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 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; Vienna&#44; Austria&#41;&#46; The descriptive analysis of data included median&#44; standard deviation and percentages when necessary&#46; The variables were studied utilizing the <span class="elsevierStyleItalic">T</span> for Student test for parametric variables&#44; the Wilcoxon and Kruskal&#8211;Wallis test for nonparametric variables and the Chi square test&#46; Statistical significance was defined when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">The study included 30 eyes of 30 patients&#44; with a median age of 78&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;9 years&#46; Type 1 neovascular component was found in 11 eyes &#40;36&#37;&#41;&#44; type 2 in 7 eyes &#40;23&#37;&#41;&#44; mixed in 5 eyes &#40;16&#37;&#41; and type 3 or RAP component in 7 eyes &#40;23&#37;&#41;&#46; In the group of RAP subtype patients one eye was identified with stage 2 without PED&#44; 3 eyes with stage 2 with PED and 3 eyes with stage 3 of the disease&#46; The demographic and baseline characteristics of patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">After the charge dose a significant change in BCVA was identified&#44; increasing from 0&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;26 logMAR to 0&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;32 logMAR&#46; At month 12&#44; after a median of 6&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;85 visits and 7&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;25 injections&#44; final BCVA was 0&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;34 logMAR&#46; Similarly&#44; at the end of the study a significant reduction of CMT and MV was observed&#46; Morphological parameter analysis showed that&#44; after the charge dose&#44; SRL at baseline visit &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41;&#44; IRL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#41; and serovascularized PED &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; diminished significantly&#44; demonstrating stable results at month 12&#46; ELM and ZE length increased significantly &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;011 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00006&#41;&#44; 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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            5 => "Choroidal thickness"
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        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec805257"
          "palabras" => array:6 [
            0 => "Aflibercept"
            1 => "Tratar y extender"
            2 => "Proliferaci&#243;n angiomatosa retiniana"
            3 => "Neovascularizaci&#243;n coroidea"
            4 => "Tomograf&#237;a de coherencia &#243;ptica de dominio espectral"
            5 => "Grosor coroideo"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "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>"
        "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" => "<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
          ]
        ]
        "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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                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&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
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