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Original article
Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection
Disminución de la densidad vascular retiniana en pacientes con COVID-19 y niveles elevados de dímero D durante la fase aguda de la infección
Noemi Guemes-Villahoza,
Corresponding author
noemiguemes@gmail.com

Corresponding author.
, Barbara Burgos-Blascoa, Beatriz Vidal-Villegasa, Juan Donate-Lópezb, Francisco Javier Martín-Sánchezc, Jesús Porta-Etessamd, Lorenzo López-Guajardob, José Luis R. Martíne, Juan Jorge González-Armengolc, Julián García-Feijoóf
a Servicio de Oftalmología, Hospital Clínico San Carlos; Instituto de investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
b Servicio de Oftalmología, Hospital Clínico San Carlos; Instituto de investigación sanitaria del Hospital Clínico San Carlos (IdISSC); Universidad Complutense de Madrid (UCM), Madrid, Spain
c Servicio de Urgencias, Hospital Clínico San Carlos, Instituto de investigación sanitaria del Hospital Clínico San Carlos (IdiSCC), Universidad Complutense de Madrid, Spain
d Servicio de Neurología, Hospital Clínico San Carlos, Instituto de investigación sanitaria del Hospital Clínico San Carlos (IdiSCC), Universidad Complutense de Madrid, Spain
e Medical Research Consultant, Simplifying Research Institute, Spain
f Profesor y jefe de servicio de Oftalmología, Hospital Clínico San Carlos; Departamento de Inmunología, Oftalmología y ORL, Facultad de Medicina, Universidad Complutense de Madrid (UCM); IdISSC, Madrid, Spain
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        "titulo" => "Disminuci&#243;n de la densidad vascular retiniana en pacientes con COVID-19 y niveles elevados de d&#237;mero D durante la fase aguda de la infecci&#243;n"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; OCTA of the macular region&#44; showing an angiogram of the retinal circulation in the superficial capillary plexus&#46; The image depicts the retinal arteries and veins within the macular region in a binarized OCTA image&#44; which represents the blood vessels in white color&#46; The central area devoid of vessels represents the foveal avascular zone &#40;&#42;&#41;&#46; &#40;B&#41; Color image with ETDRS sectors&#44; depicting the 9 sectors of the ETDRS grid in the macular region&#46; The fovea is represented by the central circle &#40;C&#41;&#46; Both inner &#40;I&#41; and outer &#40;O&#41; rings are further subdivided into superior &#40;S&#41;&#44; nasal &#40;N&#41;&#44; inferior &#40;I&#41; and temporal &#40;T&#41; region&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">An outbreak of a novel coronavirus named severe acute respiratory syndrome coronavirus &#8211; 2 &#40;SARS-CoV-2&#41; was reported in Wuhan&#44; Hubei Province &#40;China&#41; in December 2019&#46; This virus causes the coronavirus disease 2019 &#40;COVID-19&#41;&#44; that is making an extraordinary impact worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">COVID-19 has shown several clinical manifestations at respiratory&#44; gastrointestinal and neurological levels&#44; among others&#46; SARS-CoV-2 infection has also been related to inflammatory and coagulation abnormalities&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">2&#44;3</span></a> The pathophysiology of these complications is not fully understood&#44; as well&#44; as is the extent of these after the acute phase of the infection&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; there are no previous reports in the medical literature that depict and quantify the short-term small vessel alterations in COVID-19 patients&#46; Given the current situation of SARS-CoV-2 pandemic&#44; identifying retinal vascular changes that are associated with clinical and laboratory parameters that carry an increased risk of systemic complications secondary to infection has relevant implications in the follow-up of these patients and identification of possible short- and long-term sequels of COVID-19&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">To this end&#44; the retina is a relatively accessible organ to evaluate and quantify these microvascular changes via direct examination of blood vessels&#46; Optical coherence tomography angiography &#40;OCTA&#41; is a novel&#44; rapid&#44; and non-invasive technique that generates a three-dimensional angiogram of the retina&#44; without the need for a contrast agent&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> Several studies have evaluated by OCTA the clinical and subclinical retinal microvascular changes associated with systemic diseases&#44; such as diabetes mellitus&#44; systemic arterial hypertension and infectious diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">5&#8211;8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The main purpose of this study is to describe retinal vessel density and perfusion in patients with COVID-19 using OCTA and to investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0030" class="elsevierStylePara elsevierViewall">This is a case series study with cross-sectional analysis that was carried out in Hospital Clinico San Carlos &#40;HCSC&#41;&#44; a tertiary&#44; multispecialty metropolitan <span class="elsevierStyleItalic">teaching hospital</span> located in Madrid&#44; Spain&#46; The study was approved by the Clinical Research Ethics Committee and was conducted in accordance with the Helsinki Declaration&#46; Written informed consent was obtained from all patients&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patient selection</span><p id="par0035" class="elsevierStylePara elsevierViewall">We selected COVID-19 patients attended in Emergency Department &#40;ED&#41; from March 23 to March 29&#44; 2020&#46; The inclusion criteria were&#58; age 18&#8211;65 years old&#44; positive reverse transcriptase&#8211;polymerase chain reaction &#40;RT-PCR&#41; test from nasopharyngeal swab for SARS-CoV-2&#44; sample blood for a laboratory test required during the clinical evaluation in acute phase of infection and written informed consent for the participation in the study&#46; Those patients with previous history of stroke or thromboembolic events&#44; concomitant ophthalmic diseases&#44; antithrombotic therapy&#44; the requirement for longer quarantine &#40;patients still admitted to COVID-19 unit or intensive care unit&#44; persistence of respiratory symptoms&#44; persistently positive PCR test&#44; close contact of laboratory-confirmed or probable COVID-19 patients after discharge&#41;&#44; unable to attend the hospital&#44; or did not consent to participate in the study were excluded&#46; The concomitant ophthalmic diseases excluded were high myopia &#40;&#62;6 diopters&#41;&#44; macular disorders&#44; optic nerve head disease&#44; retinal vascular disorders&#44; previous ocular surgery other than uncomplicated cataract extraction and intraocular lens implantation performed more than 6 months before enrollment and media opacity that affected examination&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ophthalmologic examination</span><p id="par0040" class="elsevierStylePara elsevierViewall">Every patient underwent an ophthalmologic examination that included slit-lamp exam&#44; fundus examination and optical coherence tomography angiography &#40;OCTA&#41; at least 4 weeks after being attended in the ED in order to fully comply mandatory isolation&#46; The isolation criteria according to the World Health Organization &#40;WHO&#41; is 10 days after symptom onset&#44; plus at least 3 additional days without symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> All patients underwent the examination at least 28 days after COVID-19 diagnosis&#44; thus ensuring sufficient time&#46; Moreover&#44; those patients who required a longer quarantine period according to different criteria established by the public health department were excluded&#46; All procedures followed infection control and prevention measures according to the hospital&#39;s protocol&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">OCTA images were obtained using spectral-domain OCTA Zeiss Cirrus 5000 with AngioPlex &#40;Carl Zeiss Meditec&#44; Inc&#46;&#44; Dublin&#44; CA&#44; USA&#41;&#46; Macular angiography imaging with 6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>mm scans was performed in both eyes for each subject&#46; Inclusion criteria for the acceptable signal strength &#40;SS&#41; was 6 or higher&#46; The optical microangiography-complex &#40;OMAG<span class="elsevierStyleSup">c</span>&#41; algorithm analyzed the changes in complex signals&#46; Scans were analyzed using the Cirrus OCTA software &#40;AngioPlex&#8482;&#44; version 11&#46;0&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">All OCTA scans were performed by the same trained examiner&#44; and were reviewed individually by two ophthalmologists &#40;NG and BB&#41; for quality evaluation&#44; excluding substandard scans&#46; Quantification of the vessel density &#40;VD&#41;&#44; perfusion density &#40;PD&#41;&#44; and foveal avascular zone &#40;FAZ&#41; area&#44; perimeter&#44; and morphology in the superficial capillary plexus &#40;SCP&#41; were noted&#46; The macular region was segmented according to the nine Early Treatment of Diabetic Retinopathy Study &#40;ETDRS&#41; sectors&#46; The fovea was represented by the central circle of 1<span class="elsevierStyleHsp" style=""></span>mm in diameter&#46; The inner ring had an inner diameter of 1<span class="elsevierStyleHsp" style=""></span>mm and an outer diameter of 3<span class="elsevierStyleHsp" style=""></span>mm&#44; and the outer ring had an inner diameter of 3<span class="elsevierStyleHsp" style=""></span>mm and outer diameter of 6<span class="elsevierStyleHsp" style=""></span>mm&#46; Both inner and outer rings were further subdivided into superior&#44; nasal&#44; inferior and temporal region &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1A and 2B</a>&#41;&#46; The right eye was included&#44; unless it did not meet the inclusion and exclusion criteria&#44; in which case the left eye was included&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Variables</span><p id="par0055" class="elsevierStylePara elsevierViewall">Socio-demographic data &#40;age&#44; gender and birthplace&#41;&#44; medical history &#40;arterial hypertension&#44; diabetes mellitus&#44; dyslipidemia&#44; obesity&#44; chronic respiratory and heart disease&#44; smoking&#41;&#44; clinical findings at ED presentation &#40;symptoms onset&#44; baseline oxygen saturation&#44; consolidation on chest X-ray&#44; and clinical severity according to WHO ordinal scale<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a>&#41; and laboratory tests &#40;lymphocytes count&#44; D-Dimer &#8211; DD-&#44; C-reactive protein &#8211; CRP- and lactate dehydrogenase &#8211; LDH-levels&#41; during the hospital stay were collected&#46; Regarding laboratory test&#44; we considered the highest levels documented during the hospital stay&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Continuous variables are presented as mean &#40;standard deviation &#91;SD&#93;&#41; or median &#40;interquartile range &#91;IQR&#93;&#41;&#44; as appropriate&#59; categorical variables as numbers and percentages&#46; A normality test was carried out for all variables based on their randomness&#44; variance and Kolmogorov&#8211;Smirnov test&#46; In the case of not having the possibility of parametric analysis&#44; these were carried out with non-parametric tests to relate the variables under study&#46; Macular OCTA parameters were analyzed according to hypoxemia at ED presentation and the highest values of DD&#44; LDH and CRP&#46; Laboratory data were dichotomized according to cut-off values established in reference COVID-19 studies&#46; Thus&#44; the cutoffs values were 500<span class="elsevierStyleHsp" style=""></span>ng&#47;ml for DD levels&#44; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L for CRP levels and 500<span class="elsevierStyleHsp" style=""></span>U&#47;L for LDH&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> Hypoxemia was defined as oxygen saturation<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>92&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> Comparisons among groups were made using <span class="elsevierStyleItalic">t</span>-Student for continuous variables&#46; P value for linear trend was estimated&#46; Subgroup analysis for clinical and laboratory variables was performed&#46; Statistically significant differences were considered two-side <span class="elsevierStyleItalic">p</span>-value less than 0&#46;05&#46; The sample size was not calculated as this was an exploratory study&#46; Data analysis was performed using SPSS software&#44; version 24&#46;00 &#40;IBM&#44; New Castle&#44; NY&#44; USA&#41; and STATA version 15&#46;1 &#40;Stata Corp&#46;&#44; College Station&#44; TX&#44; USA&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">The overall study population included 80 patients&#46; Of the 584 patients diagnosed with COVID-19 in the Emergency Department from March 23rd to 29th 2020&#44; 235 patients met the inclusion criteria&#46; Of those&#44; 8 patients died&#44; 49 patients were lost to follow-up after emergency department discharge&#44; 22 patients were still admitted to the COVID-19 unit&#44; 15 patients were unable to return to the hospital due to their clinical situation&#44; 12 patients still presented respiratory symptoms after discharge and 11 patients did not give consent&#46; 29 patients had concomitant ocular disorders&#44; which included&#58; high myopia &#40;5&#41;&#44; age related macular degeneration &#40;3&#41;&#44; glaucoma &#40;3&#41;&#44; previous history of central serous choroidopathy &#40;1&#41;&#44; history of bilateral pars plana vitrectomy &#40;1&#41;&#44; history of retinal vascular disorders &#40;4&#41;&#44; moderate-severe media opacities &#40;12&#41;&#46; 9 patients were excluded because the OCTA image did not meet the quality criteria &#40;signal strength&#44; loss of fixation&#44; segmentation error&#44; and motion artifacts&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> depicts the flowchart of patient selection&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Of the 80 patients included&#44; 37 &#40;46&#46;3&#37;&#41; were male&#44; mean age was 54&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;2 years&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> depicts the demographical and clinical characteristics of the patients and the laboratory results&#46; Patients were evaluated in the emergency department 7 days &#40;6&#8211;10&#41; after the onset of COVID-19 symptoms&#46; Ophthalmic examination was performed 30 days &#40;28&#8211;32&#41; after COVID-19 diagnosis&#46; Slit-lamp examination of the anterior segment and the fundus revealed the above-described ophthalmic disorders in 29 patients&#44; who were excluded from the study&#46; Funduscopic examination of the 80 patients included was otherwise unremarkable&#46; None of the patients reported decrease in vision or other remarkable ocular symptoms during the illness&#44; nor until the time of the evaluation&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Vessel density and perfusion density measurements at the SCP of the macular region were analyzed&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> depicts macular OCTA results in COVID-19 patients after the acute phase of the infection&#46; A marked difference was observed for the variable D-dimer&#46; Patients with levels of DD<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>ng&#47;ml during SARS-CoV-2 infection had a decreased of central vessel density &#40;8&#46;8 &#40;SD 4&#46;0&#41; vs 6&#46;6 &#40;SD 3&#46;6&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;013&#59; mean difference 2&#46;2&#59; 95&#37;CI 0&#46;4&#8211;3&#46;9&#41; and perfusion 19&#46;6 &#40;SD 9&#46;3&#41; vs&#46; 14&#46;7 &#40;SD 8&#46;0&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018&#59; mean difference 4&#46;9&#59; 95&#37;CI 0&#46;9&#8211;8&#46;9&#41; after the acute phase of COVID-19&#46; They also showed a significant decrease of perfusion in the temporal inner sector of the macula &#40;40&#46;3 &#40;SD 5&#46;5&#41; vs&#46; 36&#46;7 &#40;SD 9&#46;5&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;033&#59; mean difference 3&#46;6&#59; 95&#37;CI 0&#46;3&#8211;6&#46;9&#41; and a tendency in the vessel density in that sector &#40;17&#46;0 &#40;SD 2&#46;0&#41; vs&#46; 15&#46;7 &#40;SD 3&#46;8&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;053&#59; mean difference 1&#46;3&#59; 95&#37;CI 0&#46;0&#8211;2&#46;6&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> represents OCTA parameters according to DD levels&#46; Other OCTA parameters&#44; including FAZ&#44; showed no differences&#46; Blood oxygen saturation levels did not reveal significant differences&#46; The subgroups analysis according to the rest of laboratory parameters &#40;CRP and LDH&#41; did not show a significant difference in OCTA values&#46; Furthermore&#44; no differences were found in patients regarding clinical severity&#44; presence of consolidation on chest x-ray nor comorbidities&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Although the main clinical manifestations of COVID-19 involve respiratory and gastrointestinal symptoms&#44; there is also evidence of thromboembolic complications and blood coagulation disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> D-Dimer elevation&#44; a marker of thrombus formation&#44; has been reported to be one of the most frequent laboratory findings noted in hospitalized COVID-19 patients&#44; representing an independent predictor of hospital mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13&#44;14</span></a> Our results revealed that patients with an increased DD&#44; and therefore&#44; a prothrombotic state during the acute phase of the infection&#44; showed lower macular vessel density and perfusion in certain OCTA parameters after the infection has resolved&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Retinal vasculature may be affected by SARS-CoV-2 infection through different mechanisms&#46; The fact that the retina is one of the highest energy-consuming tissues in the body&#44; turns it into a particularly vulnerable tissue to ischemia&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a> Retinal vascular disorders has been demonstrated to be associated with systemic coagulopathies and prothrombotic states&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">16&#44;17</span></a> In addition&#44; the retinal vasculature endothelium may be also susceptible to the direct damage by SARS-CoV-2&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a> Since there is evidence of the presence of angiotensin-converting enzyme 2 &#40;ACE2&#41;&#44; a functional receptor of SARS-CoV-2&#44; in arterial and venous endothelial cells&#44; vascular damage at this level seems feasible&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> Therefore&#44; the retinal vasculature might be altered by a conjunction of events that include thromboembolisms&#44; a hypercoagulable state&#44; hypoxia and endothelial cell dysfunction&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Since the eye offers a readily accessible window to evaluate subclinical and clinical retinal vasculature changes&#44; it seems meaningful to evaluate and quantify through OCTA the retinal involvement related to COVID-19&#46; OCTA has demonstrated to be very useful in the study of other systemic diseases that associate retinal vascular disorders&#44; such as diabetes mellitus and arterial hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">20&#44;21</span></a> Donati et al&#46; found that the retinal vascular density showed pathological modifications between healthy subjects and hypertensive patients&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> These findings suggested that OCTA may identify pathological markers of an early vascular damage&#44; providing a rationale for retinal vasculature evaluation by OCTA in patients with recently resolved COVID-19&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Our results show a decrease in macular vessel density in patients with higher D-dimer values&#46; This suggests that SARS-CoV-2 may produce subclinical changes at the level of the retinal vasculature&#44; probably related to the potential prothrombotic action and the hypercoagulable state induced by SARS-CoV-2 infection&#46; Since the retinal microvasculature shares many morphological and physiological properties with the vasculature of other organs such as the brain&#44; the kidney and the coronary arteries&#44; we could hypothesize that these results could be reflected in other vital organs&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">COVID-19 patients have shown laboratory abnormalities in other parameters despite D-Dimer&#44; such as a decrease in lymphocytes and platelet count&#44; increased CRP and elevated fibrinogen and ferritin concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> However&#44; we have not found a correlation between OCTA parameters and these abnormalities&#46; The fact that inflammatory laboratory parameters such as CRP had not shown differences in retinal vessel density and perfusion&#44; and one coagulation parameter&#44; D-dimer&#44; had&#44; raises the hypothesis that the underlying physiopathology of these retinal findings may have a thrombotic origin&#46; Moreover&#44; our study found no relationship between the clinical severity of the disease and the retinal vascular changes&#46; Therefore&#44; the microvascular involvement related to COVID-19 might depend on the procoagulant state of the patient rather than on the severity of the illness&#46; This would support the fact that subclinical thromboembolic events may occur in patients with increased D-dimer despite having a mild COVID-19&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The present study has several limitations&#46; Critically ill patients are not fully represented in our sample&#44; because some have died and others remained admitted in the hospital&#46; Since severe COVID-19 is more prone to thromboembolic events and coagulopathies&#44; evaluating these patients could yield more significant data on changes at the retinal vasculature level&#46; Furthermore&#44; patients over 65 years old were excluded from this study&#46; Firstly&#44; because these patients present a higher incidence of ophthalmic disease that could condition the results&#44; and secondly&#44; because they represent population at risk that should avoid going to hospitals unless they require emergency care during this critical situation&#46; Thus&#44; the differences found in a sample with younger patients may be less evident and therefore require a larger group to find differences&#46; On the other hand&#44; our study only evaluated OCTA parameters in the superficial capillary plexus due to the fact that the available device only provides quantitative data of the superficial plexus&#46; Consequently&#44; quantitative analyses of the intermediate and deep plexus could yield additional information in this regard&#46; Finally&#44; the assessment was performed 4 weeks after being attended in the ED&#44; in order to follow mandatory isolation&#46; It would have been interesting to have evaluated the patients in an earlier stage of the disease&#46; However&#44; the extraordinary pandemic situation&#44; the limited resources and the restrictive access of infected patients to common areas did not allow it&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In conclusion&#44; a growing body of evidence exhibits that retinal vascular changes may represent a novel biomarker&#44; reflecting the sequels of an underlying microvascular disease&#46; Our results show that OCTA can detect microvascular changes not otherwise noted on dilated clinical examination in COVID-19 patients&#46; The fact that elevated D-Dimer values during SARS-CoV-2 infection are associated with a decrease of retinal vascular density and perfusion raises the possibility of further vascular involvement in other organs besides the eye&#46; More robust studies are warranted to fully elucidate the significance of these findings&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Authors&#8217; contribution</span><p id="par0115" class="elsevierStylePara elsevierViewall">All named authors meet the International Committee of Medical Journal Editors &#40;ICMJE&#41; criteria for authorship for this article&#44; take responsibility for the integrity of the work as a whole&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethics approval</span><p id="par0120" class="elsevierStylePara elsevierViewall">The study was approved by the Clinical Research Ethics Committee of HCSC and was conducted in accordance with the Helsinki Declaration&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Consent to participate</span><p id="par0125" class="elsevierStylePara elsevierViewall">Written informed consent was obtained from all patients&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Consent for publication</span><p id="par0130" class="elsevierStylePara elsevierViewall">All authors have given their approval for this version to be published&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Availability of data and code availability</span><p id="par0135" class="elsevierStylePara elsevierViewall">Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0140" class="elsevierStylePara elsevierViewall">No funding or sponsorship was received for this study or publication of this article&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">All authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe macular vessel density and perfusion in COVID-19 patients using coherence tomography angiography &#40;OCTA&#41; and to investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional analysis conducted at the Hospital Clinico San Carlos in Madrid&#44; Spain&#46; Patients with laboratory-confirmed COVID-19 that were attended in the Emergency Department &#40;ED&#41; from March 23 to March 29&#44; 2020 were included&#46; Fundus examination and OCTA were performed 4 weeks after being attended in ED&#46; Macular OCTA parameters were analyzed and correlated with clinical &#40;severity and hypoxemia- oxygen saturation<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>92&#37;&#41; and laboratory parameters during hospital stay &#40;D-Dimer-DD&#44; lactate dehydrogenase-LDH and C-reactive protein-CRP&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">80 patients were included&#44; mean age 55&#40;SD9&#41; years old&#59; 46&#46;3&#37; male&#46; We reported macular vessel density and perfusion measurements in COVID-19 patients&#46; Those patients with D-Dimer<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>ng&#47;ml during SARS-CoV-2 infection had a decrease of central vessel density &#40;mean difference 2&#46;2&#59; 95&#37;CI 0&#46;4&#8211;3&#46;9&#41; and perfusion density &#40;mean difference 4&#46;9&#59; 95&#37;CI 0&#46;9&#8211;8&#46;9&#41; after the acute phase of COVID-19&#46; These variations of vessel density and perfusion density were not documented in patients with LDH<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; CRP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg&#47;L and hypoxemia&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">COVID-19 patients showed short-term retinal vasculature abnormalities which may be related to a prothrombotic state associated with SARS-CoV-2 infection&#46; Since the retinal microvasculature shares many morphological and physiological properties with the vasculature of other vital organs&#44; further research is needed to establish whether patients with increased D-Dimer levels require more careful assessment and follow-up after COVID-19&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la densidad vascular &#40;DV&#41; y la perfusi&#243;n vascular &#40;PV&#41; retiniana en pacientes con COVID-19 mediante una angiograf&#237;a por tomograf&#237;a de coherencia &#243;ptica &#40;OCTA&#41;&#44; e investigar si existe una correlaci&#243;n entre las anomal&#237;as vasculares de la retina y los par&#225;metros cl&#237;nicos y de laboratorio&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">An&#225;lisis transversal realizado en el Hospital Cl&#237;nico San Carlos&#44; Madrid&#46; Se incluyeron pacientes con diagn&#243;stico confirmado de COVID-19 atendidos en el Servicio de Urgencias &#40;SU&#41; del 23 al 29 de marzo del 2020&#46; Se realiz&#243; una exploraci&#243;n oftalmol&#243;gica y OCTA cuatro semanas despu&#233;s de acudir al SU&#46; Se analizaron los par&#225;metros maculares de OCTA y se correlacionaron con par&#225;metros cl&#237;nicos &#40;gravedad e hipoxemia-saturaci&#243;n de ox&#237;geno &#60; 92&#37;&#41; y de laboratorio durante la estancia hospitalaria &#40;d&#237;mero D &#91;DD&#93;&#44; lactato deshidrogenasa &#91;LDH&#93; y prote&#237;na C reactiva &#91;CRP&#93;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 80 pacientes&#44; edad media 55 &#40;DE nueve&#41; a&#241;os&#59; 46&#44;3&#37; hombres&#46; Las personas con DD &#62; 500 ng&#47;mL durante la infecci&#243;n por SARS-CoV-2 tuvieron una disminuci&#243;n de la DV central &#40;diferencia de medias 2&#44;2&#59; IC 95&#37; 0&#44;4 a 3&#44;9&#41; y PV central &#40;diferencia de medias 4&#44;9&#59; IC 95&#37; 0&#44;9 a 8&#44;9&#41; despu&#233;s de la fase aguda de COVID-19&#46; Estas variaciones no se documentaron en los pacientes con LDH &#62; &#61; 500 U&#47;L&#44; CRP &#62; &#61; 10 mg&#47;L y con hipoxemia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con COVID-19 mostraron anomal&#237;as de la vasculatura retiniana a corto plazo que pueden estar relacionadas con un estado protromb&#243;tico asociado con la infecci&#243;n por SARS-CoV-2&#46; Dado que la microvasculatura de la retina comparte muchas propiedades morfol&#243;gicas y fisiol&#243;gicas con la vasculatura de otros &#243;rganos vitales&#44; es necesario seguir investigando para determinar si los pacientes con niveles elevados de DD requieren una evaluaci&#243;n y un seguimiento m&#225;s cuidadoso&#46;</p></span>"
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                  \t\t\t\t">4 &#40;5&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>Arterial hypertension &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;25&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;7&#46;5&#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"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;26&#46;3&#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"><span class="elsevierStyleHsp" style=""></span>Obesity &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;10&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>Chronic respiratory disease &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;12&#46;5&#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"><span class="elsevierStyleHsp" style=""></span>Heart disease &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Clinical data</span></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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Time from symptoms onset&#44; days &#40;median &#91;IQR&#93;&#41;</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;0 &#40;6&#46;0&#8211;10&#46;0&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Oxygen saturation&#44; &#37; &#40;median &#91;IQR&#93;&#41;</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96 &#40;4&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Oxygen saturation</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">92&#37; &#40;n&#91;&#37;&#93;&#41;</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;8&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Chest X-ray&#44; consolidation &#40;n&#91;&#37;&#93;&#41;</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;65&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Severity by WHO &#40;n&#91;&#37;&#93;&#41;</span></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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Score 1&#8211;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;51&#46;3&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Score 3&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;18&#46;8&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Score<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;30&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Laboraroty data</span></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="elsevierStyleHsp" style=""></span>Lymphocytes<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">3</span>&#47;&#956;L &#40;median &#91;IQR&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1 &#40;0&#46;8&#8211;1&#46;4&#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"><span class="elsevierStyleHsp" style=""></span>Lymphocytes<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">3</span>&#47;&#956;L &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;36&#46;3&#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"><span class="elsevierStyleHsp" style=""></span>C-reactive protein&#44; mg&#47;dl &#40;median &#91;IQR&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;5 &#40;2&#46;1&#44; 12&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>C-reactive protein<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;31&#46;3&#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"><span class="elsevierStyleHsp" style=""></span>D-Dimer&#44; ng&#47;ml &#40;median &#91;IQR&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">613&#46;0 &#40;364&#46;0&#44; 1036&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>D-Dimer<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;60&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>LDH&#44; U&#47;L &#40;median &#91;IQR&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">615&#46;0 &#40;472&#46;0&#44; 823&#46;0&#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"><span class="elsevierStyleHsp" style=""></span>LDH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>U&#47;L &#40;<span class="elsevierStyleItalic">n</span>&#91;&#37;&#93;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51 &#40;63&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">V&#58; vascular density&#59; P&#58; perfusion&#59; FAZ&#58; Foveal avascular zone&#59; SIV&#58; vessel density of superior inner sector&#59; NIV vessel density of nasal inner sector&#59; IIV vessel density of inferior inner sector&#59; TIV&#58; vessel density of inner temporal sector&#59; SOV&#58; vessel density of superior outer sector&#59; NOV&#58; vessel density of nasal outer sector&#59; IOV&#58; vessel density of inferior outer sector&#59; TOV&#58; vessel density of temporal outer sector&#59; SIP&#58; perfusion of superior inner sector&#59; NIP&#58; perfusion of nasal inner sector&#59; IIP&#58; perfusion of inferior inner sector&#59; TIP&#58; perfusion of temporal inner sector&#59; SOP&#58; perfusion of superior outer sector&#59; NOP&#58; perfusion of nasal outer sector&#59; IOP&#58; perfusion of inferior outer sector&#59; TOP&#58; temporal outer perfusion&#59; SD&#58; standard deviation&#46;</p>"
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>80&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
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                  \t\t\t\t">Central V&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;9 &#40;4&#46;0&#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">Inner V&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;1 &#40;3&#46;4&#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">Outer V&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;5 &#40;1&#46;8&#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">Full V&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;0 &#40;2&#46;0&#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">Central P&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;7 &#40;9&#46;1&#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">Inner P&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;1 &#40;6&#46;8&#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">Outer P&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;2 &#40;4&#46;5&#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">Full P&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;5 &#40;5&#46;0&#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">FAZ area&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3 &#40;0&#46;1&#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">FAZ perimeter&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;2 &#40;0&#46;6&#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">FAZ circumference&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7 &#40;0&#46;1&#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">SIV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;4 &#40;18&#46;1&#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">NIV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;0 &#40;15&#46;1&#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">IIV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;4 &#40;2&#46;9&#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">TIV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;5 &#40;2&#46;9&#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">SOV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;4 &#40;2&#46;0&#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">NOV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;0 &#40;1&#46;8&#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">IOV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;4 &#40;2&#46;1&#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">TOV&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;1 &#40;2&#46;4&#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">SIP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;6 &#40;7&#46;5&#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">NIP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#46;0 &#40;8&#46;7&#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">IIP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;3 &#40;7&#46;5&#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">TIP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#46;8 &#40;7&#46;5&#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">SOP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;2 &#40;5&#46;3&#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">NOP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;4 &#40;4&#46;7&#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">IOP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;9 &#40;38&#46;0&#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">TOP&#44; mean &#40;SD&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;4 &#40;6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2615549.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Macular optical coherence tomography angiography results in COVID-19 PATIENTS&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:24 [
            0 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization&#46; Pneumonia of unknown cause &#8211; China&#59; 5 January 2020&#46; <a target="_blank" href="https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/">https&#58;&#47;&#47;www&#46;who&#46;int&#47;csr&#47;don&#47;05-january-2020-pneumonia-of-unkown-cause-china&#47;en&#47;</a> &#91;accessed 1&#46;10&#46;20&#93;&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome &#40;MicroCLOTS&#41;&#58; an atypical acute respiratory distress syndrome working hypothesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Ciceri"
                            1 => "L&#46; Beretta"
                            2 => "A&#46;M&#46; Scandroglio"
                            3 => "S&#46; Colombo"
                            4 => "G&#46; Landoni"
                            5 => "A&#46; Ruggeri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Crit Care Resusc J Australas Acad Crit Care Med"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coagulation abnormalities and thrombosis in patients with COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Levi"
                            1 => "J&#46; Thachil"
                            2 => "T&#46; Iba"
                            3 => "J&#46;H&#46; Levy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2352-3026(20)30145-9"
                      "Revista" => array:2 [
                        "tituloSerie" => "Lancet Haematol"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optical coherence tomography angiography&#58; a comprehensive review of current methods and clinical applications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;H&#46; Kashani"
                            1 => "C&#46;-L&#46; Chen"
                            2 => "J&#46;K&#46; Gahm"
                            3 => "F&#46; Zheng"
                            4 => "G&#46;M&#46; Richter"
                            5 => "P&#46;J&#46; Rosenfeld"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0150" class="elsevierStylePara elsevierViewall">We wish to thank investigators of COVID-19&#95;URG-HCSC Register&#58; Juan Gonz&#225;lez del Castillo&#44; Adri&#225;n Valls Carb&#243;&#44; Enrique del Toro&#44; Eduardo Cardassay&#44; Gabriel Cozar L&#243;pez&#44; Mar&#237;a del Mar Su&#225;rez-Cadenas&#44; Pablo Jerez Fern&#225;ndez&#44; Beatriz Ang&#243;s&#44; Cristina D&#237;az del Arco&#44; Esther Rodr&#237;guez Adrada&#44; Mar&#237;a Teresa Montalvo Moraleda&#44; Carolina Espejo Paeres&#44; Amanda L&#243;pez Picado&#44; Carmen Mart&#237;nez Valero&#44; Juande D&#46; Miranda&#44; David Chaparro&#44; Miguel &#193;ngel Garc&#237;a Bri&#241;&#243;n&#44; Jos&#233; Luis Fern&#225;ndez Rueda&#44; Jos&#233; M&#170; Leal Pozuelo&#44; Jos&#233; Luis Fern&#225;ndez Rueda&#44; V&#237;ctor Hern&#225;ndez Mart&#237;n-Romo&#46;</p>"
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Article information
ISSN: 23870206
Original language: English
DOI:10.1016/j.medcle.2020.12.020
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