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Review
Retinal venous occlusion and its association with atherosclerotic vascular disease
Oclusión venosa de retina y su asociación con la enfermedad vascular aterosclerótica
María Larrousse Morellóna,
Corresponding author
mlarrousse.germanstrias@gencat.cat

Corresponding author.
, Yéssica López Loureiroa, Susana Ruiz Bilbaob
a Servicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain
b Servicio de Oftalmología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Retinal venous occlusion &#40;RVO&#41; is the second most prevalent cause of vascular vision loss after diabetic retinopathy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of RVO stands at 0&#46;77&#37; among people aged 30&#8211;89 years&#44; and there are an estimated 28&#46;06 million people with RVO worldwide in 2015&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Retinal vein occlusions are classified according to the anatomical location where the retinal vein occlusion occurs in the retina and are divided into 2 main categories&#58; central retinal vein occlusions &#40;CRVO&#41; and branch retinal vein occlusions &#40;BRVO&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In CRVO&#44; the occlusion is located near the lamina cribrosa next to the optic nerve&#44; with greater visual impairment due to greater alteration of the retinal vascular territory&#44; and less likelihood of spontaneous resolution&#46; In BRVO it occurs in one of the branches and is divided into quadrants&#46; The most common location of BRVO is the superior temporal region as this is where the arteriovenous crossings are most numerous&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The prevalence of the 2 main groups of RVO is different&#44; with 0&#46;13&#37; in CRVO and 0&#46;64&#37; in RVO&#46; The cumulative incidence of RVO at 5 years is 0&#46;86&#37; and at 10 years is 1&#46;63&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It appears that the Asian population is more likely to be predisposed to developing RVO&#44; although the distribution is not clear as not all races are represented in epidemiological studies&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The prevalence of RVO does not vary with gender but is clearly related to age&#46; The probability of having a RVO increases by 60&#37; for each decade of life&#44; i&#46;e&#46; the prevalence among 30&#8211;39-year-olds is 0&#46;26&#37;&#44; progressively increasing to 3&#46;39&#37; among 80&#8211;89-year-olds&#46; The age range with the highest number of cases is 60&#8211;69 years for all types of RVO&#44; and 70&#8211;79 years for CRVO&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although information on recurrence in the same eye is limited&#44; it is estimated that contralateral involvement is 10&#37; over time&#44; although in the first year it may be 5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Signs and symptoms</span><p id="par0035" class="elsevierStylePara elsevierViewall">The main clinical manifestation of RVO is an acute&#44; painless&#44; monocular decrease in visual acuity &#40;VA&#41;&#46; The symptoms of RVO can be mild&#44; and in a small number of cases the process resolves spontaneously&#46; However&#44; the decrease in VA can be severe&#44; especially if the affected territory includes the macula&#46; Visual loss may not be detected for several days or weeks&#44; especially in patients without foveal involvement&#46; In most cases&#44; RVO involvement is unilateral&#44; but may be bilateral in 5&#8211;6&#37; of RVOs and 10&#37; of CRVOs&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Therefore&#44; clinical manifestations and severity of reduced VA depend on RVO location&#44; extent and macular involvement&#46; In the absence of macular involvement&#44; the patient may only have a perimetric defect that is inversely related to the location of the affected retina&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Ophthalmoscopic findings are the basis for diagnosis&#46; The acute phase of CRVO is characterised by tortuosity and venous dilatation&#44; superficial flame-shaped haemorrhages in the venous tract in the 4 quadrants of the retina&#44; macular oedema&#44; cotton-wool exudates in the nerve fibre layer and&#44; occasionally&#44; papilledema&#46; There may be an afferent pupillary defect&#44; which is associated with ischaemic forms&#44; whereas in BRVO the same findings are localised in the affected branch&#44; a sector well delimited by the drainage area of the vein&#46; It is usually associated with macular oedema&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Dilatation and venous tortuosity with the formation of intraretinal vascular shunts or optic nerve head &#40;&#8220;optociliary&#8221;&#41; in non-ischaemic retinas are observed in the chronic phase of CRVO&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The most common complication of RVO is macular oedema&#44; and it is the most common cause of acute or chronic visual loss in any form of RVO&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Retinal ischaemia is the worst ocular complication because it lacks effective treatment and can trigger neovascularisation in half of the patients&#46; This process is an abnormal compensatory mechanism based on the release of vascular endothelial growth factors that will lead to further ocular complications such as retinal&#44; papillary and iridial neovascularisation&#46; A serious complication of neovascularisation is neovascular glaucoma and vitreous haemorrhage&#46; Irreversible central visual loss due to macular ischaemia may also occur&#46; The process of conversion from a RVO to an ischaemic form is very rapid and often occurs in the first trimester&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In addition to fundus examination&#44; macular optical coherence tomography &#40;OCT&#41; is the reference technique to assess the presence and progress of macular oedema&#44; as well as to quantify the thickness of macular oedema and the thickness of the ganglion cells&#46; OCT-angiography assesses the existence of macular ischaemia or non-perfusion&#46; On the other hand&#44; OCT can distinguish signs that will serve as markers of retinal inflammation and also provide additional information such as the presence of vitreoretinal interface abnormalities and&#47;or loss of outer retinal integrity that can further limit vision and guide treatment&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Fluorescein angiography can assess for retinal ischaemia and should not be performed in the acute phase of RVO because of interference with retinal haemorrhages&#59; it can also detect neovascularisation that may not be clinically apparent&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The assessment of VA is usually performed with optical correction measured by <span class="elsevierStyleItalic">Early Treatment Diabetic Retinopathy Retinopathy Study</span> &#40;ETDRS&#41; optotypes&#44; a scale that allows the measurement of VA in cases of low vision in a standardised and reproducible way&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathophysiology</span><p id="par0075" class="elsevierStylePara elsevierViewall">Different pathological mechanisms have been proposed for RVO&#44; making its pathophysiology controversial and possibly a heterogeneous and multifactorial process&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Classically&#44; it has been proposed that RVO is caused by haemodynamic changes secondary to Virchow&#39;s classic triad&#58; endothelial injury to the vein creates a state of hypercoagulability and turbulent or abnormal blood flow&#46; Increased hypercoagulability is generated by various stimuli&#44; such as infection&#44; cancer&#44; mechanical compression or thrombophilia associated with certain diseases&#46; <span class="elsevierStyleItalic">Venous stasis</span> activates coagulation factors&#44; creating a prothrombotic milieu&#44; increased viscosity and endothelial damage leading to venous occlusion&#46; Thrombus production generates a vicious feedback loop&#44; with increased activation of procoagulant mediators&#44; platelet activation and increased inflammatory cytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies in the last decade have suggested that changes in the retinal artery may result in compression of the retinal vein&#46; In CRVO&#44; the central retinal vein and central retinal artery share the adventitia and circulate alongside the optic nerve in a small anatomical space<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Therefore&#44; several studies suggest that increased pressure in the central retinal artery could lead to mechanical occlusion of the central retinal vein&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In the case of BRVO&#44; venous occlusion occurs almost invariably at arteriovenous crossings&#44; where the artery and vein also share the tunica adventitia&#46; For this reason&#44; any arterial condition involving an increase in size or stiffness will involve mechanical narrowing of the vein lumen leading to slowing of blood flow and loss of laminar conduction&#44; resulting in a prothrombotic milieu&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Once a venous occlusion has occurred&#44; this effect is translated into an increase in vascular pressure behind the occlusion&#44; causing fluid to leak through the vessel wall into the adjacent retinal tissue&#46; The affected endothelium initiates chronic low-grade inflammation in the retinal microvasculature and activation of inflammatory mediators&#44; increasing the permeability of the blood-retinal barrier and perpetuating oedema&#46; Increased membrane permeability is also mediated by vascular endothelial growth factor &#40;VEGF&#41;&#44; increasing vessel permeability and generating more oedema &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Another hypothesis is that atherosclerosis leads to arterial insufficiency&#44; which in turn leads to retinal hypoperfusion with production of hypoxia-inducible factor and VEGF&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Another mechanism that would at least partially explain the pathophysiology of CRVO is the increased stiffness of the lamina cribrosa&#44; which becomes stiffer and thicker&#44; a phenomenon associated with ageing&#46; In contrast&#44; in young patients with RVO&#44; without other associated factors&#44; it has been proposed that dehydration due to intense physical exercise could lead to increased viscosity&#44; vascular inflammation and a plausible mechanism for RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Possible associated ophthalmological congenital anomalies or compressive anatomical factors&#44; which are uncommon in these patients&#44; are also considered&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Another pathophysiological mechanism is the increase in intraocular pressure&#44; which causes changes in the retinal vessels by displacing the lamina cribrosa&#44; resulting in turbulent venous flow and endothelial changes&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Aetiology</span><p id="par0105" class="elsevierStylePara elsevierViewall">The aetiology of RVO is diverse&#46; Current evidence suggests that its most common aetiology is related to the atherosclerotic process&#44; although it has also been associated with thrombophilia&#44; autoinflammatory diseases&#44; haematological diseases&#44; infections&#44; drugs and certain ophthalmological conditions&#46; Several authors consider that young patients without associated cardiovascular risk factors &#40;CVRFs&#41; who have RVO should have a different diagnostic approach&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the main diseases associated with RVO&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Atherosclerotic disease</span><p id="par0110" class="elsevierStylePara elsevierViewall">Patients with RVO have more CVRFs&#44; more subclinical atherosclerotic disease and an increased prevalence of cardiovascular disease compared to the general population&#46; On the other hand&#44; from a pathophysiological point of view&#44; it has been shown that RVO is associated with increased endothelial dysfunction independently of classical CVRFs&#46; This is important as it indicates that these patients with RVO have a higher severity of atherosclerotic disease&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Cardiovascular risk factors</span><p id="par0115" class="elsevierStylePara elsevierViewall">The factors found to be associated with RVO according to the Song et al&#46; study are summarised in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">The Gutenberg Healthy Study showed that 91&#46;5&#37; of patients with RVO had one or more CVRFs while this percentage was 75&#46;9&#37; in age- and sex-matched controls without RVO&#46; This study also showed that age&#44; history of hypertension &#40;HT&#41;&#44; family history of stroke and atrial fibrillation were associated with RVO in general or with one of its subgroups&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> On the other hand&#44; patients with RVO have an elevated risk of cardiovascular events according to the Framingham scale&#46; This effect is more significant in patients who smoke and is clearly higher than in controls without RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">HT is the most important risk factor for RVO&#44; with a prevalence ranging from 62&#8211;70&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> The diagnosis of unknown HT at the onset of RVO is not uncommon&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a> In addition&#44; hypertensive patients with RVO are more likely to have a non-dipper HT profile&#44; characterised by a lack of physiological blood pressure reduction during sleep&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Uncontrolled HT is associated with greater deterioration of VA produced by RVO and is also associated with greater severity of macular oedema following RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Even patients with mild HT are at higher risk of developing RVO than normotensive patients&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The combination of hypertension and dyslipidaemia&#44; as well as metabolic syndrome&#44; is common in RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Dyslipidaemia may be found as the only CVRF&#44; especially in young patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;11</span></a> On the other hand&#44; statin treatment seems to decrease the risk of developing RVO&#44; but it is not known whether its protective effect could be related to improved metabolic control or could be explained by other factors&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Statin treatment has also been shown to decrease the risk of a cardiovascular event in patients with RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> However&#44; statin therapy does not improve the prognosis of macular oedema&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Elevated lipoprotein&#40;a&#41; levels are an independent risk factor for atherosclerosis and venous thrombosis&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and its elevation is associated with an increased risk of developing RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The association between RVO and the presence of diabetes mellitus &#40;DM&#41; is controversial&#46; While the meta-analysis by Song et al&#46; does not describe DM as a risk factor for developing RVO &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; the meta-analysis by Wang et al&#46; concludes that patients with DM have a 68&#37; increased risk of developing RVO compared to patients without DM&#59; but this association would be exclusively related to CRVO&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Smoking is common among patients with RVO&#44;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;15</span></a> and may be related to worse VA outcome at the end of treatment&#44; in particular in patients with CRVO&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> It has been postulated that smoking reduces retinal blood flow and impairs the ability of retinal vessels to self-regulate in response to ischaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Overweight and obesity are associated with RVO&#46; One study shows that patients with a higher body mass index&#44; even if they are not diabetic&#44; have a higher risk of RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Another study shows that obesity is the second most prevalent CVRF after hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Other factors</span><p id="par0155" class="elsevierStylePara elsevierViewall">Patients with obstructive sleep apnoea are three times more likely to develop RVO than the general population&#44; especially if they have hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Subclinical vascular disease</span><p id="par0160" class="elsevierStylePara elsevierViewall">Patients with RVO have greater target organ involvement&#44; with increased presence of atheromatous plaques in the carotid bifurcation&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Microalbuminuria&#44; even in the early stages&#44; has also been found to be a risk factor for developing RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Furthermore&#44; a higher prevalence of left ventricular hypertrophy has been reported in patients with RVO and hypertension&#44; mainly in those with CRVO&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Cardiovascular disease</span><p id="par0165" class="elsevierStylePara elsevierViewall">The higher prevalence of cardiovascular disease has been observed in large meta-analyses of patients with RVO&#46; The meta-analysis by Wu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> included 15 prospective case-control cohort studies evaluating more than 60&#44;000 patients with RVO and 400&#44;000 controls adjusted for risk factors&#44; age and sex&#46; RVO was associated with a 45&#37; increased risk of stroke&#44; 26&#37; increased risk of myocardial infarction&#44; 53&#37; increased risk of heart failure&#44; 26&#37; increased risk of obliterative vascular disease and 36&#37; increased overall mortality but was not associated with an increased risk of cardiovascular mortality&#46; Similar results have been found by another meta-analysis&#44; but without detecting an increase in overall mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Results from the Danish cohort<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> confirm the increased risk of cardiovascular events and describe a 12&#37; increase in all-cause mortality&#44; but only in the subgroup of patients with CRVO&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> describes the main cohort studies of patients with RVO and their association with mortality&#44; ischaemic heart disease and cerebral vascular disease&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">Chronic kidney disease &#40;CKD&#41; is closely related to RVO&#46; CKD has been shown to triple the risk of developing RVO and its prevalence in patients with RVO is 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> In a study of CKD patients on haemodialysis&#44; the authors show that the risk of RVO is halved after kidney transplantation&#44; which may be related more to the improvement in renal function than to the control of classic CVRFs&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The prevalence of obliterative vascular disease&#44; non-valvular atrial fibrillation and heart failure is higher in patients with RVO than in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;33&#8211;35</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">It has been reported that patients who have had an RVO have an increased risk of developing any type of dementia&#44; especially vascular dementia&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Genetic and acquired thrombophilia</span><p id="par0185" class="elsevierStylePara elsevierViewall">Until a decade ago&#44; RVO was considered to be an atypical site of venous thromboembolic disease associated with inherited or acquired thrombophilia&#46; Only 3&#37; of patients are described as having venous thromboembolic disease &#40;VTE&#41; prior to the diagnosis of RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Numerous studies link an increased risk of RVO to thrombophilia&#44; however&#44; this hypothesis is based on small&#44; selected&#44; retrospective cohorts&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">In relation to thrombophilia&#44; hyperhomocysteinemia and antiphospholipid syndrome deserve special attention because of their association with RVO in meta-analyses&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> however&#44; this increased risk is not subsequently confirmed in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Elevated homocysteine levels may be due to a genetic alteration&#44; but levels can also be increased by various dietary or systemic alterations&#44; leading to atheromatosis and VTE&#46; In addition&#44; elevated homocysteine levels are common in acute RVO&#44; whether or not associated with folic acid deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Antiphospholipid syndrome is characterised by arterial&#44; venous and microvascular thrombosis together with elevated antibodies &#40;lupus anticoagulant&#44; cardiolipin&#44; anti-&#946; 2 glycoprotein I&#41;&#46; Triple positive results for these antibodies are associated with a two-fold increased risk of developing RVO&#46; Patients with RVO may have elevated levels of anti-cardiolipin antibodies&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> but they have not been found to be associated with lupus antibodies&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">No association was found between acquired or genetic thrombophilia and RVO in the largest systematic review of thrombophilia to date&#44; which included 95 cohort studies&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> Even so&#44; the diagnostic study should be conducted depending on the characteristics of the patient&#44; namely&#58; in the young patient without other associated diseases&#44; when there is previous VTE or bilateral ocular involvement&#46; Clinical guidelines already state that it is not necessary to perform a systematic thrombophilia study in all patients with RVO&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Autoinflammatory diseases</span><p id="par0215" class="elsevierStylePara elsevierViewall">Autoinflammatory diseases have been associated with RVO&#44; mainly systemic lupus erythematosus &#40;SLE&#41;&#46; Patients with SLE disease have a threefold increased risk of developing RVO compared to the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> The association of RVO with other vasculitides is also described &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; It is worth noting that patients with psoriasis have a 72&#37; increased risk of developing RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Haematological and neoplastic diseases</span><p id="par0220" class="elsevierStylePara elsevierViewall">Haematological diseases<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> have been associated with RVO by inducing a prothrombotic state &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; On the other hand&#44; the Danish cohort study with a 3-year follow-up concludes that patients with RVO are more likely to be diagnosed with a neoplastic process than the general population&#44; with no differences in the type of neoplasm detected&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Infectious diseases</span><p id="par0225" class="elsevierStylePara elsevierViewall">Cases and case series of patients with acute RVO associated with a diagnosis of COVID-19 have been reported&#46; A Spanish multicentre case cohort reported that these patients with RVO associated with COVID-19 were characterised by being younger than 60 years of age and having a good visual prognosis&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> with no known causal association&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> Patients with RVO following SARS-CoV-2 vaccination have also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Infections with chorioretinitis or retinitis have been rarely described and may also lead to RVO&#46; These infections are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ocular factors</span><p id="par0235" class="elsevierStylePara elsevierViewall">The main ocular cause associated with RVO is advanced open-angle glaucoma&#44; mainly related to CRVO&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> Retrobulbar external compression is another rare cause of RVO &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Related drugs</span><p id="par0240" class="elsevierStylePara elsevierViewall">The relationship between oral contraceptive use and the risk of developing RVO is not well defined in the medical literature&#46; According to clinical guidelines&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a> oral contraceptive treatment should be individualised and discontinuation should be considered in patients who have had RVO&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Diuretics have been associated with the risk of developing RVO&#44; possibly due to volume depletion and&#47;or dehydration induced by these drugs&#44; as have hypotensive drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">A recent observational cohort study shows that sodium-glucose cotransporter 2 &#40;iSGLT2&#41; inhibitors may increase the risk of RVO compared to other hypoglycaemic treatments&#46; However&#44; in this study&#44; patients on iSGLT2 treatment were older and had a higher proportion of patients with CKD than the other group&#46; These two conditions were clearly associated with the risk of having a RVO&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Prognosis</span><p id="par0255" class="elsevierStylePara elsevierViewall">The most important factor determining the prognosis of RVO is the severity of VA impairment at the time of occlusion&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> which is generally related to the initial involvement of the macular retinal layers&#46; Another poor prognostic factor is a delay in diagnosis of more than three months&#44; as this leads to a delay in starting specific treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> Older patients have been reported to have worse VA at the end of treatment compared to younger patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;59</span></a> Men with CRVO have also been reported to have a better outcome than women58 and non-smokers with CRVO have a better visual prognosis at the end of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Treatment</span><p id="par0260" class="elsevierStylePara elsevierViewall">From an ophthalmological point of view&#44; treatment aims to reduce macular oedema and prevent or treat retinal ischaemia leading to neovascularisation&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The mainstay of macular oedema treatment is anti-VEGF agents and delayed-release corticosteroid medication to reduce the inflammatory component&#44; both of which are administered intravitreally&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Laser photocoagulation is performed in cases of retinal ischaemia&#44; and surgery using the posterior vitrectomy technique and intraocular photocoagulation is reserved for cases in which laser therapy is not possible due to vitreous haemorrhage that does not allow retinal visualisation or for cases of recurrent macular oedema with a vitreoretinal traction component&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Systemic treatment of RVO has been the subject of a large number of studies with very different results and methodologies&#46; Neither antiplatelet&#44; anticoagulant nor fibrinolytic treatments have been shown to be effective in preventing and&#47;or altering the natural history of RVO&#44; nor in preventing recurrence&#44; nor in improving VA during follow-up&#59; moreover&#44; they may increase intraocular haemorrhagic events&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> These findings are in contrast to the results of a meta-analysis based on heterogeneous retrospective studies and three small clinical trials&#44; which suggested that low-molecular-weight heparin may reduce recurrence in these patients&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> although this therapy is not recommended in current clinical guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">There is no evidence in the scientific literature as to whether early assessment and pharmacological intervention for all CVRFs in these patients could lead to a better prognosis for VA in patients with RVO&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0285" class="elsevierStylePara elsevierViewall">RVO is the second most common cause of vascular VA loss after diabetic retinopathy&#46; Its early diagnosis and treatment improve visual prognosis&#46; The pathophysiology of RVO is associated with the atherosclerotic process&#46; The patient with RVO has an increased cardiovascular risk due to a higher number of CVRFs and a higher incidence of cardiovascular events&#46; Although RVO has not been associated with increased cardiovascular mortality&#44; some large cohort studies show increased overall mortality associated with CRVO&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#44;36</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Recommendations</span><p id="par0290" class="elsevierStylePara elsevierViewall">A multidisciplinary approach to the disease is a priority in order to improve visual prognosis and reduce cardiovascular events in these patients&#46; At present&#44; there are no specific clinical guidelines recommending more intensive or different treatment of CVRFs in patients with RVO&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Informed consent</span><p id="par0295" class="elsevierStylePara elsevierViewall">No patient data appear in the paper&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0300" class="elsevierStylePara elsevierViewall">The authors declare that they have not received funding for this review&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Retinal venous occlusion &#40;RVO&#41; is the second most frequent cause of decreased visual acuity due to retinal vascular involvement&#44; after diabetic retinopathy&#46; Its etiology is not completely clear&#46; Current scientific evidence suggests that it is related to the atherosclerotic process based on the high number of cardiovascular risk factors and the higher incidence of cardiovascular events in these patients&#46; In fact&#44; RVO has a 45&#37; increased risk of stroke&#44; 26&#37; of acute myocardial infarction and peripheral vascular disease&#44; 53&#37; of heart failure and a 36&#37; increase in overall mortality&#44; compared to the general population adjusted for age&#44; sex and the different cardiovascular risk factors&#46; However&#44; no increase in cardiovascular mortality has been detected&#46; Therefore&#44; a multidisciplinary clinical approach to this entity is essential&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La oclusi&#243;n venosa retiniana &#40;OVR&#41; es la segunda causa m&#225;s frecuente de disminuci&#243;n de la agudeza visual por afectaci&#243;n vascular de la retina&#44; por detr&#225;s de la retinopat&#237;a diab&#233;tica&#46; Su etiolog&#237;a no est&#225; completamente esclarecida&#46; La evidencia cient&#237;fica actual sugiere que estar&#237;a relacionada con el proceso ateroscler&#243;tico en base al elevado n&#250;mero de factores de riesgo cardiovascular y la mayor incidencia de episodios cardiovasculares que tienen estos pacientes&#46; De hecho&#44; la OVR tiene un riesgo aumentado del 45&#37; de presentar un accidente cerebrovascular&#44; un 26&#37; de infarto agudo de miocardio y de arteriopat&#237;a obliterante&#44; un 53&#37; de insuficiencia card&#237;aca y un aumento del 36&#37; de mortalidad global&#44; respecto a la poblaci&#243;n general ajustada por edad&#44; sexo y los diferentes factores de riesgo cardiovascular&#46; Sin embargo&#44; no se ha detectado un aumento de la mortalidad cardiovascular&#46; Por todo ello&#44; es indispensable el abordaje cl&#237;nico multidisciplinar de esta entidad&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ophthalmoscopy of a central retinal vein occlusion &#40;A&#41; with its optical coherence tomography &#40;OCT&#41; and branch retinal vein occlusion &#40;B&#41;&#46; A1&#41; Fundus with central retinal vein occlusion of the right eye&#44; showing haemorrhages in all 4 quadrants&#46; A2&#41; OCT shows macular oedema&#44; with cysts in the inner layers and in the outer plexiform layer&#44; with neurosensory detachment&#44; with disorganization of retinal inner layers &#40;DRIL&#41; and hyperreflective spots &#40;HRS&#41;&#46; B1&#41; Fundus with occlusion of the superior temporal venous branch of the left eye with foveal involvement&#44; with flame-shaped haemorrhages in this territory and also coexistence with macular oedema in OCT &#40;B2&#41;&#44; with thickening of the temporal area of the macula&#44; with intraretinal cysts&#44; DRIL and HRS&#46;</p>"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">SGLT2i&#58; sodium-glucose cotransporter 2 inhibitors&#59; RVO&#58; retinal vein occlusion&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diseases or factors associated with OVR</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Atherosclerotic disease</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Risk factors&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Essential hypertensionDyslipidaemiaDiabetes mellitusTobacco use disorderMetabolic syndromeObesity or overweight&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cardiovascular diseases&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Cerebral vascular accidentIschaemic heart disease or heart failureAtrial fibrillationObliterative arteriopathyVascular dementiaChronic kidney disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Other diseases</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Obstructive sleep apnoea syndrome&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Genetic and acquired thrombophilic diseases</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mutation&#58;</span> Factor V Leiden &#40;rs6025&#41;&#44; Factor II G20210A &#40;rs1799963&#41;&#44; Methylenetetrahydrofolate reductase C677T &#40;rs180113&#41;&#44; PAI-1 4G &#40;rs17998&#41; <span class="elsevierStyleItalic">Deficiency&#58;</span> Antithrombin III&#44; protein C&#44; protein SHyperhomocysteinemiaAntiphospholipid syndrome&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leukaemia&#44; lymphoma&#44; multiple myeloma&#44; Waldenstr&#246;m&#8217;s disease&#44; polycythaemia vera&#44; myeloproliferative diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Autoinflammatory diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systemic lupus erythematosus&#44; Beh&#231;et&#8217;s disease&#44; polyarteritis nodosa&#44; sarcoidosis&#44; Wegener&#8217;s granulomatosis&#44; Goodpasture&#8217;s syndrome&#44; psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Infectious diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Bartonella henselae</span> infection&#44; COVID-19&#44; syphilis&#44; tuberculosis&#44; human immunodeficiency virus type 1&#44; cytomegalovirus&#44; hepatitis C virus&#44; Lyme disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ocular factors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glaucoma&#44; retrobulbar external compression due to neoplasm&#44; inflammatory process or endocrine orbitopathy&#46; Shorter axial length&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pharmacological factors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral contraceptives&#44; diuretics&#44; blood pressure lowering drugs&#44; SGLT2i&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Summary of retinal venous occlusion-related diseases&#46;</p>"
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        "etiqueta" => "Table 2"
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        "fuente" => "Source&#58; Table adapted from the study by Song et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">95&#37; CI&#58; 95&#37; confidence interval&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cardiovascular risk factor or disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Odds ratio</span> &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Advanced age &#40;by more than a decade&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;60 &#40;1&#46;38&#8211;1&#46;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#8239;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;08 &#40;0&#46;76&#8211;1&#46;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;661&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine concentration &#40;by increase of 10&#8239;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;04 &#40;1&#46;02&#8211;1&#46;07&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute myocardial infarction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;23 &#40;1&#46;09&#8211;4&#46;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;028&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total cholesterol &#40;by increase of 1&#8239;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;32 &#40;1&#46;08&#8211;1&#46;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;19 &#40;0&#46;52&#8211;2&#46;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;677&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cerebral vascular accident&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;07 &#40;1&#46;30&#8211;3&#46;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Essential hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;82 &#40;2&#46;12&#8211;3&#46;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#8239;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Risk factors associated with retinal venous occlusion&#46;</p>"
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">AMI&#58; acute myocardial infarction&#59; BRVO&#58; branch retinal vein occlusion&#59; CRVO&#58; central retinal vein occlusion&#59; CVA&#58; cerebrovascular accident&#59; CVD&#58; cardiovascular disease&#59; HR&#58; hazard ratio&#59; IRR&#58; incidence rate ratios&#59; RVO&#58; retinal venous occlusion&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">a&#58; do not report the median age&#46; Some 33&#46;7&#37; were between 60 and 69 years old&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">b&#58; do not report the mean age&#46; 36&#46;8&#37; were between 60 and 69 years old&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">c&#58; do not report the median age&#46; 32&#37; were between 60 and 69 years old&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">d&#58; Age 63&#8211;79&#46;4&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case control &#40;reference&#41; year of publication Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37; CVA patients in each type of RVO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37; AMI patients in each type of RVO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37; Mortality in each type of RVO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shih et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> 2015Taiwan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;10&#44;081 RVO&#59; n&#8239;&#61;&#8239;3&#44;393 CRVO&#59; n&#8239;&#61;&#8239;6&#44;688 BRVO&#59; n&#8239;&#61;&#8239;40&#44;324 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#46;6SD&#8239;&#61;&#8239;4&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;&#8239;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;7&#37; RVO6&#46;4&#37; CRVO6&#46;8&#37; BRVO5&#37; controlsHR&#8239;&#61;&#8239;1&#46;40 &#40;1&#46;29&#8211;1&#46;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;9&#37; RVO4&#37; CRVO3&#46;8&#37; BRVO3&#37; controlsHR&#8239;&#61;&#8239;1&#46;29 &#40;1&#46;15&#8211;1&#46;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;8&#37; RVO34&#46;7&#37; CRVO33&#46;3&#37; BRVO33&#46;4&#37; controlsCardiovascular M&#46; without associationOverall mortality&#58; only associated with CRVO&#44; IRR 1&#46;09 &#40;1&#46;02&#8211;1&#46;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Werther et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> 2011USA&#46; USA&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;4&#44;500 RVO&#59; n&#8239;&#61;&#8239;13&#44;500 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#46;0SD&#8239;&#61;&#8239;13&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RVO&#8239;&#61;&#8239;78 persons &#40;1&#46;16 per 100person&#47;year&#41;&#59; control&#8239;&#61;&#8239;96 &#40;0&#46;52 per 100persons&#47;year&#41;RR&#8239;&#61;&#8239;1&#46;72 &#40;1&#46;27&#8211;2&#46;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3&#37; RVO0&#46;9&#37; controlHR&#8239;&#61;&#8239;1&#46;03 &#40;0&#46;75&#8211;1&#46;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> 2015Korea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;1&#44;031 RVO&#59; n&#8239;&#61;&#8239;5&#44;074 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RVO&#8239;&#61;&#8239;16&#46;8&#37;&#46;Control&#8239;&#61;&#8239;10&#46;7&#37;&#46;HR&#8239;&#61;&#8239;1&#46;48 &#40;1&#46;24-1&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> 2016Korea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;1&#44;677 RVO&#59; n&#8239;&#61;&#8239;8&#44;367 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RVO 7&#46;6&#37;&#59; controls 5&#46;3&#37;&#46;HR&#8239;&#61;&#8239;1&#46;25 &#40;1&#46;02-1&#46;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bertelsen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> 2012Denmark&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;1&#44;168 BRVO&#59; n&#8239;&#61;&#8239;116&#44;800 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#37; BRVO&#59; 6&#37; control&#59;IRR&#8239;&#61;&#8239;1&#46;49 &#40;1&#46;27-1&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7&#37; BRVO&#59; 3&#46;1&#37; controlIRR&#8239;&#61;&#8239;1&#46;24 &#40;0&#46;97-1&#46;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR&#8239;&#61;&#8239;0&#44;94 &#40;0&#44;85-1&#44;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> 2017Taiwan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;37&#44;921 RVO&#59; n&#8239;&#61;&#8239;11&#44;3763 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;4SD&#8239;&#61;&#8239;13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;6&#37; CRVO&#46;3&#46;12&#37; BRVO&#46;2&#46;3&#37; controlHR&#8239;&#61;&#8239;1&#46;12 &#40;1&#46;13-1&#46;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;6&#37; RVO&#59; 13&#46;2&#37; control&#44; HR&#8239;&#61;&#8239;1&#46;3 &#40;0&#46;99&#8211;1&#46;07&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> 2018Taiwan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;22&#44;919 RVO&#59; n&#8239;&#61;&#8239;11&#44;4595 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&#46;8SD&#8239;&#61;&#8239;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;9&#37; RVO&#59; 19&#46;4&#37; controlHR&#8239;&#61;&#8239;1&#46;37 &#40;1&#46;33-1&#46;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No data provided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR&#8239;&#61;&#8239;1&#44;03 &#40;0&#44;99-1&#44;07&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frederiksen el al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> 2023Denmark&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#8239;&#61;&#8239;15&#44;665 RVO&#59; n&#8239;&#61;&#8239;4&#44;179&#44;116 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;8d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischaemic CVD &#40;AMI&#46; ischaemic CVA&#46; obliterative arteriopathy&#41;HR&#8239;&#61;&#8239;1&#46;16 &#40;1&#46;11&#8211;1&#46;21&#41;Non-ischaemic CVD &#40;non-ischaemic CVA&#46; Heart Failure&#46;atrial fibrillation&#46; aortic disease&#41;HR&#8239;&#61;&#8239;1&#46;23 &#40;1&#46;15&#8211;1&#46;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiovascular mortality without associationOverall mortality&#58; only associated with CRVO HR&#8239;&#61;&#8239;1&#46;12 &#40;1&#46;04&#8211;1&#46;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3643982.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Main case-control studies investigating the association between mortality&#44; stroke and acute myocardial infarction in patients with RVO&#46; In order to reduce the length of the table&#44; cohort studies with more than 1&#44;000 patients with RVO were selected&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:60 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global epidemiology of retinal vein occlusion&#58; a systematic review and meta-analysis of prevalence&#44; incidence&#44; and risk factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Song"
                            1 => "Y&#46; Xu"
                            2 => "M&#46; Zha"
                            3 => "Y&#46; Zhang"
                            4 => "I&#46; Rudan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7189/jogh.09.010427"
                      "Revista" => array:3 [
                        "tituloSerie" => "J Glob Health"
                        "fecha" => "2019"
                        "volumen" => "9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "The Royal College of Ophthalmologists"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "titulo" => "Clinical Guidelines&#58; Retinal Vein Occlusion &#40;RVO&#41;"
                        "fecha" => "2022"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;www&#46;rcophth&#46;ac&#46;uk&#47;resources-listing&#47;retinal-vein-occlusion-rvo-guidelines&#47;"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for the management of retinal vein RETINA occlusion by the European Society of Retina Specialists &#40;EURETINA&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "U&#46; Schmidt-Erfurth"
                            1 => "J&#46; Garcia-Arumi"
                            2 => "B&#46;S&#46; Gerendas"
                            3 => "E&#46; Midena"
                            4 => "S&#46; Sivaprasad"
                            5 => "R Tadayoni"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000502041"
                      "Revista" => array:5 [
                        "tituloSerie" => "Ophthalmology"
                        "fecha" => "2019"
                        "volumen" => "242"
                        "paginaInicial" => "123"
                        "paginaFinal" => "162"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sociedad Espa&#241;ola de Retina y V&#237;treo"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Gu&#237;as de Pr&#225;ctica Cl&#237;nica de la SERV"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; G&#243;mez-Ulla"
                            1 => "M&#46;J&#46; Abraldes"
                            2 => "E&#46; Basauri"
                            3 => "M&#46; Fern&#225;ndez"
                            4 => "A&#46; Garc&#237;a-Layana"
                            5 => "P&#46; Gili"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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        "texto" => "<p id="par0310" class="elsevierStylePara elsevierViewall">We would like to thank Dr&#46; Cristina Tural Ll&#224;cher&#44; Head of the Internal Medicine Department of the Germans Trias i Pujol University Hospital&#44; for her valuable contribution to the preparation and review of this document&#46; Her help has been key to the development of this work&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">We would also like to acknowledge the valuable collaboration of Gustavo Regalado&#44; professional illustrator&#44; for the images created for this manuscript&#46;</p>"
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Article information
ISSN: 23870206
Original language: English
DOI:10.1016/j.medcle.2024.07.003
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