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array:24 [ "pii" => "S2173579421001882" "issn" => "21735794" "doi" => "10.1016/j.oftale.2021.02.007" "estado" => "S300" "fechaPublicacion" => "2022-04-01" "aid" => "1947" "copyright" => "Sociedad Española de Oftalmología" "copyrightAnyo" => "2021" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2022;97:191-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0365669121002306" "issn" => "03656691" "doi" => "10.1016/j.oftal.2021.02.006" "estado" => "S300" "fechaPublicacion" => "2022-04-01" "aid" => "1947" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2022;97:191-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo original</span>" "titulo" => "Resultados de vida real en el tratamiento de la degeneración macular asociada a la edad neovascular con terapia anti-VEGF. 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Analysis of 122 patients from a single centre" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1278 "Ancho" => 2175 "Tamanyo" => 131096 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Fármacos utilizados inicialmente (primer tratamiento) y en los cambios de tratamiento (segundo tratamiento, tercer tratamiento). Ranibizumab fue el fármaco que con mayor frecuencia se utilizó como primera opción terapéutica. El cambio más habitual fue pasar a aflibercept.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Giralt-Peret, A. 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Fernández-Vigo, B. Burgos-Blasco, C. Calvo-González, M.J. Escobar, H. Shi, M. Jiménez-Santos, A. Valverde-Megías, J. Reche-Frutos, L. López-Guajardo, J. Donate-López" "autores" => array:10 [ 0 => array:2 [ "nombre" => "J.I." "apellidos" => "Fernández-Vigo" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Burgos-Blasco" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Calvo-González" ] 3 => array:2 [ "nombre" => "M.J." "apellidos" => "Escobar" ] 4 => array:2 [ "nombre" => "H." "apellidos" => "Shi" ] 5 => array:2 [ "nombre" => "M." "apellidos" => "Jiménez-Santos" ] 6 => array:2 [ "nombre" => "A." "apellidos" => "Valverde-Megías" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Reche-Frutos" ] 8 => array:2 [ "nombre" => "L." "apellidos" => "López-Guajardo" ] 9 => array:2 [ "nombre" => "J." "apellidos" => "Donate-López" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S036566912100229X" "doi" => "10.1016/j.oftal.2021.02.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S036566912100229X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579421001870?idApp=UINPBA00004N" "url" => "/21735794/0000009700000004/v1_202205040553/S2173579421001870/v1_202205040553/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173579422000202" "issn" => "21735794" "doi" => "10.1016/j.oftale.2021.02.012" "estado" => "S300" "fechaPublicacion" => "2022-04-01" "aid" => "1962" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Soc Esp Oftalmol. 2022;97:184-90" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Results of the treatment of patients with exudative AMD during the COVID-19 pandemic" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "184" "paginaFinal" => "190" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Resultados del tratamiento de los pacientes con DMAE exudativa durante la pandemia por COVID-19" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1423 "Ancho" => 2508 "Tamanyo" => 183547 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Distribution of patients over time.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Arruabarrena, R. Montejano-Milner, F. de Aragón, G. Allendes, M.A. Teus" "autores" => array:5 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Arruabarrena" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Montejano-Milner" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "de Aragón" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Allendes" ] 4 => array:2 [ "nombre" => "M.A." "apellidos" => "Teus" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669121002483" "doi" => "10.1016/j.oftal.2021.02.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669121002483?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579422000202?idApp=UINPBA00004N" "url" => "/21735794/0000009700000004/v1_202205040553/S2173579422000202/v1_202205040553/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Real-life results in treating neovascular age-related macular degeneration with anti-VEGF therapy. Analysis of 122 patients from a single centre" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "191" "paginaFinal" => "197" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "L. Giralt-Peret, A. Rodríguez-Urzay, S. Pérez-Fernández, N. Martínez-Alday, A. Fonollosa-Calduch" "autores" => array:5 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Giralt-Peret" "email" => array:1 [ 0 => "lenagiralt@gmail.com" ] "referencia" => array:4 [ 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">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Rodríguez-Urzay" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "S." "apellidos" => "Pérez-Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "N." "apellidos" => "Martínez-Alday" "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" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Fonollosa-Calduch" "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">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Universitario Cruces, Barakaldo, Vizcaya, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Facultad de Medicina de la Universidad del País Vasco (UPV/EHU), Leioa, Vizcaya, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Biocruces Bizkaia Health Research Institute, Barakaldo, Vizcaya, 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" => "Resultados de vida real en el tratamiento de la degeneración macular asociada a la edad neovascular con terapia anti-VEGF. Análisis de 122 pacientes de un solo centro" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1179 "Ancho" => 2175 "Tamanyo" => 109850 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evolution of the functional (VA) and structural (CMR) response after 2 years of treatment with anti-VEGF. The axis on the left represents the CMT and the axis on the right the VA (LogMAR).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Age-related macular degeneration (AMD) is the main cause of visual loss and blindness in developed countries.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> The most important risk factor is age, although smoking, deficiency of polyunsaturated fatty acids and antioxidants, cardiovascular risk factors and different genetic polymorphisms also play a relevant role.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">AMD is currently classified according to the proposal of the <span class="elsevierStyleItalic">Age-Related Eye Disease Study</span> (AREDS) group, which defines three stages according to severity: early, intermediate and advanced. The latter form of AMD includes geographic atrophy and neovascularization.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The neovascular form constitutes 10% of the diagnoses of AMD, but represents more than 80% of the cases of severe visual acuity (VA) loss.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> Vascular endothelial growth factor (VEGF) plays a relevant role in its pathogenesis, which facilitates the growth of pathological vessels and is prone to exudation, hemorrhages and macular destructuring.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The prognosis of neovascular AMD has improved since the advent of intravitreal anti-VEGF drug treatments.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9–15</span></a> Ranibizumab was approved in 2006 based on the MARINA and ANCHOR studies,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> which demonstrated a VA gain of 8.5–11.3 letters and 6.5–7.2 letters, respectively, over 12 months administered monthly. Bevacizumab is used off-label<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> and demonstrated in the <span class="elsevierStyleItalic">Comparison of age related macular degeneration treatment trials</span> (CATT) study that both have similar efficacy in VA gain in 24 months.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Because of these results, and its low cost, its use has been promoted in public health systems.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In 2011, the efficacy of aflibercept was demonstrated in the VIEW study.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Administered every two months after an induction phase of three monthly injections, it proved to be non-inferior and clinically equivalent to ranibizumab in maintaining VA.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Pivotal clinical trials showed improvement of VA at the expense of high treatment frequency and visits. This therapeutic strategy is difficult to implement in clinical practice, and for this reason several treatment guidelines were developed.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">pro re nata</span> strategy (PRN) proposes monthly monitoring and treatment upon evidence of reactivation. It <span class="elsevierStyleItalic">treats</span> recurrence but does not <span class="elsevierStyleItalic">prevent</span> it, assuming the risk of causing irreversible structural damage.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> The <span class="elsevierStyleItalic">Treat and Extend</span> (T&E) protocol seeks to anticipate recurrences, progressively spacing the injections until the optimum is found for each patient. The visual results are better than with PRN with fewer visits.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22–25</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Although both strategies are an improvement over fixed monthly treatments, the burden of care remains very high. In addition, patients with AMD tend to be elderly and multi-pathological and for this reason tend to be undertreated.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–13,26,27</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In view of the above, the aims of the present study work are to assess the effectiveness and safety of treatment of neovascular AMD and to analyze the clinical factors related to the functional and structural prognosis of the disease in a real-life context.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">A retrospective, observational, single-centre study, which included all patients diagnosed with neovascular AMD between 2015 and 2016 who received treatment with intravitreal anti-VEGF injections and were followed up for at least two years at Cruces University Hospital (Barakaldo, Basque Country, Spain).</p><p id="par0055" class="elsevierStylePara elsevierViewall">This is a service where the Retina Section has seven retinologists who treat patients with AMD. Being a real life study, the diagnosis, the therapeutic decision and the follow-up were made at the discretion of each retinologist.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Patients previously treated with antiangiogenic agents or who dropped out of follow-up before two years, patients with other retinal diseases and those whose clinical history was incomplete were excluded.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Intravitreal treatment</span><p id="par0065" class="elsevierStylePara elsevierViewall">This study included patients treated with ranibizumab (0.5 mg/0.1 mL), bevacizumab (1.25 mg/0.1 mL) or aflibercept (2 mg/0.1 mL). The drug used as the first option was left to the retinologist’s discretion, but the protocol used was T&E. In case of unfavorable evolution, the drug was changed.</p><p id="par0070" class="elsevierStylePara elsevierViewall">All patients signed an informed consent form prior to the start of treatment. Injections were performed in a clean room under anesthesia and topical dilute iodine followed by application of topical broad-spectrum antibiotic at the end of the procedure.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data collection and variables</span><p id="par0075" class="elsevierStylePara elsevierViewall">The study data were collected in a specially designed database from the medical records registered in the computer system.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The main study variables were the mean change in VA in LogMAR and central macular thickness (CMT) by optical coherence tomography (OCT) in microns (μm) with respect to baseline at one and two years. Secondary variables were the percentage of patients who gained (one or more letters), lost (one or more letters) or maintained visual acuity (same number of letters), the number of injections and hospital visits (either for treatment or for clinical check-ups), the cost of treatments and the influence of baseline characteristics, number of injections and visits on the change in VA and CMT.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The CMT measurements in each patient were always made on the same OCT during follow-up, however, the type of OCT used was at the retinologist’s discretion. The different OCT used were: Spectralis (Heidelberg Engineering, Heidelberg, Germany) spectral-domain optical coherence tomography (SD OCT), Cirrus 6000 (Carl Zeiss Meditec, Dublin, California, USA) and Avanti RTVue XR device (Optovue, Fremont, California, USA).</p><p id="par0090" class="elsevierStylePara elsevierViewall">The study was started after approval by the Ethics Committee of the OSI Ezkerraldea-Enkarterri-Cruces (Code E20/12).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">All analyses were performed with the statistical program R: <span class="elsevierStyleItalic">A language and environment for statistical computing</span> (R Foundation for Statistical Computing, Vienna, Austria). Categorical variables were expressed as percentages. Continuous variables were expressed as mean (standard deviation) if they followed a normal distribution or median (interquartile range) otherwise.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Linear regression models were performed to analyse the change at one year, two years and total adjusting for age, sex, number of injections, number of visits and treatment and baseline. A p-value <0.05 was considered statistically significant.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">General data</span><p id="par0105" class="elsevierStylePara elsevierViewall">The study included 143 eyes of 122 patients, whose characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Of the 143, 48 (33.6%) were male and 95 (66.4%) were female. The mean age was 81.7 ± 8.39 years. Mean patient VA at diagnosis was 0.50 (0.30–0.80). The mean central macular thickness measured by OCT was 352 μm (292–426). The economic cost at two years was 336,749 euro, only in drugs, which means an expense of 1.177,5 euro per patient per year.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The mean number of injections received over two years was 13 (10.0–15.0), eight in the first year and five in the second year. Patients travelled to the hospital an average of 24 times (21.0–28.0). Of the patients, 96.5% had no complications, while five (3.5%) suffered a rupture of the retinal pigment epithelium.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Treatments used</span><p id="par0115" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, ranibizumab was administered as first treatment to 74 patients (51.7%), aflibercept to 40 (28.0%) and bevacizumab to 29 (20.3%).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">While 64 patients received a single treatment during the two years, 79 patients (55.2%) underwent a switch, with aflibercept being the most frequently chosen second treatment. Another switch and thus a third treatment was required by 17 patients.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Functional and anatomical results</span><p id="par0125" class="elsevierStylePara elsevierViewall">Mean patient VA was 0.50 (0.30–0.80) at diagnosis, 0.40 (0.20–0.70) after the first year of treatment and 0.40 (0.20–0.70) after two years. As can be seen in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>, the first year saw an improvement of 0.10 (p < 0.001) while the second year showed no improvement. At the end of the two years of treatment, 45% of the cases exhibited an improvement in VA of five letters or more, 18% remained the same and 36% worsened.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Mean CMT was 352 μm (292–426) at diagnosis, 273 μm (232–324) at one year and 257 μm (228–321) at the end of the study. The mean decrease in CMT at 2 years from baseline was 85 μm (161.5–10), a statistically significant difference (p < 0.001). The greatest decrease in CMT was observed in the first year of treatment with an improvement of 64 μm (p < 0.001), while in the second year it was 9 μm (p = 0.005).</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Predictors of structural and functional response</span><p id="par0135" class="elsevierStylePara elsevierViewall">No association was found between functional (AV) or structural (CMT) response and sex or type of initial treatment. A higher number of visits (p < 0.001) and a lower number of injections (p < 0.01) were predictors of worse structural outcome (higher BCM). Age was associated with worse functional outcome and number of visits with better visual acuity (p < 0.001).</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">The observed VA and CMT results are similar to those of other real-life studies, but with a higher number of injections received.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–13</span></a> Mean VA improved five letters from baseline, although this improvement was not statistically significant. CMT diminished significantly in the first year but not in the second one. Although the CMT is an objective of therapeutic efficacy, it does not correlate well with VA, since there are other structural parameters that influence it such as the state of the outer retina or the degree of subretinal fibrosis, which have not been evaluated in this study.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In a multicenter study<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> which assessed 11,135 patients treated with ranibizumab in PRN regimen for three years, the gain at one year was two letters, at two years was one letter and at three years two letters were lost on average.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In the AURA study,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> which evaluated the effectiveness of anti-VEGF treatment in 2227 patients from Europe, Canada and Venezuela between 2009 and 2011, treated in both PRN and T&E, baseline VA improved by 2.4 letters in the first year and 0.6 in the second year of treatment with a higher number of injections in the first year of treatment.</p><p id="par0155" class="elsevierStylePara elsevierViewall">In the LUMINOUS study,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> which looked at 3379 patients treated with ranibizumab in both PRN and T&E from different countries worldwide, the mean VA gain over one year was 3.1 letters with an average of five injections and 8.8 visits.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Wada et al.,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> who followed 295 patients treated with ranizumab according to the PRN protocol for five years, found that patients suffered a mean VA loss of 0.18 LogMAR, with a mean of 14.8 injections at five years after an increase of 0.14 LogMAR in the first year of treatment.</p><p id="par0165" class="elsevierStylePara elsevierViewall">As the most widespread treatment regimen until a few years ago, most published studies with a large sample size used PRN. However, there is increasing evidence in real-life studies that T&E treatment is more cost-effective and, therefore, preferred by most professionals. In their real-life study with 54 patients, Vardarinos et al.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> observed a gain of 5.2 letters at two years, with a mean of 12.1 injections following the T&E regimen, results comparable to those obtained in the present study.</p><p id="par0170" class="elsevierStylePara elsevierViewall">To date, there are few published studies on the effectiveness of anti-VEGF treatment in a real-life situation in Spanish centers. Oca Lázaro et al.,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> from the Ophthalmology Department of the Hospital San Pedro of Logroño, published a study that studied the functional and structural results of aflibercept treatment with a PRN regimen in 38 eyes for 12 months. They obtained excellent results with a visual gain of 13.5 letters and a mean decrease in CMT of 140 μm, results comparable to the pivotal VIEW trials.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Udaondo et al.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> from the Ophthalmology Department of the Hospital Universitari i Politècnic La Fe and Hospital de Manises in Valencia, demonstrated the effectiveness of aflibercept in 32 patients over a period of 13 months. Of the patients, 84.4% gained ≥5 letters and the CMT decreased from 383 to 249 μm after 133 months of treatment.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">In the present study, statistical analysis showed that fewer injections were associated with greater macular thickness at 2 years. Likewise, age was a factor associated with worse VA. The analysis of the association between number of visits and functional and structural outcomes has yielded initially contradictory results, since the number of visits has been associated with greater VA gain and at the same time with an increase in CMT. The number of visits could show patients who have a more aggressive disease, with worse baseline BCM, or single eyes that are followed more closely, but it also implies a greater number of treatments that would lead to more visual gain.</p><p id="par0180" class="elsevierStylePara elsevierViewall">In the knowledge of the authors, the present study has the largest sample size of those performed so far in Spain analyzing the treatment of neovascular AMD in real life, using the T&E regimen. Despite being a heterogeneous sample in terms of the treatments used, we believe that it is acceptable for drawing conclusions about clinical practice in our center and for comparing the results with other real-life studies. The fact of having included patients who underwent a change of treatment, despite making comparison with most retrospective studies difficult, adds value to the results, since this is a common strategy in clinical practice.</p><p id="par0185" class="elsevierStylePara elsevierViewall">In relation to safety, this study has shown a complication rate of 3.5%, all of which were retinal pigment epithelium (RPE) ruptures. In two years of follow-up, no cases of endophthalmitis, hemorrhage or retinal detachment occurred. The incidence of RPE rupture with intravitreal treatment varies from 1.8% to 27%, according to the literature.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32–34</span></a> A study by Vazquez-Alfageme et al.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> including 300 eyes treated with ranibizumab and 500 with aflibercept and with a mean follow-up of 34.0 ± 9.1 months, found an incidence of 2.3% and 3.2%, respectively.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Several limitations should be considered in this work. The retrospective nature, the use of different OCT in the CMT measurements and not taking into account other factors that may influence VA such as the state of the outer retina or cataract progression. The possible influence of the type of choroidal neovascularization on the prognosis of the patients and the location of the fluid in the diagnosis have not been evaluated either.</p><p id="par0195" class="elsevierStylePara elsevierViewall">In conclusion, antiangiogenic therapy in a T&E regimen has improved the functional and structural prognosis of patients in the authors’ center. However, the increasing prevalence of the disease suggests the need to optimize resources to treat the largest number of patients. Further studies are needed to evaluate real-life clinical practices and to reach a consensus on treatment guidelines to improve treatment efficiency.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0200" class="elsevierStylePara elsevierViewall">This research has not received specific support from public sector agencies, the commercial sector or non-profit organisations.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0205" class="elsevierStylePara elsevierViewall">No conflicts of interested were declared by the authors and co-authors of this work.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1700672" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1505100" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1700673" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1505101" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Intravitreal treatment" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Data collection and variables" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "General data" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatments used" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Functional and anatomical results" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Predictors of structural and functional response" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-11-18" "fechaAceptado" => "2021-02-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1505100" "palabras" => array:4 [ 0 => "Age-related macular degeneration" 1 => "Antiangiogenics" 2 => "Cohort" 3 => "Basque country" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1505101" "palabras" => array:4 [ 0 => "Degeneración macular asociada a la edad" 1 => "Antiangiogénicos" 2 => "Cohorte" 3 => "País Vasco" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The prognosis of age-related macular degeneration (AMD) has improved significantly since the advent of antiangiogenic treatments. However, several «real life» studies have shown lower number of injections and a markedly worse visual prognosis than pivotal clinical trials.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">To assess the effectiveness and safety of the treatment of neovascular AMD and analyse clinical factors related to the functional and structural prognosis in routine clinical practice.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Retrospective, observational, single-centre study that included 143 eyes of 122 patients diagnosed with neovascular AMD between the years 2015 and 2016, who received treatment with antiangiogenic drugs and were followed up for two or more years.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Visual acuity improved in 45% of patients after two years of treatment. The mean decrease in central macular thickness was 85 μm (p < 0.001) and the mean number of injections was 13. Retinal pigment epithelium rupture was present in 3.5%. Ranibizumab was the drug most used as a first option, although 79 patients (55.2%) required a change in treatment, most being switched to aflibercept. A greater number of visits (p < 0.001) and a lower number of injections (p < 0.01) were predictors of worse structural outcome. The number of visits was associated with better visual acuity (p < 0.001).</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The treatment has demonstrated its efficacy by improving visual acuity and central macular thickness. However, the number of injections performed has generally been higher than in other real-life studies.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">El pronóstico de la degeneración macular asociada a la edad (DMAE) ha mejorado significativamente desde la aparición de los tratamientos antiangiogénicos. Sin embargo, diversos estudios realizados en «vida real» han demostrado un número de inyecciones inferior y un pronóstico visual notablemente peor de los ensayos clínicos pivotales.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Valorar la efectividad y seguridad del tratamiento de la DMAE neovascular y analizar factores clínicos relacionados con el pronóstico funcional y estructural en la práctica clínica habitual.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiales y métodos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo, observacional y unicéntrico. Se incluyeron 143 ojos de 122 pacientes diagnosticados de DMAE neovascular entre los años 2015 y 2016, que recibieron tratamiento con antiangiogénicos y con un seguimiento de dos o más años.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La agudeza visual mejoró en el 45% de pacientes tras dos años de tratamiento. La disminución media de grosor macular central fue de 85 μm (p < 0,001) y el número medio de inyecciones fue de 13. Un 3,5% presentó una rotura del epitelio pigmentario. Ranibizumab fue el más utilizado como primera opción, aunque 79 pacientes (55,2%) requirieron un cambio de fármaco, pasando la mayoría a ser tratados con aflibercept. Fueron predictores de peor resultado estructural un mayor número de visitas (p < 0,001) y un menor número de inyecciones (p < 0,01). El número de visitas se asoció a mejor agudeza visual (p < 0,001).</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">El tratamiento ha demostrado su eficacia mejorando la agudeza visual y el grosor macular central. Sin embargo, el número de inyecciones realizado ha sido en general superior al de otros estudios de vida real.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Giralt-Peret L, Rodríguez-Urzay A, Pérez-Fernández S, Martínez-Alday N, Fonollosa-Calduch A. Resultados de vida real en el tratamiento de la degeneración macular asociada a la edad neovascular con terapia anti-VEGF. Análisis de 122 pacientes de un solo centro. Arch Soc Esp Oftalmol. 2022;97:191–197.</p>" ] ] "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" => 1248 "Ancho" => 2153 "Tamanyo" => 128533 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Drugs used initially (first treatment) and at treatment changes (second treatment, third treatment). Ranibizumab was the drug most frequently used as the first therapeutic option. The most common change was to aflibercept.</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" => 1179 "Ancho" => 2175 "Tamanyo" => 109850 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evolution of the functional (VA) and structural (CMR) response after 2 years of treatment with anti-VEGF. The axis on the left represents the CMT and the axis on the right the VA (LogMAR).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">n: Number of eyes; RPER: retinal pigment epithelium rupture; Treatment 1: first treatment received; Treatment 2: second treatment received; Treatment 3: third treatment received.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n = 143 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Sex</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 (33.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95 (66.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81.7 (8.39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Basal visual acuity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.50 [0.3−0.8] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Central basal macular degeneration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">352 [292−426] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140 \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>Number of injections 1 year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.00 [6.0−9.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Number of injections 2 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.00 [3.0−7.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Number of total injections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.0 [10.0−15.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Number of visits \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.0 [21.0−28.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Complications</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">138 (96.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>RPER \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (3.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Treatment 1</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">143 \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>Aflibercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Bevacizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (20.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Ranibizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 (51.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Treatment 2</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \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>Aflibercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 (81%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Bevacizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (16.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Ranibizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Treatment 3</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \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>Aflibercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (41.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Bevacizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (35.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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>Ranibizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (23.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">Started on aflibercept and changed treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">112 \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">Started on bevacizumab and changed treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (13.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">132 \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">Started on ranibizumab and changed treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (43%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">121 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2889398.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Demographic data and results obtained at two years of follow up.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">VA. visual acuity; CMT. central macular thickness.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First year of treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Second year of treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">End of treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VA enhancement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.10 [−0.30 to 0.00]<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.00 [0.00–0.20]<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0 [−0.25 to 0.20] (p = 0.1968) \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">CMT improvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−64.00 [−137.5 to (−3.00)] <a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−9.00 [−53.00 to 9.00] <a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−85.0 [−161.5 to (−10.0)] (p < 0.001) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2889399.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">p < 0.001.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">p = 0.005.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Functional and structural outcomes of antiangiogenic therapy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Degeneraciones y distrofias de la retina" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. 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