Treat-and-extend approach with aflibercept: Effects on different subtypes of age-related choroidal neovascularisation | Archivos de la Sociedad Española de Oftalmología (English Edition)

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A) Cambios funcionales y B-F) cambios anatómicos entre los diferentes tipos de neovascularizaciones secundarias a la degeneración macular exudativa asociada a la edad. Las medidas fueron tomadas en la visita basal y a los 3, 6 y 12 meses. a) Se encontraron cambios estadísticamente significativos entre neovascularizaciones de tipo 1 y tipo 2 (a) y entre neovascularizaciones de tipo 2 y tipo 3 o proliferación angiomatosa retiniana (b). DEP: desprendimiento del epitelio pigmentario; GMC: grosor macular central; logMAR: logaritmo del mínimo ángulo de resolución; MAVC: mejor agudeza visual corregida; MLE: membrana limitante externa; NVC: neovascularización; RAP: proliferación angiomatosa retiniana; ZE: zona elipsoide." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V. Castro-Navarro, E. Cervera-Taulet, J. Montero-Hernández, C. Navarro-Palop" "autores" => array:4 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Castro-Navarro" ] 1 => array:2 [ "nombre" => "E." 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Changes in VA during the entire follow-up period (from 3 to 18 months), in percentages (%)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Gallego-Pinazo, R. Dolz-Marco, M. Andreu-Fenoll, J. Farrés, L. Monclús" "autores" => array:5 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Gallego-Pinazo" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Dolz-Marco" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Andreu-Fenoll" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Farrés" ] 4 => array:2 [ "nombre" => "L." 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Castro-Navarro, E. Cervera-Taulet, J. Montero-Hernández, C. Navarro-Palop" "autores" => array:4 [ 0 => array:4 [ "nombre" => "V." "apellidos" => "Castro-Navarro" "email" => array:1 [ 0 => "veronicacastronavarro@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Cervera-Taulet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Montero-Hernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Navarro-Palop" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital General Universitario de Valencia, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Escuela de Doctorado, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estrategia «Tratar y Extender» con aflibercept: efecto en diferentes tipos de neovascularización coroidea asociada a la edad" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1448 "Ancho" => 1801 "Tamanyo" => 371897 ] ] "descripcion" => array:1 [ "en" => "Retinograph, fluorescein angiography and optical coherence tomography (OCT) of CNV type 3 or retinal angiomatous proliferation (RAP). (A)–(C) Color retinograph showing the clinical appearance of a stage 3 RAP. (B) Fluorescein angiography early stage and (C) late stage showing typical drusenoid staining and poorly defined intraretinal hyperfluorescence typical of RAP. (D)–(F) serial OCT explorations in (D) baseline visit; (E) at month 3 and (F) at month 12, showing complete resolution of intra-and subretinal fluid after Treat-and-Extend treatment with aflibercept. Note the changes in the serovascularized pigment epithelium detachment to the fibrovascularized type at the beginning and end of treatment." ] ] ] "textoCompleto" => "IntroductionThe era of multimodal image diagnostic has promoted the development of classifications for choroidal neovascularization (CNV) secondary to exudative age-related macular degeneration (AMD). Enhanced visualization also involves the discovery of anatomical characteristics that could influence visual results, such as the presence of intra- or subretinal fluid,<a class="elsevierStyleCrossRef" href="#bib0145">1</a> the integrity of the external limiting membrane (ELM) or the restoration of the ellipsoid zone (EZ).<a class="elsevierStyleCrossRefs" href="#bib0150">2–7</a>The VIEW 1 and 2<a class="elsevierStyleCrossRef" href="#bib0180">8</a> pivotal studies with aflibercept, a fusion protein derived from the combination of vascular endothelial growth factor (VEGF) receptor sequences 1 and 2, demonstrated that 2mg/0.05mL of aflibercept every 8 weeks after a charge load of 3 monthly injections is not inferior to 0.5mg/0.05mL of ranibizumab every 4 weeks. Even though the treat-and-extend (TAE) strategy has not been evaluated in the main clinical trials, it constitutes a frequently utilized treatment protocol.<a class="elsevierStyleCrossRef" href="#bib0185">9</a> Randomized studies<a class="elsevierStyleCrossRefs" href="#bib0190">10–12</a> as well as actual clinical practice<a class="elsevierStyleCrossRefs" href="#bib0205">13–15</a> demonstrated its capacity to produce visual acuity gains in treated patients up to 3 years.<a class="elsevierStyleCrossRefs" href="#bib0205">13–15</a> Even though the CNV type 1s not a crucial parameter for selecting treatment protocol or a clear prognostic signal, some of said studies have demonstrated increased benefits with this regime in type 1 neovascular membranes.<a class="elsevierStyleCrossRefs" href="#bib0205">13,14</a> Accordingly, the authors believe it would be interesting to describe the visual and anatomic results with aflibercept in a TAE regime in different types of CNV expressing in AMD.Subjects, material and methodsStudy populationA retrospective and observational study was designed for the anatomical and functional study in patients with CNV without previous treatment secondary to AMD. Patients treated for said disease in the Macula Unit of the General University Hospital of Valencia between October 1, 2014 and May 1, 2015 were included consecutively in the study provided that they fulfilled the inclusion criteria, lacked exclusion criteria and gave consent for the retrospective analysis of their data. In compliance with Act 41/2002 dated November 14, the informed consent of all patients was obtained prior to beginning treatment with aflibercept and retrospective analyses. The study was approved by the Ethics Committee of the Hospital.Inclusion criteria comprised age ≥65, best corrected visual acuity (BCVA) under 0.1 logMAR, the presence of untreated previous CNV secondary to AMD demonstrable with spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (AGF), a follow-up period of at least 12 months and the absence of other CNV causes such as polypoid vasculopathy or pathological myopia. When polypoid vasculopathy was suspected, indocyanine green angiography was performed, discarding from the study the patients in whom this was confirmed.On the basis of the findings of FAG and SD-OCT and in accordance with the classification proposed by Freund<a class="elsevierStyleCrossRef" href="#bib0220">16</a> based on the histopathological findings of Gass,<a class="elsevierStyleCrossRef" href="#bib0225">17</a> 4 subtypes of neovascular complexes were obtained. These are: (a) type 1 CNV when the neovascular process was below the retina pigment epithelium (RPE); (b) type 2 CNV when the membrane had penetrated RPE and was above it, in the subretinal space; (c) mixed CNV when the neovascular tissue was above and below the RPE, and (d) type 3 CNV or with retinal angiomatous proliferation (RAP) when neovascularization was intraretinal. RAP stages were assigned in accordance with the classification established by Yanuzzi et al. in 2001.<a class="elsevierStyleCrossRef" href="#bib0230">18</a>Procedures and interventionsThe patients received intravitreal treatment consisting of 2mg aflibercept in 0.05mL in accordance with TAE treatment protocol, carried out as follows: after charge dose consisting of 3 monthly injections, the patients were treated in all visits and evaluated as per the presence of exudative activity. If active exudation was discarded, the interval between visits was extended 2 weeks up to a maximum of 12 weeks. On the contrary, in the presence of some type of exudative activity, the interval was shortened to the minimum acceptable period between visits, i.e., 4 weeks. Exudative activity was regarded as the presence/appearance of subretinal liquid (SRL) or intraretinal liquid (IRL), increased central macular thickness (CMT) ≥100μm, and the appearance of new retinal hemorrhages or active leak in FAG. The presence of persistent pigment epithelium detachment (PED) was not regarded as a re-treatment criterion.Evaluated parametersAMD was diagnosed taking BCVA, slit lamp examination, SD-OCT and FAG (50° TopCon TRC-50IX Retinal Camera, Topcon Medical Systems, Inc., Oakland, USA, and 5mm of 10% sodium fluorescein, Fluoresceína Óculos 10%; Solution injectable, Laboratorios SERB, Brussels, Belgium). For the rest of the visits, BCVA and SD-OCT examinations were performed. Measures were recorded utilizing the data obtained at diagnostic (baseline or at first visit data), at month 3 when administering the last injection of the charge phase (visit 2) and at month 6 and 12 as of diagnostic (visits 3 and 4, respectively). BCVA was examined with the Landolt C optotypes and expressed in the logarithm of minimum angle resolution (logMAR). The quantitative and qualitative analysis of SD-OCT images was carried out in SD-OCT B-scans and volume scans obtained under pupil dilatation with 3D-TopCon (3D OCT-2000 SD-OCT, Topcon Medical Systems, Inc., Oakland, USA). Equipment software confirmed the adequate positioning of the scanner and the obtained measures. CMT and macular volume were generated automatically. ELM and ZE discontinuity was evaluated according to the methods described by Oishi,<a class="elsevierStyleCrossRef" href="#bib0170">6</a> in which a specialized technician who is not familiar with other clinical variables manually measures the length of said layers in a horizontal scanner passing through the fovea and including the region comprised between 1000 nasal microns and 1000 temporal microns from the foveal depression. For the manual measurement of the choroidal thickness at the subfoveal level and in the 500 nasal and temporal microns, the distance between the internal portion of the Bruch membrane and the chorioscleral interface was taken. The presence or absence of SRL, IRL or PED was analyzed. PED height was taken as the maximum distance between the external RPE and the innermost part of the Bruch membrane. When the PED was identified, it was classified as serovascularized or fibrovascularized subtype.Statistical analysisThe statistical analysis was carried out with the R Statistical Software (version 3.2.2 Foundation for Statistical Computing, Vienna, Austria). The descriptive analysis of data included median, standard deviation and percentages when necessary. The variables were studied utilizing the T for Student test for parametric variables, the Wilcoxon and Kruskal–Wallis test for nonparametric variables and the Chi square test. Statistical significance was defined when p<0.05.ResultsThe study included 30 eyes of 30 patients, with a median age of 78.76±6.9 years. Type 1 neovascular component was found in 11 eyes (36%), type 2 in 7 eyes (23%), mixed in 5 eyes (16%) and type 3 or RAP component in 7 eyes (23%). In the group of RAP subtype patients one eye was identified with stage 2 without PED, 3 eyes with stage 2 with PED and 3 eyes with stage 3 of the disease. The demographic and baseline characteristics of patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>After the charge dose a significant change in BCVA was identified, increasing from 0.61±0.26 logMAR to 0.44±0.32 logMAR. At month 12, after a median of 6.89±1.85 visits and 7.72±1.25 injections, final BCVA was 0.38±0.34 logMAR. Similarly, at the end of the study a significant reduction of CMT and MV was observed. Morphological parameter analysis showed that, after the charge dose, SRL at baseline visit (n=26), IRL (n=17) and serovascularized PED (n=14) diminished significantly, demonstrating stable results at month 12. ELM and ZE length increased significantly (p=0.011 and p=0.00006), starting from the baseline values of 1.687.4±214.87 and 1.527.9±298.13μm, respectively and rising to 1.821.20±104.60 and 1.766.82±127.52μm. At the end of the study, choroidal thickness was found diminished in all locations.As shown in the methods section, CNV types were classified in subtypes: (a) CNV type 1, (b) CNV type 2, (c) CNV mixed type and (d) CNV type 3 or RAP. Quantitative and qualitative SD-OCT characteristics at baseline and month 3, 6 and 12 are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Baseline differences were identified after a Kruskal–Wallis analysis. CNV type 2 exhibited the lowest BCVA (0.84±0.18 logMAR; KW=9.65; p=0.00217). The final mean number of injections (7.5±1.65 in CNV subgroup type 1; 8.71±0.76 in CNV type 2; 7.4±0.89 in mixed CNV and 7.2±0.7 in RAP) and of visits (6.6±2.17; 7.89±1.46; 5.8±1.7 and 7.14±1.57, respectively) was not different between each neovascular complex type. In what concerns functional parameters, visual acuity gain did not vary between the 4 subgroups (p>0.05) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>When analyzing anatomical changes in SD-OCT the following characteristics were obtained (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): CNV type 1 exhibited the lowest baseline CMT and the PED rate of 72%, which diminished with treatment. As regards CNV type 2, these associated mean CMT and MV values, while IRL and SRL were found to be 57 and 85%, with partial resolution after aflibercept. A noteworthy finding in this CNV type 1s lower choroidal thickness than in the other subgroups, which remained stable throughout the study. Due to the presence of the neovascular component above as well as below the RPE, the mixed type of CNV exhibited anatomic alterations typical of CNV types 1 and 2. Said subtype exhibited the largest CMT (417±129.45μm) and MV (8.71±0.64cm3) at diagnostic with IRL, SRL and PED in 80, 100 and 80% of cases, respectively. Even though the disruption of ELM and EZ in this CNV subtype was greater than in the rest, length increases were observed with treatment. Type 3 or RAP lesions, in which neovascularization begins inside the retina, showed intermediate CMT and MV values (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). External retina layers exhibited lower baseline alteration (1.828.57±179.25 and 1.644.57±370.93μm length in ELM and EZ, respectively) and their integrity increased with treatment. As occurs in CNV type 1 and mixed, a progressive reduction in choroidal thickness was observed.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionThe results obtained in the present study demonstrate that TAE treatment with aflibercept during 12 months is an effective tool in AMD. Said results show that visual gain in these patients does not initially depend on the CNV subtype. The TAE protocol is a proactive individualized treatment which at present is frequently applied.<a class="elsevierStyleCrossRefs" href="#bib0185">9,13</a> In order to obtain a fluid-free macula, TAE enables the application of an individualized treatment frequency.<a class="elsevierStyleCrossRefs" href="#bib0185">9,19</a> Randomized clinical trials with ranibizumab and bevacizumab have demonstrated their efficiency with visual gains similar to monthly regimes.<a class="elsevierStyleCrossRefs" href="#bib0190">10–12</a> Accordingly, ranibizumab groups with a mean number of injections of 8 to 10.1 in the first year and starting from mean baseline values of 60.5–62 ETDRS letters (approximately 0.5 logMAR), visual acuity gains of +8.2±10.5 (approximately 0.3 logMAR) were obtained. The present study, with a median of 7.72±1.25 injections, shows a significant BCVA improvement, from 0.61±0.26 to 0.38±0.34 logMAR.As the TAE strategy enables individual control, it has been proposed as the first choice in CNV type 1 or RAP.<a class="elsevierStyleCrossRefs" href="#bib0240">20,21</a> In the present study the patients were grouped on the basis of CNV type by means of a multimodal analysis. Despite the limitation of the small number of patients, study data demonstrate that said therapeutic regime is effective for all groups at 12 months. After a similar mean number of injections and visits, BCVA in the last visit improved up to 0.36; 0.52; 0.3 and 0.3 logMAR in CNV type 1, type 2, mixed and type 3 or RAP, respectively.Even though the present study is based on usual clinical practice, it includes baseline characteristics and visual gains similar to those of clinical trials and matching other retrospective studies. Similar or worse baseline visual values exhibited visual gains similar to those of the present study, in the area of 10 EDTRS letters.<a class="elsevierStyleCrossRefs" href="#bib0205">13,15</a> However, when starting from a higher visual acuity, it tends to remain stable.<a class="elsevierStyleCrossRef" href="#bib0250">22</a> Mrejen et al.<a class="elsevierStyleCrossRef" href="#bib0205">13</a> assessed TAE in different lesions. Said study, with a mean number of annual injections similar to those of the present study (8.3±1.6), also achieved general visual improvements, from 0.65 to 0.52 logMAR in the first year. In contrast with the present results, it shows changes in BCVA and in the number of treatments on the basis of the neovascular process type, and conclude that CNV type 1 associates better vision and a higher number of injections at 4 years, and that visual gain in the rest of CNV is limited, probably due to the development of atrophy. However, as in the present study, all CNV types exhibited visual improvement in the first 12 months, which was greater in eyes with poorer baseline visions, and which began to deteriorate after 18 months of treatment.Matching the results of other studies, such as that published in 2007 by Jonas et al.<a class="elsevierStyleCrossRef" href="#bib0255">23</a> or in 2010 por Tao et al.<a class="elsevierStyleCrossRef" href="#bib0260">24</a>, which compared visual gain in different CNV types in the first year of treatment, the present study did not find statistical changes in BCVA according to CNV types. The data show that patients included in the CNV type 1I subgroup are less likely to gain ≥3 lines at the end of the treatment. These differences can be explained because CNV with poorer baseline vision are generally more advanced and, even though they initially respond positively to anti-VEGF, have a worse functional prognostic.<a class="elsevierStyleCrossRefs" href="#bib0205">13,14,25</a> In addition, the present study found baseline differences in ELM and EZ length, and this type of CNV exhibits the smallest baseline choroidal thickness, which could explain the greater difficulty to achieve higher visual gains.<a class="elsevierStyleCrossRefs" href="#bib0270">26,27</a>Recent studies have observed that macular choroidal thickness in patients with AMD is smaller than in healthy eyes.<a class="elsevierStyleCrossRef" href="#bib0270">26</a> In addition, choroidal thickness appears to diminish after treatment with aflibercept in eyes with AMD.<a class="elsevierStyleCrossRef" href="#bib0280">28</a> The results of the present study match those published by Koizumi et al.<a class="elsevierStyleCrossRef" href="#bib0280">28</a> and demonstrate choroidal thickness reductions in all eyes, not only at the subfoveal level but throughout the macula, which means that aflibercept could involve choroidal structures below the neovascular complex and reduce the exudative component.<a class="elsevierStyleCrossRef" href="#bib0280">28</a>As commented above, AMD could present different CNV phenotypes. A multimode diagnostic approach with FAG and OCT has promoted the classification in subtypes but it has also enabled the use of anatomical alterations as diagnostic and monitoring elements.<a class="elsevierStyleCrossRef" href="#bib0265">25</a> Despite being limited due to its retrospective design, a short follow-up period and the small number of patients included in each subgroup, the data of the present study indicate that treatment with aflibercept in TAE is efficient in all CNV subtypes. After a median of 7.72 injections and 6.89 visits in the course of one year, anatomical and functional improvement was obtained regardless of CNV type. Just like in clinical trials, TAE regime is effective in daily clinical practice. Visual gains obtained after the charge dose are maintained with said protocol, and at one year of treatment active exudation signs are virtually nonexistent.Conflict of interestsNo conflict of interests was declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres807361" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 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" => "xpalclavsec805258" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres807360" "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" => "xpalclavsec805257" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Subjects, material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Procedures and interventions" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Evaluated parameters" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-30" "fechaAceptado" => "2016-09-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec805258" "palabras" => array:6 [ 0 => "Aflibercept" 1 => "Treat and extend" 2 => "Retinal angiomatous proliferation" 3 => "Choroidal neovascularisation" 4 => "Spectral-domain optical coherence tomography" 5 => "Choroidal thickness" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec805257" "palabras" => array:6 [ 0 => "Aflibercept" 1 => "Tratar y extender" 2 => "Proliferación angiomatosa retiniana" 3 => "Neovascularización coroidea" 4 => "Tomografía de coherencia óptica de dominio espectral" 5 => "Grosor coroideo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo describe functional/morphological outcomes of treat-and-extend (TAE) with aflibercept in different subtypes of neovascularizations (CNV) secondary to exudative age-related macular degeneration (AMD). MethodsRetrospective study was conducted on 30 eyes of 30 patients treated with 2mg-aflibercept according to a TAE protocol. Examinations included best corrected visual acuity (BCVA), number of injections, and visits needed. A quantitative/qualitative analysis was also performed with fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT) at baseline, and at 3, 6, and 12 months. ResultsBCVA significantly improved from 0.61±0.26 logMAR to 0.38±0.34 logMAR. Among the total AMD patients, type 1 CNV was diagnosed in 11 eyes (36%), type 2 CNV in 7 eyes (23%), mixed CNV in 5 eyes (16%), and type 3 CNV or retinal angiomatous proliferation (RAP) in 7 eyes (23%). The final mean number of injections was 7.5±1.65, 8.71±0.76, 7.4±0.89, 7.2±0.7, and number of visits 6.6±2.17, 7.89±1.46, 5.8±1.7, and 7.14±1.57, respectively in type 1, type 2, mixed, and type 3 or RAP. There was no difference between the different subtypes of CNV (P>0.05). ConclusionsAflibercept in TAE is effective for all exudative-AMD subtypes. No significant differences in patient's visual gain, mean number of injections, or number of visits needed were found among the subtypes of CNV." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 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" => "ObjetivoDescribir los resultados funcionales/morfológicos del tratamiento con aflibercept en régimen del tipo tratar y extender (TE) en los diferentes tipos de neovascularizaciones (NVC) secundarias a la degeneración macular exudativa asociada a la edad (DMAE). MétodosEstudio retrospectivo en 30 ojos de 30 pacientes tratados con 2mg de aflibercept de acuerdo con un protocolo TE. Dentro de los parámetros analizados se incluyen la mejor agudeza visual corregida (MAVC) y el número de inyecciones y de visitas necesitado. Además, se incluyen los resultados de un análisis cuantitativo y cualitativo con angiofluoresceingrafía y tomografía de coherencia óptica de dominio espectral (SDOCT) al inicio y a los 3, 6 y 12 meses de seguimiento. ResultadosDe entre los pacientes con DMAE analizados, el componente de NVC de tipo 1 se encontró en 11 ojos (36%), el tipo 2 en 7 ojos (23%), el mixto en 5 ojos (16%) y el componente tipo 3 o proliferación angiomatosa retiniana (RAP), en 7 ojos (23%). La MAVC mejora significativamente de 0,61±0,26 logMAR a 0,38±0,34 logMAR. El número medio final de inyecciones fue de 7,5±1,65; 8,71±0,76; 7,4±0,89 y 7,2±0,7, y el de visitas de 6,6±2,17; 7,89±1,46; 5,8±1,7 y 7,14±1,57 respectivamente en membranas de tipo 1, de tipo 2, mixtas y de tipo 3 o RAP, que no difiere según el subtipo de NVC (p>0,05). ConclusionesAflibercept en pauta TE constituye un tratamiento eficaz en todos los tipos de NVC asociadas a DMAE. No se han observado diferencias significativas en ganancia visual, en el número medio de inyecciones ni en el número medio de visitas en función del subtipo de NVC." "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:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Castro-Navarro V, Cervera-Taulet E, Montero-Hernández J, Navarro-Palop C. Estrategia «Tratar y Extender» con aflibercept: efecto en diferentes tipos de neovascularización coroidea asociada a la edad. Arch Soc Esp Oftalmol. 2017;92:112–119." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1732 "Ancho" => 3246 "Tamanyo" => 335025 ] ] "descripcion" => array:1 [ "en" => "Changes in the main parameters of neovascularization subtypes. (A) functional changes and (B)–(F) anatomical changes between the different neovascularization types secondary to exudative age-related macular degeneration. Measurements were taken at baseline visit and at 3, 6 and 12 months. (a) Statistically significant changes were found between neovascularization type 1 and type 2 (a) and between neovascularization type 2 and type 3 or angiomatous retinal proliferation (b). PED: pigment epithelium detachment; CMT: central macular thickness; logMAR: logarithm of minimum angle of resolution; BCVA: best corrected visual acuity; ELM: external limiting membrane; CNV: neovascularization; RAP: retinal angiomatous proliferation; EZ: ellipsoid zone." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1448 "Ancho" => 1801 "Tamanyo" => 371897 ] ] "descripcion" => array:1 [ "en" => "Retinograph, fluorescein angiography and optical coherence tomography (OCT) of CNV type 3 or retinal angiomatous proliferation (RAP). (A)–(C) Color retinograph showing the clinical appearance of a stage 3 RAP. (B) Fluorescein angiography early stage and (C) late stage showing typical drusenoid staining and poorly defined intraretinal hyperfluorescence typical of RAP. (D)–(F) serial OCT explorations in (D) baseline visit; (E) at month 3 and (F) at month 12, showing complete resolution of intra-and subretinal fluid after Treat-and-Extend treatment with aflibercept. Note the changes in the serovascularized pigment epithelium detachment to the fibrovascularized type at the beginning and end of treatment." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Median±standard deviation, unless otherwise stated.PED: pigment epithelium detachment; CMT: central macular thickness; IRL: intraretinal liquid; logMAR: logarithm of minimum angle resolution; SRL: subretinal liquid; BCVA: best corrected visual acuity; ELM: external limiting membrane; CNV: choroidal neovascularization; RAP: retinal angiomatous proliferation; EZ: ellipsoid zone." "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="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">CNV type 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">CNV type 2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">CNV mixed \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">RAP \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">11 patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">5 patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76.18±8.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80.57±5.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81±3.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79.42±7.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex (male/female) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eye (right/left) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus (0/1)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypertension (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glaucoma (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anticoagulant or anti-aggregating treatment (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CNV localization (subfoveal/juxtafoveal/extrafoveal) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8/2/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/2/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/1/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/5/2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BCVA (logMAR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.50±0.219 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.718±0.298 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.674±0.342 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.514 ±0.195 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CMT (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">297.273±68.909 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">307.412±88.609 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">417±129.447 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">337±78.558 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Macular volume (cc) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.839±1.082 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.505 ±1.072 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.708±0.644 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.269±1.368 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SRL (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IRL (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">¾ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serovascularized PED (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrovascularized PED (0/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED maximum height (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">153.82±169.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">85.71±124.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">162.8±123.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">184.29±146.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED subfoveal height (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">102.18±128.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60.43±84.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52.2±116.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">125.29±154.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED nasal (μm) height 500μm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.82±123.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58.29±102.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.2±131.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64.43±82.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED temporal (μm) height 500μm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">113.27±146.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.86±54.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.2±114.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">110.29±163.44 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ELM length (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.698.73±188.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.680.29±193.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.474.8±222 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.828.57±179.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EZ LENGTH (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.587.64±357.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.434.71±73.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.363.6±168.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.644.57±370.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subfoveal choroidal thickness (μm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">214.36±36.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">191.57±24.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">219.2±21.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">220.86±21.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nasal (μm) choroidal thickness 500μm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">195.82±30.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">167±19.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">195.6±38.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">189.86±24.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temporal (μm) choroidal thickness 500μm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">220.45±42.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">196.29±34.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">221.2±37.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">235.71±19.49 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354805.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Where 0 indicates absence and 1 presence." ] ] ] "descripcion" => array:1 [ "en" => "Baseline demographic, functional and anatomical characteristics of CNV subtypes." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "PED: pigment epithelium detachment; IRL: intraretinal liquid; SRL: subretinal liquid; CNV: choroidal neovascularization; RAP: retinal angiomatous proliferation." "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="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 1</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 2</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV mixed</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">RAP</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">11 patients</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">5 patients</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SRL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IRL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serovascularized PED \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrovascularized PED \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354806.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Distribution per patient of morphological parameters in neovascularization subtypes." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "BCVA: best corrected visual acuity; CNV: choroidal neovascularization; RAP: retinal angiomatous proliferation." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameters \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">All subgroups n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 1 n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 2 n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV mixed n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">RAP n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Visit 2: follow-up at 3 months</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Number of eyes with BCVA improvements of:</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥1 line \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8532 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥2 lines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7294 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥3 lines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3774 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Changes between visit 2 and visit 3</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Number of eyes with BCVA improvements of:</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥1 line \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3301 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥2 lines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2(29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6234 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥3 lines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6178 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Visit 4: follow-up at 12 months</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Number of eyes with BCVA improvements of:</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥1 line \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9722 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥2 lines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7214 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥3 lines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1922 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354804.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "p indicates statistical significance between subgroups (Chi square test)." ] ] ] "descripcion" => array:1 [ "en" => "BCVA gains at 3, 6 and 12 months in CNV subtypes." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. 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Treat-and-extend approach with aflibercept: Effects on different subtypes of age-related choroidal neovascularisation

Estrategia «Tratar y Extender» con aflibercept: efecto en diferentes tipos de neovascularización coroidea asociada a la edad

V. Castro-Navarroa,b,

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veronicacastronavarro@gmail.com

Corresponding author.

, E. Cervera-Tauleta, J. Montero-Hernándeza, C. Navarro-Palopa

a Servicio de Oftalmología, Hospital General Universitario de Valencia, Valencia, Spain

b Escuela de Doctorado, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain

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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Retinograph&#44; fluorescein angiography and optical coherence tomography &#40;OCT&#41; of CNV type 3 or retinal angiomatous proliferation &#40;RAP&#41;&#46; &#40;A&#41;&#8211;&#40;C&#41; Color retinograph showing the clinical appearance of a stage 3 RAP&#46; &#40;B&#41; Fluorescein angiography early stage and &#40;C&#41; late stage showing typical drusenoid staining and poorly defined intraretinal hyperfluorescence typical of RAP&#46; &#40;D&#41;&#8211;&#40;F&#41; serial OCT explorations in &#40;D&#41; baseline visit&#59; &#40;E&#41; at month 3 and &#40;F&#41; at month 12&#44; showing complete resolution of intra-and subretinal fluid after Treat-and-Extend treatment with aflibercept&#46; Note the changes in the serovascularized pigment epithelium detachment to the fibrovascularized type at the beginning and end of treatment&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The era of multimodal image diagnostic has promoted the development of classifications for choroidal neovascularization &#40;CNV&#41; secondary to exudative age-related macular degeneration &#40;AMD&#41;&#46; Enhanced visualization also involves the discovery of anatomical characteristics that could influence visual results&#44; such as the presence of intra- or subretinal fluid&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> the integrity of the external limiting membrane &#40;ELM&#41; or the restoration of the ellipsoid zone &#40;EZ&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">2&#8211;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The VIEW 1 and 2<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a> pivotal studies with aflibercept&#44; a fusion protein derived from the combination of vascular endothelial growth factor &#40;VEGF&#41; receptor sequences 1 and 2&#44; demonstrated that 2<span class="elsevierStyleHsp" style=""></span>mg&#47;0&#46;05<span class="elsevierStyleHsp" style=""></span>mL of aflibercept every 8 weeks after a charge load of 3 monthly injections is not inferior to 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;0&#46;05<span class="elsevierStyleHsp" style=""></span>mL of ranibizumab every 4 weeks&#46; Even though the treat-and-extend &#40;TAE&#41; strategy has not been evaluated in the main clinical trials&#44; it constitutes a frequently utilized treatment protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">9</span></a> Randomized studies<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">10&#8211;12</span></a> as well as actual clinical practice<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#8211;15</span></a> demonstrated its capacity to produce visual acuity gains in treated patients up to 3 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#8211;15</span></a> Even though the CNV type 1s not a crucial parameter for selecting treatment protocol or a clear prognostic signal&#44; some of said studies have demonstrated increased benefits with this regime in type 1 neovascular membranes&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#44;14</span></a> Accordingly&#44; the authors believe it would be interesting to describe the visual and anatomic results with aflibercept in a TAE regime in different types of CNV expressing in AMD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects&#44; material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0015" class="elsevierStylePara elsevierViewall">A retrospective and observational study was designed for the anatomical and functional study in patients with CNV without previous treatment secondary to AMD&#46; Patients treated for said disease in the Macula Unit of the General University Hospital of Valencia between October 1&#44; 2014 and May 1&#44; 2015 were included consecutively in the study provided that they fulfilled the inclusion criteria&#44; lacked exclusion criteria and gave consent for the retrospective analysis of their data&#46; In compliance with Act 41&#47;2002 dated November 14&#44; the informed consent of all patients was obtained prior to beginning treatment with aflibercept and retrospective analyses&#46; The study was approved by the Ethics Committee of the Hospital&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Inclusion criteria comprised age &#8805;65&#44; best corrected visual acuity &#40;BCVA&#41; under 0&#46;1 logMAR&#44; the presence of untreated previous CNV secondary to AMD demonstrable with spectral domain optical coherence tomography &#40;SD-OCT&#41; and fluorescein angiography &#40;AGF&#41;&#44; a follow-up period of at least 12 months and the absence of other CNV causes such as polypoid vasculopathy or pathological myopia&#46; When polypoid vasculopathy was suspected&#44; indocyanine green angiography was performed&#44; discarding from the study the patients in whom this was confirmed&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">On the basis of the findings of FAG and SD-OCT and in accordance with the classification proposed by Freund<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> based on the histopathological findings of Gass&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a> 4 subtypes of neovascular complexes were obtained&#46; These are&#58; &#40;a&#41; type 1 CNV when the neovascular process was below the retina pigment epithelium &#40;RPE&#41;&#59; &#40;b&#41; type 2 CNV when the membrane had penetrated RPE and was above it&#44; in the subretinal space&#59; &#40;c&#41; mixed CNV when the neovascular tissue was above and below the RPE&#44; and &#40;d&#41; type 3 CNV or with retinal angiomatous proliferation &#40;RAP&#41; when neovascularization was intraretinal&#46; RAP stages were assigned in accordance with the classification established by Yanuzzi et al&#46; in 2001&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Procedures and interventions</span><p id="par0030" class="elsevierStylePara elsevierViewall">The patients received intravitreal treatment consisting of 2<span class="elsevierStyleHsp" style=""></span>mg aflibercept in 0&#46;05<span class="elsevierStyleHsp" style=""></span>mL in accordance with TAE treatment protocol&#44; carried out as follows&#58; after charge dose consisting of 3 monthly injections&#44; the patients were treated in all visits and evaluated as per the presence of exudative activity&#46; If active exudation was discarded&#44; the interval between visits was extended 2 weeks up to a maximum of 12 weeks&#46; On the contrary&#44; in the presence of some type of exudative activity&#44; the interval was shortened to the minimum acceptable period between visits&#44; i&#46;e&#46;&#44; 4 weeks&#46; Exudative activity was regarded as the presence&#47;appearance of subretinal liquid &#40;SRL&#41; or intraretinal liquid &#40;IRL&#41;&#44; increased central macular thickness &#40;CMT&#41; &#8805;100<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; and the appearance of new retinal hemorrhages or active leak in FAG&#46; The presence of persistent pigment epithelium detachment &#40;PED&#41; was not regarded as a re-treatment criterion&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Evaluated parameters</span><p id="par0035" class="elsevierStylePara elsevierViewall">AMD was diagnosed taking BCVA&#44; slit lamp examination&#44; SD-OCT and FAG &#40;50&#176; TopCon TRC-50IX Retinal Camera&#44; Topcon Medical Systems&#44; Inc&#46;&#44; Oakland&#44; USA&#44; and 5<span class="elsevierStyleHsp" style=""></span>mm of 10&#37; sodium fluorescein&#44; Fluoresce&#237;na &#211;culos 10&#37;&#59; Solution injectable&#44; Laboratorios SERB&#44; Brussels&#44; Belgium&#41;&#46; For the rest of the visits&#44; BCVA and SD-OCT examinations were performed&#46; Measures were recorded utilizing the data obtained at diagnostic &#40;baseline or at first visit data&#41;&#44; at month 3 when administering the last injection of the charge phase &#40;visit 2&#41; and at month 6 and 12 as of diagnostic &#40;visits 3 and 4&#44; respectively&#41;&#46; BCVA was examined with the Landolt C optotypes and expressed in the logarithm of minimum angle resolution &#40;logMAR&#41;&#46; The quantitative and qualitative analysis of SD-OCT images was carried out in SD-OCT B-scans and volume scans obtained under pupil dilatation with 3D-TopCon &#40;3D OCT-2000 SD-OCT&#44; Topcon Medical Systems&#44; Inc&#46;&#44; Oakland&#44; USA&#41;&#46; Equipment software confirmed the adequate positioning of the scanner and the obtained measures&#46; CMT and macular volume were generated automatically&#46; ELM and ZE discontinuity was evaluated according to the methods described by Oishi&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> in which a specialized technician who is not familiar with other clinical variables manually measures the length of said layers in a horizontal scanner passing through the fovea and including the region comprised between 1000 nasal microns and 1000 temporal microns from the foveal depression&#46; For the manual measurement of the choroidal thickness at the subfoveal level and in the 500 nasal and temporal microns&#44; the distance between the internal portion of the Bruch membrane and the chorioscleral interface was taken&#46; The presence or absence of SRL&#44; IRL or PED was analyzed&#46; PED height was taken as the maximum distance between the external RPE and the innermost part of the Bruch membrane&#46; When the PED was identified&#44; it was classified as serovascularized or fibrovascularized subtype&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The statistical analysis was carried out with the <span class="elsevierStyleItalic">R Statistical Software</span> &#40;version 3&#46;2&#46;2 Foundation for Statistical Computing&#44; 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starting from the baseline values of 1&#46;687&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>214&#46;87 and 1&#46;527&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>298&#46;13<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; respectively and rising to 1&#46;821&#46;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>104&#46;60 and 1&#46;766&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>127&#46;52<span class="elsevierStyleHsp" style=""></span>&#956;m&#46; At the end of the study&#44; choroidal thickness was found diminished in all locations&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As shown in the methods section&#44; CNV types were classified in subtypes&#58; &#40;a&#41; CNV type 1&#44; &#40;b&#41; CNV type 2&#44; &#40;c&#41; CNV mixed type and &#40;d&#41; CNV type 3 or RAP&#46; Quantitative and qualitative SD-OCT characteristics at baseline and month 3&#44; 6 and 12 are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Baseline differences were identified after a Kruskal&#8211;Wallis analysis&#46; CNV type 2 exhibited the lowest BCVA &#40;0&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;18 logMAR&#59; KW<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;65&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00217&#41;&#46; The final mean number of injections &#40;7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;65 in CNV subgroup type 1&#59; 8&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;76 in CNV type 2&#59; 7&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;89 in mixed CNV and 7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7 in RAP&#41; and of visits &#40;6&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;17&#59; 7&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;46&#59; 5&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7 and 7&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;57&#44; respectively&#41; was not different between each neovascular complex type&#46; In what concerns functional parameters&#44; visual acuity gain did not vary between the 4 subgroups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">When analyzing anatomical changes in SD-OCT the following characteristics were obtained &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58; CNV type 1 exhibited the lowest baseline CMT and the PED rate of 72&#37;&#44; which diminished with treatment&#46; As regards CNV type 2&#44; these associated mean CMT and MV values&#44; while IRL and SRL were found to be 57 and 85&#37;&#44; with partial resolution after aflibercept&#46; A noteworthy finding in this CNV type 1s lower choroidal thickness than in the other subgroups&#44; which remained stable throughout the study&#46; Due to the presence of the neovascular component above as well as below the RPE&#44; the mixed type of CNV exhibited anatomic alterations typical of CNV types 1 and 2&#46; Said subtype exhibited the largest CMT &#40;417<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>129&#46;45<span class="elsevierStyleHsp" style=""></span>&#956;m&#41; and MV &#40;8&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;64<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span>&#41; at diagnostic with IRL&#44; SRL and PED in 80&#44; 100 and 80&#37; of cases&#44; respectively&#46; Even though the disruption of ELM and EZ in this CNV subtype was greater than in the rest&#44; length increases were observed with treatment&#46; Type 3 or RAP lesions&#44; in which neovascularization begins inside the retina&#44; showed intermediate CMT and MV values &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; External retina layers exhibited lower baseline alteration &#40;1&#46;828&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>179&#46;25 and 1&#46;644&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>370&#46;93<span class="elsevierStyleHsp" style=""></span>&#956;m length in ELM and EZ&#44; respectively&#41; and their integrity increased with treatment&#46; As occurs in CNV type 1 and mixed&#44; a progressive reduction in choroidal thickness was observed&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The results obtained in the present study demonstrate that TAE treatment with aflibercept during 12 months is an effective tool in AMD&#46; Said results show that visual gain in these patients does not initially depend on the CNV subtype&#46; The TAE protocol is a proactive individualized treatment which at present is frequently applied&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">9&#44;13</span></a> In order to obtain a fluid-free macula&#44; TAE enables the application of an individualized treatment frequency&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">9&#44;19</span></a> Randomized clinical trials with ranibizumab and bevacizumab have demonstrated their efficiency with visual gains similar to monthly regimes&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">10&#8211;12</span></a> Accordingly&#44; ranibizumab groups with a mean number of injections of 8 to 10&#46;1 in the first year and starting from mean baseline values of 60&#46;5&#8211;62 ETDRS letters &#40;approximately 0&#46;5 logMAR&#41;&#44; visual acuity gains of &#43;8&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;5 &#40;approximately 0&#46;3 logMAR&#41; were obtained&#46; The present study&#44; with a median of 7&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;25 injections&#44; shows a significant BCVA improvement&#44; from 0&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;26 to 0&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;34 logMAR&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">As the TAE strategy enables individual control&#44; it has been proposed as the first choice in CNV type 1 or RAP&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">20&#44;21</span></a> In the present study the patients were grouped on the basis of CNV type by means of a multimodal analysis&#46; Despite the limitation of the small number of patients&#44; study data demonstrate that said therapeutic regime is effective for all groups at 12 months&#46; After a similar mean number of injections and visits&#44; BCVA in the last visit improved up to 0&#46;36&#59; 0&#46;52&#59; 0&#46;3 and 0&#46;3 logMAR in CNV type 1&#44; type 2&#44; mixed and type 3 or RAP&#44; respectively&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Even though the present study is based on usual clinical practice&#44; it includes baseline characteristics and visual gains similar to those of clinical trials and matching other retrospective studies&#46; Similar or worse baseline visual values exhibited visual gains similar to those of the present study&#44; in the area of 10 EDTRS letters&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#44;15</span></a> However&#44; when starting from a higher visual acuity&#44; it tends to remain stable&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> Mrejen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a> assessed TAE in different lesions&#46; Said study&#44; with a mean number of annual injections similar to those of the present study &#40;8&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&#41;&#44; also achieved general visual improvements&#44; from 0&#46;65 to 0&#46;52 logMAR in the first year&#46; In contrast with the present results&#44; it shows changes in BCVA and in the number of treatments on the basis of the neovascular process type&#44; and conclude that CNV type 1 associates better vision and a higher number of injections at 4 years&#44; and that visual gain in the rest of CNV is limited&#44; probably due to the development of atrophy&#46; However&#44; as in the present study&#44; all CNV types exhibited visual improvement in the first 12 months&#44; which was greater in eyes with poorer baseline visions&#44; and which began to deteriorate after 18 months of treatment&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Matching the results of other studies&#44; such as that published in 2007 by Jonas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> or in 2010 por Tao et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span> which compared visual gain in different CNV types in the first year of treatment&#44; the present study did not find statistical changes in BCVA according to CNV types&#46; The data show that patients included in the CNV type 1I subgroup are less likely to gain &#8805;3 lines at the end of the treatment&#46; These differences can be explained because CNV with poorer baseline vision are generally more advanced and&#44; even though they initially respond positively to anti-VEGF&#44; have a worse functional prognostic&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13&#44;14&#44;25</span></a> In addition&#44; the present study found baseline differences in ELM and EZ length&#44; and this type of CNV exhibits the smallest baseline choroidal thickness&#44; which could explain the greater difficulty to achieve higher visual gains&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Recent studies have observed that macular choroidal thickness in patients with AMD is smaller than in healthy eyes&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">26</span></a> In addition&#44; choroidal thickness appears to diminish after treatment with aflibercept in eyes with AMD&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a> The results of the present study match those published by Koizumi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a> and demonstrate choroidal thickness reductions in all eyes&#44; not only at the subfoveal level but throughout the macula&#44; which means that aflibercept could involve choroidal structures below the neovascular complex and reduce the exudative component&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">As commented above&#44; AMD could present different CNV phenotypes&#46; A multimode diagnostic approach with FAG and OCT has promoted the classification in subtypes but it has also enabled the use of anatomical alterations as diagnostic and monitoring elements&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a> Despite being limited due to its retrospective design&#44; a short follow-up period and the small number of patients included in each subgroup&#44; the data of the present study indicate that treatment with aflibercept in TAE is efficient in all CNV subtypes&#46; After a median of 7&#46;72 injections and 6&#46;89 visits in the course of one year&#44; anatomical and functional improvement was obtained regardless of CNV type&#46; Just like in clinical trials&#44; TAE regime is effective in daily clinical practice&#46; Visual gains obtained after the charge dose are maintained with said protocol&#44; and at one year of treatment active exudation signs are virtually nonexistent&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interests</span><p id="par0100" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors&#46;</p></span></span>"
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            1 => "Treat and extend"
            2 => "Retinal angiomatous proliferation"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe functional&#47;morphological outcomes of treat-and-extend &#40;TAE&#41; with aflibercept in different subtypes of neovascularizations &#40;CNV&#41; secondary to exudative age-related macular degeneration &#40;AMD&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective study was conducted on 30 eyes of 30 patients treated with 2<span class="elsevierStyleHsp" style=""></span>mg-aflibercept according to a TAE protocol&#46; Examinations included best corrected visual acuity &#40;BCVA&#41;&#44; number of injections&#44; and visits needed&#46; A quantitative&#47;qualitative analysis was also performed with fluorescein angiography and spectral-domain optical coherence tomography &#40;SD-OCT&#41; at baseline&#44; and at 3&#44; 6&#44; and 12 months&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">BCVA significantly improved from 0&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;26 logMAR to 0&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;34 logMAR&#46; Among the total AMD patients&#44; type 1 CNV was diagnosed in 11 eyes &#40;36&#37;&#41;&#44; type 2 CNV in 7 eyes &#40;23&#37;&#41;&#44; mixed CNV in 5 eyes &#40;16&#37;&#41;&#44; and type 3 CNV or retinal angiomatous proliferation &#40;RAP&#41; in 7 eyes &#40;23&#37;&#41;&#46; The final mean number of injections was 7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;65&#44; 8&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;76&#44; 7&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;89&#44; 7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#44; and number of visits 6&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;17&#44; 7&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;46&#44; 5&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&#44; and 7&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;57&#44; respectively in type 1&#44; type 2&#44; mixed&#44; and type 3 or RAP&#46; There was no difference between the different subtypes of CNV &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Aflibercept in TAE is effective for all exudative-AMD subtypes&#46; No significant differences in patient&#39;s visual gain&#44; mean number of injections&#44; or number of visits needed were found among the subtypes of CNV&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir los resultados funcionales&#47;morfol&#243;gicos del tratamiento con aflibercept en r&#233;gimen del tipo tratar y extender &#40;TE&#41; en los diferentes tipos de neovascularizaciones &#40;NVC&#41; secundarias a la degeneraci&#243;n macular exudativa asociada a la edad &#40;DMAE&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo en 30 ojos de 30 pacientes tratados con 2<span class="elsevierStyleHsp" style=""></span>mg de aflibercept de acuerdo con un protocolo TE&#46; Dentro de los par&#225;metros analizados se incluyen la mejor agudeza visual corregida &#40;MAVC&#41; y el n&#250;mero de inyecciones y de visitas necesitado&#46; Adem&#225;s&#44; se incluyen los resultados de un an&#225;lisis cuantitativo y cualitativo con angiofluoresceingraf&#237;a y tomograf&#237;a de coherencia &#243;ptica de dominio espectral &#40;SDOCT&#41; al inicio y a los 3&#44; 6 y 12 meses de seguimiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De entre los pacientes con DMAE analizados&#44; el componente de NVC de tipo 1 se encontr&#243; en 11 ojos &#40;36&#37;&#41;&#44; el tipo 2 en 7 ojos &#40;23&#37;&#41;&#44; el mixto en 5 ojos &#40;16&#37;&#41; y el componente tipo 3 o proliferaci&#243;n angiomatosa retiniana &#40;RAP&#41;&#44; en 7 ojos &#40;23&#37;&#41;&#46; La MAVC mejora significativamente de 0&#44;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;26 logMAR a 0&#44;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;34 logMAR&#46; El n&#250;mero medio final de inyecciones fue de 7&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;65&#59; 8&#44;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;76&#59; 7&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;89 y 7&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;7&#44; y el de visitas de 6&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;17&#59; 7&#44;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;46&#59; 5&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 y 7&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;57 respectivamente en membranas de tipo 1&#44; de tipo 2&#44; mixtas y de tipo 3 o RAP&#44; que no difiere seg&#250;n el subtipo de NVC &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Aflibercept en pauta TE constituye un tratamiento eficaz en todos los tipos de NVC asociadas a DMAE&#46; No se han observado diferencias significativas en ganancia visual&#44; en el n&#250;mero medio de inyecciones ni en el n&#250;mero medio de visitas en funci&#243;n del subtipo de NVC&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Castro-Navarro V&#44; Cervera-Taulet E&#44; Montero-Hern&#225;ndez J&#44; Navarro-Palop C&#46; Estrategia &#171;Tratar y Extender&#187; con aflibercept&#58; efecto en diferentes tipos de neovascularizaci&#243;n coroidea asociada a la edad&#46; Arch Soc Esp Oftalmol&#46; 2017&#59;92&#58;112&#8211;119&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1732
            "Ancho" => 3246
            "Tamanyo" => 335025
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Changes in the main parameters of neovascularization subtypes&#46; &#40;A&#41; functional changes and &#40;B&#41;&#8211;&#40;F&#41; anatomical changes between the different neovascularization types secondary to exudative age-related macular degeneration&#46; Measurements were taken at baseline visit and at 3&#44; 6 and 12 months&#46; &#40;a&#41; Statistically significant changes were found between neovascularization type 1 and type 2 &#40;a&#41; and between neovascularization type 2 and type 3 or angiomatous retinal proliferation &#40;b&#41;&#46; PED&#58; pigment epithelium detachment&#59; CMT&#58; central macular thickness&#59; logMAR&#58; logarithm of minimum angle of resolution&#59; BCVA&#58; best corrected visual acuity&#59; ELM&#58; external limiting membrane&#59; CNV&#58; neovascularization&#59; RAP&#58; retinal angiomatous proliferation&#59; EZ&#58; ellipsoid zone&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1448
            "Ancho" => 1801
            "Tamanyo" => 371897
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Retinograph&#44; fluorescein angiography and optical coherence tomography &#40;OCT&#41; of CNV type 3 or retinal angiomatous proliferation &#40;RAP&#41;&#46; &#40;A&#41;&#8211;&#40;C&#41; Color retinograph showing the clinical appearance of a stage 3 RAP&#46; &#40;B&#41; Fluorescein angiography early stage and &#40;C&#41; late stage showing typical drusenoid staining and poorly defined intraretinal hyperfluorescence typical of RAP&#46; &#40;D&#41;&#8211;&#40;F&#41; serial OCT explorations in &#40;D&#41; baseline visit&#59; &#40;E&#41; at month 3 and &#40;F&#41; at month 12&#44; showing complete resolution of intra-and subretinal fluid after Treat-and-Extend treatment with aflibercept&#46; Note the changes in the serovascularized pigment epithelium detachment to the fibrovascularized type at the beginning and end of treatment&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Median<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#44; unless otherwise stated&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">PED&#58; pigment epithelium detachment&#59; CMT&#58; central macular thickness&#59; IRL&#58; intraretinal liquid&#59; logMAR&#58; logarithm of minimum angle resolution&#59; SRL&#58; subretinal liquid&#59; BCVA&#58; best corrected visual acuity&#59; ELM&#58; external limiting membrane&#59; CNV&#58; choroidal neovascularization&#59; RAP&#58; retinal angiomatous proliferation&#59; EZ&#58; ellipsoid zone&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col">CNV type 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col">CNV type 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col">CNV mixed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col">RAP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">11 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">5 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex &#40;male&#47;female&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eye &#40;right&#47;left&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus &#40;0&#47;1&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypertension &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glaucoma &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anticoagulant or anti-aggregating treatment &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CNV localization &#40;subfoveal&#47;juxtafoveal&#47;extrafoveal&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#47;2&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;2&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;1&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#47;5&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BCVA &#40;logMAR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;219&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;718<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;298&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;674<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;342&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;514 &#177;0&#46;195&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CMT &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">297&#46;273<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&#46;909&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">307&#46;412<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>88&#46;609&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">417<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>129&#46;447&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">337<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>78&#46;558&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Macular volume &#40;cc&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;839<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;082&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;505 &#177;1&#46;072&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;708<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;644&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;269<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SRL &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IRL &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#190;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serovascularized PED &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrovascularized PED &#40;0&#47;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED maximum height &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">153&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>169&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>124&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">162&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>123&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">184&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>146&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED subfoveal height &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">102&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>128&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>84&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>116&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">125&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>154&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED nasal &#40;&#956;m&#41; height 500<span class="elsevierStyleHsp" style=""></span>&#956;m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>123&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>102&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>131&#46;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>82&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PED temporal &#40;&#956;m&#41; height 500<span class="elsevierStyleHsp" style=""></span>&#956;m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>146&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>54&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>114&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">110&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>163&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ELM length &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;698&#46;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>188&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;680&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>193&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;474&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;828&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>179&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EZ LENGTH &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;587&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>357&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;434&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>73&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;363&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>168&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;644&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>370&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subfoveal choroidal thickness &#40;&#956;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">214&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">191&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">219&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">220&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nasal &#40;&#956;m&#41; choroidal thickness 500<span class="elsevierStyleHsp" style=""></span>&#956;m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">195&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">167<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">195&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>38&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">189&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temporal &#40;&#956;m&#41; choroidal thickness 500<span class="elsevierStyleHsp" style=""></span>&#956;m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">220&#46;45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">196&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>34&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">221&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">235&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">PED&#58; pigment epithelium detachment&#59; IRL&#58; intraretinal liquid&#59; SRL&#58; subretinal liquid&#59; CNV&#58; choroidal neovascularization&#59; RAP&#58; retinal angiomatous proliferation&#46;</p>"
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                  <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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 1</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 2</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV mixed</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">RAP</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">11 patients</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">5 patients</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7 patients</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SRL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IRL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serovascularized PED&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrovascularized PED&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">BCVA&#58; best corrected visual acuity&#59; CNV&#58; choroidal neovascularization&#59; RAP&#58; retinal angiomatous proliferation&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">All subgroups n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 1 n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV type 2 n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CNV mixed n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">RAP n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleBold">Visit 2&#58; follow-up at 3 months</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Number of eyes with BCVA improvements of&#58;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;1 line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;59&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8532&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;2 lines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;3 lines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3774&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleBold">Changes between visit 2 and visit 3</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Number of eyes with BCVA improvements of&#58;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;1 line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;2 lines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;3 lines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6178&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleBold">Visit 4&#58; follow-up at 12 months</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Number of eyes with BCVA improvements of&#58;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;1 line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9722&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;2 lines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7214&nbsp;\t\t\t\t\t\t\n
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