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Esteban-Ortega, M. Steiner, I. García-Lozano, I. Thuissard-Vasallo, M. Moriche-Carretero, S. Muñoz-Fernández" "autores" => array:7 [ 0 => array:3 [ "nombre" => "M.M." "apellidos" => "Esteban-Ortega" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 1 => array:4 [ "nombre" => "M." "apellidos" => "Steiner" "email" => array:1 [ 0 => "martina.steiner@salud.madrid.org" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "García-Lozano" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "I." "apellidos" => "Thuissard-Vasallo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Moriche-Carretero" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "S." "apellidos" => "Muñoz-Fernández" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 6 => array:1 [ "colaborador" => "from the Grosor Coroideo en Espondilitis Anquilosante (COnTEST) Group" ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Sección de Oftalmología, Hospital Universitario Infanta Sofía, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina, Facultad de Ciencias Biomédicas, Universidad Europea, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Sección de Reumatología, Hospital Universitario Infanta Sofía, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Reproducibilidad de la medición manual del grosor coroideo utilizando la tomografía de coherencia óptica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1551 "Ancho" => 2510 "Tamanyo" => 345040 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Scatterplot showing the comparison of measurements of all observers.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The choroid is the most vascularized layer of the eye. Choroid is located between the sclera and the retina, separated from the retina by the Bruch’s membrane, which lies in contact with the retinal pigment epithelium (RPE). The high vascular component of the choroid makes this layer susceptible to inflammation in multisystemic diseases.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Until recently, indocyanine green angiography was the main tool available to visualize the choroidal vessels. Choroidal vascular disease results in changes in choroidal thickness (CT), which cannot be measured by angiography. Optical coherence tomography (OCT) is a novel method, which provides high-definition images of the choroid. Ophthalmologists can measure CT with OCT in a non-invasive and easy way.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Systemic diseases with vascular involvement may modify CT.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Some authors have found increased CT in patients with active inflammatory diseases such as, ankylosing spondylitis (AS), Behçet disease, sarcoidosis.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–9</span></a> Current literature has demonstrated that CT may change depending on the level of inflammation. CT increases during the active phase of the disease, decreases during remission.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This pattern is observed in lupus, systemic sclerosis, Behçet disease or AS. However, repeated flares and long-term disease may thin the choroid, as a result of prolonged insult to the microvasculature and subsequent atrophy, especially in the diseases with vascular involvement. The injury can be initiated by the induction of immune activation and the generation of autoantibodies and activated cellular immunity. The vascular injury activates platelet and coagulation pathways, which result in vascular microthrombosis. The resulting vasculopathy is associated with intimal hyperplasia in the small arterioles, and the ensuing luminal narrowing results in tissue hypoxia and chronic ischemia. Abnormal production of numerous cytokines, chemokines and other inflammatory mediators cause the inflammation and proliferation, which lead to the tissue destruction. Some other situations may also influence CT, like the circadian rhythm, the menstrual cycle or pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">OCT measurements might be influenced by the observer. Reliability of different observers’ manual measurements is relevant for patients with long term follow up and for standardization of multicenter research. However, there are few studies on the correlation of several observers.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,14–16</span></a> The aim of this study was to assess the inter-observer and intra-observer variability of the manual measurements of subfoveal CT.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Participants</span><p id="par0030" class="elsevierStylePara elsevierViewall">This cross-sectional study compared CT of 10 AS patients without eye inflammation and 11 healthy subjects matched by sex and age group (18–45 years and 45–60 years). The age of the participants ranged between 18–60 years. Patients with AS were recruited in rheumatology department of Hospital Universitario Infanta Sofía (HUIS) in Madrid. All patients met modified New York criteria and were naïve for biological therapy.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Concomitant medications permitted at the time of enrollment were nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate or sulfasalazine, but not biological treatment. Healthy subjects were staff from the HUIS. Patients with history of other disease than AS, with proven influence on CT were excluded from the study.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> AS patients with former or present history of ocular involvement were also excluded from the study, to avoid a local effect of inflammation on CT. All the subjects included in the study underwent a preliminary auto refractometer and slit lamp examination to rule out any ocular alterations that could interfere with the results.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> Patients with spherical equivalent value greater than ±4.0 diopters, coexisting ocular disease such as glaucoma, ocular hypertension or previous history of ocular trauma, surgery, retinopathy, acute or chronic uveitis and optic neuropathy were rejected from the study.</p><p id="par0035" class="elsevierStylePara elsevierViewall">All the investigators acted in accordance with the principles of the Declaration of Helsinki. Written consent was obtained from all participants. The study was approved by the appropriate institutional review boards (Code STE-INF-2017-01).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Observers</span><p id="par0040" class="elsevierStylePara elsevierViewall">Nine ophthalmologists (observers) from 6 different hospitals performed the measurements. All observers had a minimum of four years’ experience in this technique.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The observers were scheduled at different time points to avoid influence from each other. Each observer recorded the 40 measurements in a Case Report Form (CRF), which was eventually submitted to the principal investigator. Data were later entered into an anonymized, specifically designed database. Two ophthalmologists were selected to perform an intra-observer study.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Anonymized OCT images were captured by 2 ophthalmologists experienced in the technique. One image per eye was taken. All 9 observers performed the measurements on the pre-taken images. For the intraobserver analysis the 2 observers read the images once and one month later for the second time.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The OCT images corresponding to patients and healthy subjects were duly interspersed when it came to the readings.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Measurements</span><p id="par0060" class="elsevierStylePara elsevierViewall">For our study, we used RTVue OCT (RT 100. Optovue™) with Spectral Domain (SD-OCT) (Fig. 1).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">In SD-OCT system, the information of the A-scan is acquired by a charge-coupled device (CCD) camera simultaneously, with an acquisition rate of up to 40 000 A-scans per second.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The CT was measured using the cross-line scan, which was averaged, and with the chorioretinal setting which places the highest level of the signal in the lower part of the screen, resulting in a better visualization of the choroid. The subfoveal CT was defined as the distance from the RPE (its hyperreflective line) to the inner limit of sclera-choroidal junction which corresponds to the hyperfluorescent surface. This measurement is widely used by different authors and is a non-invasive, easy-to-perform, reproducible technique that does not require mydriatic drugs.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20–22</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Sample size</span><p id="par0075" class="elsevierStylePara elsevierViewall">On an assumption of an anticipated agreement between observers, intra-class correlation coefficient (ICC) of 0.8 and an acceptable 95% confidence interval (CI) width of 0.25, the minimum sample size estimated was 33 eyes.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">A descriptive analysis was carried out using the absolute (n) and relative (%) frequency to express qualitative variables. Quantitative variables were expressed as the mean and standard deviation (SD) or median and interquartile range [IQR] depending on the normal or non-normal distribution of the variables, respectively, after applying the appropriate normality test. The correlation coefficient of Pearson was used to analyze correlation between the measurements of the different experts. The level of agreement between the results obtained by the observers was evaluated with ICC and confidence interval (CI), as recommended.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Values above 0.90 were considered as having a very good correlation; values from 0.71 to 0.90 as having a good correlation; values from 0.51 to 0.70 as moderate; between 0.31 and 0.50 as mediocre; and if the values are less than 0.31 the correlation is poor or null. <span class="elsevierStyleItalic">P</span>-values <.05 for ICC provide strong evidence against the null hypothesis. Therefore, <span class="elsevierStyleItalic">P</span>-values <.05 suggest that the agreement is not due to chance. ICC estimates and their 95% CI were calculated using SPSS statistical package version 21 (IBM Corp., Armonk, NY, USA) based on a mean-rating (k = 10), absolute-agreement, 2-way random-effects model.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Demographic data</span><p id="par0085" class="elsevierStylePara elsevierViewall">Twenty-one subjects participated in the study. Eleven of the 21 subjects (52%) were male. Median age was 48 [38–54] years (range, 28–60). Eleven were healthy individuals and 10 were AS patients aged between 18–60 years. Five patients (50%) presented low disease activity and the others five patients (50%) presented high disease activity of AS.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Therefore, 42 images were initially obtained for measurements. Two images were excluded due to an image capturing error, leaving a total of 40 images with enough quality for measurements. Autorefractometer examination revealed that all participants in the study were in range ±2.0 diopters and no ocular pathological findings were described on biomicroscopic examination in any participant.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Overall measurement results</span><p id="par0095" class="elsevierStylePara elsevierViewall">The mean subfoveal CT was 364.9 ± 85.1 µm (range, 170–572). The mean CT was 374.2 ± 87.8 µm (range 170–562) in the right eye and 354.7 ± 81.0 µm (range, 205–572) in the left eye. Subfoveal CT showed a high correlation between both eyes (r = 0.751; <span class="elsevierStyleItalic">P</span> < .001 [Fig. 2]).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Inter-observer reproducibility</span><p id="par0100" class="elsevierStylePara elsevierViewall">The reproducibility measured using the ICC method in all subjects was 0.823 (CI 95%, 0.749–0.888, <span class="elsevierStyleItalic">P</span> < .001 [Fig. 3]). When the patient and healthy subjects’ groups were analyzed separately, the ICC in healthy subjects was 0.823 (CI 95%, 0.718–0.908, <span class="elsevierStyleItalic">P</span> < .001) and in the patients’ group was 0.825 (CI 95%, 0.711–0.917, <span class="elsevierStyleItalic">P</span> < .001). Comparison of measurements of all observers are displayed in [Fig. 4].</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Intra-observer reproducibility</span><p id="par0105" class="elsevierStylePara elsevierViewall">The intra-observer ICC of ophthalmologist 1 was 0.885 (CI 95%, 0.783–0.939, <span class="elsevierStyleItalic">P</span> < .001). The intra-observer ICC of ophthalmologist 2 was 0.925 (CI 95%, 0.859–0.960, <span class="elsevierStyleItalic">P</span> < .001).</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">In this study, a good agreement was found among different observers with manual measurements of OCT. Also, a good agreement was found in the intra-observer test. One patient may have sequential measurements by one or different observers during his/her disease follow-up. Concerns existed about the validity of different observers’ and serial measurements of OCT.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Over the last decades, CT measurement has been proposed and evaluated as a potential inflammatory marker for inflammatory diseases.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> AS is an inflammatory disease characterized by flares associated with increased pain. Eventually, the inflammation caused by the disease affects axial and peripheral joints and flares may lead to the progressive stiffening of the spine.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Approximately 20% of patients with AS also experience eye inflammation, which is the most common extra-articular manifestation of the disease.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Acute inflammatory activity is particularly difficult to quantify in AS. The accuracy of acute-phase reactants is limited for this purpose. Acute phase reactants do not correlate well with clinical activity or radiological progression.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Our research group has a special interest in evaluating other biomarkers for the evaluation of inflammatory activity in patients with AS. CT is a promising biomarker in this area. Patients with AS were chosen for this study because the CT of patients with AS has been suggested to be thicker than in healthy subjects.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,26</span></a> Healthy subjects were included to demonstrate a good concordance in potentially different populations. We decided to include both populations under the assumption that AS patients and healthy subjects may have different CT.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Kola et al. first reported significantly thicker CT in patients with AS than in a set of healthy subjects.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The patients included in that study were undergoing diverse treatments, such as NSAIDs, sulfasalazine, and anti-tumor necrosis factor [TNF]-α therapy. However, healthy subjects were not matched according to CT cofactors, such as age and sex. Karkucak et al. compared CT in 31 patients with active AS and in 24 healthy subjects. CT was thicker in the patient group, although the difference was not statistically significant.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Importantly, and differently from our study, OCT evaluations in both studies were performed by only one researcher. More observers include a higher level of uncertainty. One of the original aspects of our is that we show that even with a high number of observers, OCT is a valuable tool for evaluating CT. To support multicenter studies on this subject, it is essential to demine the good correlation of the measurements between multiple observers.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Hereby, we demonstrate that the agreement among different observers is good, and only small differences are observed. This good agreement is maintained even when evaluating 2 different populations (healthy subjects and patients with AS). According ISO guidelines, the bias of the measurement method is measured by the displacement of the average of results from a large number of different laboratories all using the same method.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Following this definition, we believe that having more observers provide more accurate and real data about the potential bias of the measurement method that only 2 observers. We demonstrate that even with a large number of observers, the bias is small. Also, serial measurements from the same observer yield small differences.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Currently, OCT is used by ophthalmologists to quantify CT in the clinical setting. Reproduction of the same result by different observers may be challenging, if compared with automatic and semi-automatic devices. Anatomical variations, image quality and the difficulty in distinguishing the sclera-choroidal junction—the border together with the RPE layer that defines the thickness—contribute to the potential variability.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The high reproducibility indexes in this study suggests that OCT is a valid method for serial measurements performed by 1 or different observers. A few previous studies with only 2 trained observers have shown a good correlation (ICC, 0.93–0.99).<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,21,29,30</span></a> The high diversity of observers in our study may explain that the ICC in our study was slightly lower, when compared to the previous studies. The only study with >2 observers was performed by Ikuno et al. Six observers measured 24 eyes and found ICC of 0.912 (95% CI, 0.835–0.958).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In our study, there were more observers (9) and more eyes (40). This high variability very likely increases the probability of disagreement. The more observers carrying out measurements of the same patient, the more differences will be found. Therefore, caution should be exercised when serial measurements of patients are made in departments with several ophthalmologists, and in multi-center research studies. Still, external and internal validity of manual measurements with manual OCT is high enough to ensure patients’ care.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Clinicians may wonder if patients with systemic diseases should have performed OCT in both eyes, or if 1 eye is enough. In our study, we found a high correlation between right eye and left eye, as previously described.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> These results suggest that measurement of only 1 eye per patient might be enough in some circumstances.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Limitations of this study includes the absence of a full parallel intra-observer study. However, the aim of the study was the external validity rather than internal validity. The good intra-observer indexes in 2 observers are enough to demonstrate that serial measurements are reliable. Although the ICC was good, small differences remained among some of the observers. Prior training may be useful to improve concordance.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion, manual measurements of CT had good correlation both among several observers and among serial measurements performed by the same observer. This study supports the use of manual measurement of CT using OCT as a valid tool in the clinical setting and for multi-center research studies.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Ethical approval</span><p id="par0155" class="elsevierStylePara elsevierViewall">All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">The present article is part of the COnTEST Rheumatology and Ophthalmology Project. COnTEST has financial support from the <span class="elsevierStyleGrantSponsor" id="gs0005">Madrid Rheumatologist Society</span> [Grant <span class="elsevierStyleGrantNumber" refid="gs0005">SORCOM/2017</span>], <span class="elsevierStyleGrantSponsor" id="gs0010">European University</span> [Grant <span class="elsevierStyleGrantNumber" refid="gs0010">2017/UEM12</span>] and from the <span class="elsevierStyleGrantSponsor" id="gs0015">Spanish Foundation of Rheumatology</span> [Grant <span class="elsevierStyleGrantNumber" refid="gs0015">FER/2018</span>].</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1371325" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1260312" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1371326" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1260313" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Participants" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Observers" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Measurements" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Sample size" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Demographic data" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Overall measurement results" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Inter-observer reproducibility" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Intra-observer reproducibility" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Ethical approval" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of interest" ] 11 => array:2 [ "identificador" => "xack476237" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-12-25" "fechaAceptado" => "2020-03-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1260312" "palabras" => array:4 [ 0 => "Choroidal thickness" 1 => "Inter-observador study" 2 => "Optical coherence tomography" 3 => "Intra-class correlación coefficient" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1260313" "palabras" => array:4 [ 0 => "Grosor coroideo" 1 => "Estudio interobservador" 2 => "Tomografía de coherencia óptica" 3 => "Coeficiente de correlación intraclase" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Spectral-domain optical coherence tomography (SD-OCT) is the most useful tool to measure choroidal thickness (CT). CT may be increased in ocular and systemic diseases. However, there are concerns relating reproducibility and external validity of OCT.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to assess the inter-observer and intra-observer variability of manual OCT measurements.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">CT was manually measured in the central choroid of 40 eyes from 21 subjects (11 healthy and 10 with ankylosing spondylitis) using RTVue-100 OCT (Optovue). Measurements were performed by 9 independent ophthalmologists from 6 different centers. To assess the inter-observer variability, the intra-class correlation coefficient (ICC) method was calculated. Also, intra-observer variability was assessed in 2 of the ophthalmologists.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The mean subfoveal CT was 364.9 ± 85.1 µm (range, 170–572). The inter-observer ICC was 0.823 (CI 95%, 0.749–0.888, <span class="elsevierStyleItalic">P</span> < .001). The intra-observer ICCs were 0.885 (CI 95%, 0.783–0.939, <span class="elsevierStyleItalic">P</span> < .001) and 0.925 (CI 95%, 0.859–0.960, <span class="elsevierStyleItalic">P</span> < .001).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">In this study, manual measurements of CT with OCT showed a good concordance. These results suggest that manual OCT is a valid tool for multicenter studies.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La tomografía de coherencia óptica de dominio espectral (SD-OCT) es la herramienta de mayor utilidad para medir el grosor coroideo (GC). El GC puede estar aumentado tanto en las enfermedades oftalmológicas como en las sistémicas. No obstante, existen ciertas inquietudes en relación con la reproducibilidad y la validez externa de la OCT. El objetivo de este estudio fue determinar la variabilidad inter-observador e intra-observador de la medición manual de la OCT.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">El GC fue medido de manera manual en la región central en 40 ojos de 21 sujetos (11 sanos y 10 con espondilitis anquilosante) utilizando RTVue-100 OCT (Optovue). Las mediciones fueron obtenidas por 9 oftalmólogos independientes de 6 centros diferentes. Para determinar la variabilidad inter-observador se utilizó el cálculo del coeficiente de correlación intraclase (CCI). También la variabilidad intra-observador fue determinada en 2 de los oftalmólogos.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La media del GC subfoveal fue de 364.9 ± 85.1 µm (rango, 170–572). El CCI inter-observador fue 0.823 (IC 95%, 0.749−0.888, <span class="elsevierStyleItalic">P</span> < .001). El CCI intra-observador fue 0.885 (IC 95%, 0.783−0.939, <span class="elsevierStyleItalic">P</span> < .001) y 0.925 (IC 95%, 0.859−0.960, <span class="elsevierStyleItalic">P</span> < .001).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">En este estudio la medición manual del GC ha demostrado Buena concordancia. Los resultados sugieren que la medición manual con la OCT es un método válido para los estudios multicéntricos.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Esteban-Ortega MM, Steiner M, García-Lozano I, Thuissard-Vasallo I, Moriche-Carretero M, Muñoz-Fernández S. Reproducibilidad de la medición manual del grosor coroideo utilizando la tomografía de coherencia óptica. Arch Soc Esp Oftalmol. 2020. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.oftal.2020.03.013">https://doi.org/10.1016/j.oftal.2020.03.013</span></p>" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">These authors also contributed to this work.</p>" "identificador" => "fn0005" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 783 "Ancho" => 1500 "Tamanyo" => 79608 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cross-line scanner measurement of the choroid using SD-OCT.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1070 "Ancho" => 1510 "Tamanyo" => 71532 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Scatterplot showing the lineal correlation of subfoveal choroidal thickness in both eyes and measured with SD-OCT.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1402 "Ancho" => 1425 "Tamanyo" => 127353 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Scatterplot showing the measurements of subfoveal choroidal thickness. Each point represents the measurement of a single eye performed by a pair of observers (i.e., observer 1 and observer 2; observer 1 and observer 3; observer 1 and observer 4, etc.).</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1551 "Ancho" => 2510 "Tamanyo" => 345040 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Scatterplot showing the comparison of measurements of all observers.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. 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