; Barreira, N.; Penedo, M.G.; Rodríguez-Blanco, M.; Seijo, M.P.; de Tuero, G.C.; Barceló, M.A.; Saez,
M. Improving retinal artery and vein classification by means of a minimal path approach. Mach. Vis. Appl. 2013, 24, 919–930.
[CrossRef]
53. Akbar, S.; Akram, M.U.; Sharif, M.; Tariq, A.; Khan, S.A. Decision support system for detection of hypertensive retinopathy using
arteriovenous ratio. Artif. Intell. Med. 2018, 90, 15–24. [CrossRef] [PubMed]
Diagnostics 2022, 12, 2865 14 of 14

54. Mancia, G.; Fagard, R.; Narkiewicz, K.; Redón, J.; Zanchetti, A.; Böhm, M.; Christiaens, T.; Cifkova, R.; De Backer, G.; Dominiczak,
A.; et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the management of arterial
hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur. Heart J. 2013,
34, 2159–2219. [CrossRef] [PubMed]
55. Abràmoff, M.D.; Lou, Y.; Erginay, A.; Clarida, W.; Amelon, R.; Folk, J.C.; Niemeijer, M. Improved automated detection of diabetic
retinopathy on a publicly available dataset through integration of deep learning. Investig. Ophthalmol. Vis. Sci. 2016, 57, 5200–5206.
[CrossRef]
56. Manresa, J.M.; Forés, R.; Vázquez, X.; Alzamora, M.T.; Heras, A.; Delgado, P.; Torán-Montserrat, P. Reliability of retinography for
the detection of hypertensive retinopathy in Primary Care. Aten. Primaria 2020, 52, 410–417. [CrossRef]
57. Arnould, L.; Binquet, C.; Guenancia, C.; Alassane, S.; Kawasaki, R.; Daien, V.; Tzourio, C.; Kawasaki, Y.; Bourredjem, A.; Bron,
A.; et al. Association between the retinal vascular network with Singapore ‘i’ Vessel Assessment (SIVA) software, cardiovascular
history and risk factors in the elderly: The Montrachet study, population-based study. PLoS ONE 2018, 13, e0194694. [CrossRef]
58. Schmidt-Erfurth, U.; Sadeghipour, A.; Gerendas, B.S.; Waldstein, S.M.; Bogunović, H. Artificial intelligence in retina. Prog. Retin.
Eye Res. 2018, 67, 1–29. [CrossRef]