Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration | Archivos de la Sociedad Española de Oftalmología (English Edition)

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In face examination identifying three different layers of the choroids: (a) choriocapillary; (b) median vessels layer; (c) large vessels layer. B-scans artificially “flatten out” at the selected level (green line). The yellow line shows the level of the choroids shown in the upper scan." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Ruiz-Medrano, I. Flores-Moreno, R. Gutierrez-Bonet, J. Chhablani, J.M. Ruiz-Moreno" "autores" => array:5 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Ruiz-Medrano" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Flores-Moreno" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Gutierrez-Bonet" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Chhablani" ] 4 => array:2 [ "nombre" => "J.M." 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(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." ] ] ] "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." "apellidos" => "Cervera-Taulet" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Montero-Hernández" ] 3 => array:2 [ "nombre" => "C." 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Gallego-Pinazo, R. Dolz-Marco, M. Andreu-Fenoll, J. Farrés, L. Monclús" "autores" => array:5 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Gallego-Pinazo" "email" => array:1 [ 0 => "robertogallego@comv.es" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R." "apellidos" => "Dolz-Marco" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Andreu-Fenoll" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "J." 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"apellidos" => "Monclús" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Mácula, Servicio de Oftalmología, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "RETICS RD160008 Enfermedades oculares, Prevención, detección precoz, tratamiento y rehabilitación de las enfermedades oculares, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto de Investigaciones Sanitarias La Fe, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Bayer Hispania, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Impacto funcional del tratamiento con ranibizumab bajo una estrategia reactiva en pacientes con degeneración macular asociada a la edad exudativa neovascular" ] ] "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" => 1464 "Tamanyo" => 161131 ] ] "descripcion" => array:1 [ "en" => "Changes in VA (%) during the entire follow-up period. Changes in VA during the entire follow-up period (from 3 to 18 months), in percentages (%)." ] ] ] "textoCompleto" => "IntroductionAge-related macular degeneration (AMD) is the most frequent cause of legal blindness in patients over 50 in the Western world.<a class="elsevierStyleCrossRef" href="#bib0090">1</a> The global prevalence is estimated at 1% in subjects between 65 and 74 years of age, 5% between 75 and 84 and 13% in subjects over 85.<a class="elsevierStyleCrossRef" href="#bib0095">2</a> The first prevalence study in Spain was carried out in a population over 65, finding a prevalence of 3.4%.<a class="elsevierStyleCrossRef" href="#bib0100">3</a> The incidence of AMD increases exponentially with age and accordingly a significant increase is estimated in the next few years due to progressive population aging. For this reason, early and adequate AMD diagnostic will become a social and health challenge that must be taken up by retinologists and ophthalmologists.Intravitreal vascular endothelial growth factor (VEGF) inhibitors injections are the treatment of choice for visual compromise caused by neovascular AMD.<a class="elsevierStyleCrossRefs" href="#bib0105">4,5</a> Pivotal phase 3 studies with ranibizumab administered in monthly injections during 2 years (ANCHOR<a class="elsevierStyleCrossRef" href="#bib0105">4</a> and MARINA<a class="elsevierStyleCrossRef" href="#bib0110">5</a>) demonstrated significant visual acuity (VA) improvements. However, this long follow-up with monthly treatments involves a difficult to cover cost in daily clinical practice and could involve increased risk at the ocular<a class="elsevierStyleCrossRef" href="#bib0110">5</a> and systemic level.<a class="elsevierStyleCrossRef" href="#bib0115">6</a> In response to these problems, alternative dosage strategies have been considered for said treatments to produce the same efficacy but with a lower number of visits and injections. The first was the injection on-demand regime or pro re nata (PRN)<a class="elsevierStyleCrossRefs" href="#bib0120">7,8</a> according to which, after an initial dosage during the first 3 months, strictly monthly visits are prescribed to administer retreatments on the basis of VA or changes in optical coherence tomography (OCT). However, this strategy does not diminish the number of visits as patients must undergo an examination every 4 weeks to detect relapses at an early stage, and accordingly the burden on health services remains high. The Comparison made by the Age-Related macular Degeneration Treatment Trials (CATT) study demonstrated that the PRN strategy is inferior in efficacy to monthly treatment and that, even after one year of monthly treatment, efficacy diminishes when changing the regimen to reactive treatment in the second year.<a class="elsevierStyleCrossRef" href="#bib0120">7</a>The Inhibit VEGF in Age-Related Choroidal Neovascularisation (IVAN) study analyzed a different retreatment strategy consisting in injections during 3 consecutive months after a relapse. Even so, diminished VA could not be recovered after the reactivation and the VA results with this PRN regimen did not demonstrate to be equal to those obtained with a fixed treatment regimen.<a class="elsevierStyleCrossRef" href="#bib0130">9</a>The irreversible deterioration of vision, which is apparently intrinsic to the PRN treatment regimen, entails the impossibility of strict monthly follow-ups in daily clinical practice. Accordingly, the effectiveness of the on-demand prescription is even lower despite experiencing initial VA improvements because these cannot be maintained due to longer periods between visits and to diminished treatment dosages throughout the follow-up period.<a class="elsevierStyleCrossRef" href="#bib0135">10</a>A further follow-up strategy proposes that treatment should not be made when recurrences are detected; instead, the treatment should be administrated previously. This is known as “treat and extend” treatment.<a class="elsevierStyleCrossRef" href="#bib0140">11</a>Some authors have observed that eventual visual losses associated to the reactivation of the neovascular lesion during a PRN follow-up do not recover completely even when treatment is administrated, and indicate 53–67% of restoration of vision in the subgroup of patients who lost over 5 letters. Accordingly, treatment should be proactive in order to avoid or stretch out in time relapses of existing lesions.<a class="elsevierStyleCrossRefs" href="#bib0140">11,12</a> It can be seen that the strategy for treating and following up patients with neovascular AMD remains an open debate in a search to achieve more efficient management of antiangiogenic medicaments in daily practice, which is generally burdened with excessive workloads.In-depth knowledge about the evolution of the disease and its response to on-demand or reactive treatment (the most widely utilized at present) is essential to optimize the approach to this disease. The objective of the present study is to assess the functional recovery percentage after visual loss in a PRN follow-up with ranibizumab in patients with neovascular AMD followed up in a single hospital specialized in this disease by a single retina specialist.MethodsAn observational, retrospective and single center study (EPA-RE) in patients fulfilling the following criteria: (1) new neovascular AMD diagnostic and at least 18 months of follow-up in the hospital; (2) treatment with ranibizumab with on-demand regimen with frequent checkups and retreatments in the presence of any intra-or subretinal fluid in OCT and VA loss of at least one decimal fraction; (3) patients with medical records and information since AMD was diagnosed at the hospital. Clinic record reviews were carried out in the Macula Unit of the University and Polytechnic Hospital La Fe of Valencia, and included the records of patients in consecutive order from diagnostic date to avoid selection bias. The retrospective observation period was 18 months. The eye of the study was the one which had at least 18 months treatment with ranibizumab and, in case of bilateral involvement, the first diagnosed eye or the one with better VA if both had been diagnosed at the same time.The study was approved by the Medicaments Agency of Spain and the Ethical Committee of the University Hospital La Fe of Valencia.Sociodemographic data were collected (age, sex, race, color of eyes and tobacco smoking) as well as clinical data (diagnostic date, affected eye, lesion size, retinal and foveal thickness) of the patients included in the study through the clinic records or other source documents.The analysis of the main objective was focused on estimating the VA (recovery percentage assessed by means of the Snellen test) after retreatments. Two different methods were applied in order to calculate VA after retreatments (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>):<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Method 1: VA recovery percentage=(VA recovered after treatment/VA lost prior to treatment)×100, where:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-VA recovered after treatment was defined as the difference between the best VA achieved during the 3 months after retreatment and that recorded at the visit that gave rise to the retreatment.</li><li class="elsevierStyleListItem" id="lsti0010">-VA lost prior to treatment was defined as the difference between the VA achieved in the previous visit that gave rise to the retreatment and the VA recorded at the retreatment visit.</li></ul>Method 2: VA recovery percentage: (VA recovered after treatment/VA lost prior to treatment)×100, where:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">-VA recovered after treatment was defined as the difference between the best VA achieved during the 3 months after retreatment and that recorded at the visit that gave rise to the retreatment.</li><li class="elsevierStyleListItem" id="lsti0020">-VA lost prior to retreatment was defined as the difference between the best VA achieved during follow-up between the previous dose and that of retreatment, and VA achieved at the retreatment visit.</li></ul>Statistical analysisThe clinic and sociodemographic data were submitted to a descriptive analysis, analyzing the evolution of clinical variables (retinal thickness, clinic results, VA and concomitant ophthalmological diseases) by means of the Student t-test. All the continuous variables were analyzed as mean, standard deviation (SD), maximum and minimum recorded values, median and quartiles. A significance value of 0.05 was taken into account in all cases. The statistical analysis was carried out with the SAS application version 9.2 (SAS Institute Inc., Cary, NC, USA) in Windows™ (SAS Institute Inc. 2008. SAS/STAT®9.2 User's Guide. Cary, NC: SAS Institute Inc. Copyright © 2008. SAS Institute Inc., Cary, NC, USA).ResultsOverall, the study included 150 patients of which 128 were assessable while 22 patients did not have recorded retreatments due to loss of VA during the follow-up period.The mean follow-up of patients was 18.9 (SD 2.3) months. The sample comprised 60.2% of females and 38.2% of males, with a mean age of 76.0 (SD 8.8) years. Virtually all patients (98.4%) exhibited at diagnostic unilateral compromise caused by neovascular AMD. In 55.6% of cases the studied eye was the left (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Overall, 62.5% of patients reported sudden and progressive VA reduction at diagnostic. Only 50 of the 128 patients included in the study had data recorded in their clinical records indicating the time elapsed between the first symptoms and the AMD diagnostic, with a mean age of (SD 57.4) days.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The mean number of visits was 12.5 (SD 3.1), with an interval of 50–20 visits. Regarding the location of the neovascular lesion, the most frequent was subfoveal (63.3%), followed by juxtapapillar (30.5%). The number of visits was significantly higher for patients with subfoveal lesions (48.4 [SD 39.5] days) against those with juxtapapillar lesions (41.9 [SD 18.5] days; p=0.043). Approximately 80% of patients exhibited lesions between 1 and 2 or over 2 optic discs. In what concerns size changes and comparison with the baseline, statistically significant differences were observed after 18 months (p=0.0302). No statistically significant differences were observed in the number or frequency of visits or lesion location at diagnostic.In what concerns the morphological classic patient of neovascular lesions based on OCT, 54.7% were type I lesions (hidden), 19.5% were type III (retinal angiomatous proliferation), 17.2% were type II (classic) and 6.8% were identified as polypoid choroidal vasculopathy. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the clinic results observed most frequently at diagnostic. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes the evolution of macular and retinal thickness at each follow-up period in comparison with baseline. Statistically significant differences were observed in comparison with the baseline period (p<0.0001) for both the variables and these remained similar throughout the follow-up period.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The mean of 10.9 days and a median of 4 days elapsed between prescription and the first administration of ranibizumab, and in 68.0% of cases the first treatment was administered a few days after the baseline period. During the follow-up period, patients received a mean (min., max.) of 6.0 (1, 14) and a median of 5 treatments. The most frequent reason for receiving treatment was the reappearance/persistence of subretinal fluid (71.9%), followed by initial treatment (57.8%) and reappearance/persistence of intraretinal fluid (57.0%). In all 128 included patients, the mean (SD) number of visits was 12.5 (3.1) and the median of 12.5.General visual results<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> compares changes in VA in terms of patient percentages during the follow-up period where, in the baseline situation, the mean VA was 43.79 (SD 22.6) letters, and during the follow-up periods it improved with a mean VA after eighteen months of 53.2 (SD 22.4).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Percentage of recovered visual acuity after a loss of five lettersThe results for loss, gain and percentage of VA recovery in letters were analyzed with the two methods described above, as shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> compares both methods and the percentage of recovered VA after retreatment with both methods:<elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>Method 1: 108 retreatments due to recurring exudative signs associated to visual deterioration of five or more letters that had all the information to calculate the VA recovery percentage. Said 108 retreatments exhibited a mean VA loss of 10.5 (SD 15.7) letters before retreatment. However, the mean gain observed after retreatment was 7.59 (SD 12.94) letters, corresponding to the mean VA recovery percentage of 70.03% (SD 114.37) when compared to VA before retreatment. In this case, forty-eight percent of retreatments exhibited a recovery percentage below 75%.Method 2: 162 retreatments were registered due to recurring exudative signs associated to visual impairment of 5 or more letters having information for calculating the VA recovery percentage. Said 162 retreatments exhibited a mean loss of 15.1 (SD 13.2) letters prior to retreatment and the mean gain after retreatment of 7.96 (SD 12.88) letters, corresponding to a mean VA recovery of 43.5% when comparing between the best reported VA and the last initial dose or the previous retreatment. Overall, 54.3% of retreatments exhibited a VA recovery percentage below 75%.DiscussionEven in the absence of any scientific evidence demonstrating that PRN regimes are equivalent to fixed regimes, the need to reduce the amount of visits influence the adoption of this strategy in clinical practice. It is necessary to delve deeper in the knowledge of the disease and in the respondents of the “reactive or on-demand PRN” with anti-VEGF agents in order to design improved therapeutic approaches for AML.Some studies have demonstrated that ranibizumab is effective in a fixed monthly treatment regimen with a VA recovery of 7.2 and 11.3 letters at 12 months.<a class="elsevierStyleCrossRefs" href="#bib0105">4,5</a> The problem associated to this high efficiency strategy is that it involves a high number of visits and injections which are difficult to apply in clinical practice. In addition, it could be considered that some patients are overtreated with a fixed monthly treatment regimen.As an alternative, some studies reported modification of said regimen utilizing the so-called on-demand strategy or PRN which carries out retreatments only on the basis of OCT parameters or diminished VA. This strategy is more individualized but its disadvantage is that it requires strict monthly follow-up visits to minimize vision impairment with each reactivation of the disease. Accordingly, even though the number of injections can be diminished in some cases, it is necessary to maintain the number of follow-up visits, making this regimen a highly expensive and difficult to apply approach in hospitals with high workloads.<a class="elsevierStyleCrossRef" href="#bib0150">13</a> In addition, the results provided in the IVAN,<a class="elsevierStyleCrossRef" href="#bib0130">9</a> CATT<a class="elsevierStyleCrossRef" href="#bib0120">7</a> and HARBOR<a class="elsevierStyleCrossRef" href="#bib0125">8</a> studies demonstrated that the functional and anatomical efficacy of PRN regimes did not reach the efficacy achieved by the monthly administration regimes.The appearance of the treat and extend regimen provides an alternative to treat patients with neovascular AMD without waiting for a relapse, progressively increasing intervals between visits.<a class="elsevierStyleCrossRefs" href="#bib0140">11,14</a> This enables a workload reduction and avoids patient overtreatment. Conceptually, the functional results of this strategy should be better than those provided by the PRN regimes, as the treatment anticipates relapses and endeavors to avoid them. The results of the LUCAS<a class="elsevierStyleCrossRef" href="#bib0160">15</a> study in what concerns AMD improvement were comparable to those of the CATT<a class="elsevierStyleCrossRef" href="#bib0120">7</a> study. In addition, the treat and extend approach has demonstrated better VA results associated to a higher number of injections but with less visits than with the on-demand approach.<a class="elsevierStyleCrossRef" href="#bib0165">16</a> However, additional studies are required to verify whether the efficacy of this strategy is comparable to that of a fixed monthly administration of ranibizumab.The results obtained in the present study, comparing the above described methods of recovered VA percentage indicate that, even if patients make monthly follow-up visits and are retreated in case of relapse, the PRN regimen is unable to prevent the reactivation of AMD, with VA impairment in the majority of cases. If the VA loss occurs in the month prior to treatment, VA recovery is better (70% method 1) than in cases in which the VA loss occurs over one month after the last retreatment (43% method 2). This confirms the results of the SUSTAIN study<a class="elsevierStyleCrossRef" href="#bib0170">17</a> which observed that, with a smaller interval between VA losses and treatment, VA recovery is larger. It also confirms the results of the CATT study<a class="elsevierStyleCrossRef" href="#bib0120">7</a> which observed that efficacy diminishes after one year of fixed monthly treatment when switching to a PRN treatment regimen during the second year. In a PRN regimen, retreatments are administered only when the neovascular disease has effectively reactivated, and for this reason this approach is unable to avoid exudative recurrences.The main limitation of the present study is its retrospective nature, based on collecting clinical records data instead of interviewing patients, and this precludes the obtention of some data. Additional limitations include the single center nature of the study and the limited sample size of only 128 patients. Longitudinal studies in daily clinical practice, comparing both the therapeutic approaches, i.e., on-demand and proactive, would provide more precise information that could be useful not only from the clinical viewpoint but also for patients, specifically quality of life.ConclusionThe objective for treating neovascular AMD should be the prevention of relapses that could produce irreversible lesions in terms of VA. The results of the present study match the hypothesis that a reactive (on-demand) strategy is not sufficient for maintaining or recovering VA in neovascular AMD cases.Conflict of interestsRoberto Gallego-Pinazo is a Novartis consultant, and speaker for Novartis, Bayer, Carl Zeiss Meditec, Bloss and Heidelberg Engineering, and has received subsidies from Novartis, Bayer, Thea, Sensimed, Allergan, Alcon and Angelini, and per diem from Novartis, Bayer, Bloss and Heidelberg Engineering.Rosa Dolz-Marco is a speaker for Novartis, Bloss and Heidelberg Engineering. She has received subsidies from Novartis, Bayer, Thea, Sensimed, Allergan, Alcon and Angelini, and per diem from Novartis, Bloss and Heidelberg Engineering.María Andreu-Fenoll has received subsidies from Novartis, Bayer, Thea, Sensimed, Allergan, Alcon and Angelini, and per diem from Novartis and IMEX.Jordi Farres and Laura Monclús are employed by Bayer.All the authors state that there is no conflict of interests in relation to the publication of this article." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres807362" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec805260" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres807363" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec805259" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0025" "titulo" => "General visual results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Percentage of recovered visual acuity after a loss of five letters" ] ] ] ] ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 11 => array:2 [ "identificador" => "xack270405" "titulo" => "Acknowledgments" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-06-01" "fechaAceptado" => "2016-08-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec805260" "palabras" => array:6 [ 0 => "Neovascular AMD" 1 => "PRN regimen" 2 => "Treat-and-extend regimen" 3 => "Ranibizumab" 4 => "Visual acuity" 5 => "Re-treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec805259" "palabras" => array:6 [ 0 => "Degeneración macular asociada" 1 => "Protocolo Pro Re Nata" 2 => "Pauta «tratar y extender»" 3 => "Ranibizumab" 4 => "Agudeza visual" 5 => "Retratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo analyze the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD). Material and methodsAn observational, retrospective, single-center study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament. ResultsThe analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery. ConclusionsA PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoConocer el porcentaje de recuperación funcional, según estrategia pro re nata (PRN) con inyecciones intravítreas con ranibizumab en pacientes con degeneración macular asociada a la edad (DMAE). Material y métodosEstudio observacional, retrospectivo, unicéntrico. Se incluyó a pacientes con DMAE tratados con ranibizumab según estrategia PRN y seguimiento mínimo de 18 meses. Se recogieron variables sociodemográficas y clínicas de la historia clínica. El porcentaje de recuperación de agudeza visual (AV) después de perder 5 o más letras fue calculado considerando la AV del mes anterior, así como la mejor AV previa al retratamiento. ResultadosSe analizó a 128 pacientes. La media (DE) de seguimiento fue de 18,9 (2,3) meses; la media (DE) entre los primeros síntomas y el diagnóstico y entre la prescripción e inicio de tratamiento fue de 50,2 (57,4) y 10,9 (16,0) días, respectivamente.Ranibizumab solo fue prescrito en 108 pacientes tras una pérdida de 5 o más letras de AV.La media (DE) de recuperación de AV al considerar la AV de la última visita fue 70,3% (114,4). La media (DE) de recuperación de AV considerando la mejor AV antes del retratamiento fue de 43,5 (112,9), con un 59,4% de retratamientos que presentaron una recuperación de AV inferior al 75%, mientras que el 11,7% no presentaron recuperación de la AV. ConclusionesUna estrategia PRN con inyecciones intravítreas de ranibizumab podría no ser lo suficientemente efectiva en términos de mantenimiento o recuperación de AV en los casos de DMAE a largo plazo, debido a la pérdida irreversible de AV." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Gallego-Pinazo R, Dolz-Marco R, Andreu-Fenoll M, Farrés J, Monclús L. Impacto funcional del tratamiento con ranibizumab bajo una estrategia reactiva en pacientes con degeneración macular asociada a la edad exudativa neovascular. Arch Soc Esp Oftalmol. 2017;92:120–127." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This paper was partially presented at the 2016 Annual Congress of the American Society of Retina Specialists (ASRS) in San Francisco (California, United States)." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1330 "Ancho" => 2811 "Tamanyo" => 180112 ] ] "descripcion" => array:1 [ "en" => "Description of the methods applied for obtaining VA recovery after retreatment." ] ] 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" => 1464 "Tamanyo" => 161131 ] ] "descripcion" => array:1 [ "en" => "Changes in VA (%) during the entire follow-up period. Changes in VA during the entire follow-up period (from 3 to 18 months), in percentages (%)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 851 "Ancho" => 1534 "Tamanyo" => 71167 ] ] "descripcion" => array:1 [ "en" => "Percentage of recovered VA after retreatment." ] ] 3 => 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:2 [ "leyenda" => "Values are shown as n (%)." "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" 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">Total (No.=128) \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="2" align="left" valign="top">Unilateral or bilateral</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unilateral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">126 (98.4) \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">Bilateral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Studied eye</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Right \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 (44.4) \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">Left \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 (55.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Type of lesion</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidden \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 (54.7) \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">Classic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 (17.2) \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">Angiomatous retinal proliferation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (19.5) \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">Polypoid choroidal vasculopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (8.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Size of lesion</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><1 disc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (12.5) \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">1–2 discs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (31.3) \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">>2 discs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 (56.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Location of lesion</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subfoveal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81 (63.3) \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">Juxtafoveal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 (30.5) \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">Extrafoveal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (4.7) \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">Juxtapapillary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Thickness (microns) of foveal retina</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">367.3 (142.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Mean thickness (microns) of macula</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">296.6 (52.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Presence of symptoms at diagnostic</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">128 (100) \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">No \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></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354808.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline clinic characteristics of included patients with age-related macular degeneration." ] ] 4 => 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:1 [ "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" 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">Total (No.=128) n (%) \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">Extra foveal chorioretinal atrophy plates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 (24.2) \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">Foveal chorioretinal atrophy plates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (9.4) \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">Low density subretinal fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (78.1) \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">High density subretinal fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 (25.0) \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">Cystic intraretinal fluid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 (42.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354810.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Description (%) of clinical findings at diagnostic." ] ] 5 => 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:1 [ "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" 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">Month 3 No.=128 \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">Month 6 No.=128 \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">Month 12 No.=128 \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">Month 18 No.=128 \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="5" align="left" valign="top">Lesion size, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><1 disc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (11.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (11.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (10.9) \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">1–2 discs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49 (38.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49 (38.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47 (36.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 (42.2) \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">>2 discs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64 (50.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62 (48.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66 (51.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 (46.9) \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">p for symmetry against baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.2464 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.1504 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.6195 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0302 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Thickness of foveal retina center</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">263.6 (62.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">263.74 (59.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">258.41 (56.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">264.07 (64.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Changes of foveal retina thickness at center vis-à-vis baseline</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">104.59 (150.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">105.43 (158.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">112.7 (152.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">101.3 (143.4) \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">Student t-test for paired data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Mean macular thickness during follow-up</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">265.4 (31.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">270.3 (27.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">265.4 (28.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">264.6 (25.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Mean macula thickness changes against baseline.</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32.0 (48.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27.0 (51.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31.3 (49.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.8 (49.3) \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">Student t-test, paired data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354807.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Description of lesion, thickness and visual acuity of patients during follow-up at 3, 6, 12 and 18 months." ] ] 6 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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">Method 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">Method 2 \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">No.=108 \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">No.=162 \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="3" align="left" valign="top">VA loss in number of letters</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.51 (15.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.15 (13.16) \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">Number of re-treatments with loss equal to 0 (not included in the 108 subjects) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">VA gain in number of letters</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.59 (12.94) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.96 (12.88) \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">Number of retreatments with gain equal to 0 (not included in the 108 subjects) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">VA recovery percentage in number of letters (continuous)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Median (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.03 (114.37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.52 (112.86) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">VA recovery percentage and number of letters (categoric)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><0% (highest impairment) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (12.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 (11.7) \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">0–24% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (19.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 (23.5) \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">25–49% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (6.8) \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">50–74% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (12.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (12.3) \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">75–99% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (6.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (5.6) \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">100–124% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 (28.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (29.6) \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">≥125% (highest improvement) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (10.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1354809.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Description of visual acuity loss, gain and recovery percentage in letters with retreatments: comparison with method 1 and method 2." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0090" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/21735794/0000009200000003/v1_201703010038/S2173579416301591/v1_201703010038/en/main.assets" "Apartado" => array:4 [ "identificador" => "5816" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735794/0000009200000003/v1_201703010038/S2173579416301591/v1_201703010038/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579416301591?idApp=UINPBA00004N"]

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Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration

Impacto funcional del tratamiento con ranibizumab bajo una estrategia reactiva en pacientes con degeneración macular asociada a la edad exudativa neovascular

R. Gallego-Pinazoa,b,c,

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robertogallego@comv.es

Corresponding author.

, R. Dolz-Marcob,c, M. Andreu-Fenollb,c, J. Farrésd, L. Monclúsd

a Unidad de Mácula, Servicio de Oftalmología, Hospital Universitario y Politécnico La Fe, Valencia, Spain

b RETICS RD160008 Enfermedades oculares, Prevención, detección precoz, tratamiento y rehabilitación de las enfermedades oculares, Spain

c Instituto de Investigaciones Sanitarias La Fe, Hospital Universitario y Politécnico La Fe, Valencia, Spain

d Bayer Hispania, Barcelona, Spain

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alternative dosage strategies have been considered for said treatments to produce the same efficacy but with a lower number of visits and injections&#46; The first was the injection on-demand regime or <span class="elsevierStyleItalic">pro re nata</span> &#40;PRN&#41;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">7&#44;8</span></a> according to which&#44; after an initial dosage during the first 3 months&#44; strictly monthly visits are prescribed to administer retreatments on the basis of VA or changes in optical coherence tomography &#40;OCT&#41;&#46; However&#44; this strategy does not diminish the number of visits as patients must undergo an examination every 4 weeks to detect relapses at an early stage&#44; and accordingly the burden on health services remains high&#46; The Comparison made by the Age-Related macular Degeneration Treatment Trials &#40;CATT&#41; study demonstrated that the PRN strategy is inferior in efficacy to monthly treatment and that&#44; even after one year of monthly treatment&#44; efficacy diminishes when changing the regimen to reactive treatment in the second year&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The Inhibit VEGF in Age-Related Choroidal Neovascularisation &#40;IVAN&#41; study analyzed a different retreatment strategy consisting in injections during 3 consecutive months after a relapse&#46; Even so&#44; diminished VA could not be recovered after the reactivation and the VA results with this PRN regimen did not demonstrate to be equal to those obtained with a fixed treatment regimen&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The irreversible deterioration of vision&#44; which is apparently intrinsic to the PRN treatment regimen&#44; entails the impossibility of strict monthly follow-ups in daily clinical practice&#46; Accordingly&#44; the effectiveness of the on-demand prescription is even lower despite experiencing initial VA improvements because these cannot be maintained due to longer periods between visits and to diminished treatment dosages throughout the follow-up period&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A further follow-up strategy proposes that treatment should not be made when recurrences are detected&#59; instead&#44; the treatment should be administrated previously&#46; This is known as &#8220;treat and extend&#8221; treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Some authors have observed that eventual visual losses associated to the reactivation of the neovascular lesion during a PRN follow-up do not recover completely even when treatment is administrated&#44; and indicate 53&#8211;67&#37; of restoration of vision in the subgroup of patients who lost over 5 letters&#46; Accordingly&#44; treatment should be proactive in order to avoid or stretch out in time relapses of existing lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">11&#44;12</span></a> It can be seen that the strategy for treating and following up patients with neovascular AMD remains an open debate in a search to achieve more efficient management of antiangiogenic medicaments in daily practice&#44; which is generally burdened with excessive workloads&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In-depth knowledge about the evolution of the disease and its response to on-demand or reactive treatment &#40;the most widely utilized at present&#41; is essential to optimize the approach to this disease&#46; The objective of the present study is to assess the functional recovery percentage after visual loss in a PRN follow-up with ranibizumab in patients with neovascular AMD followed up in a single hospital specialized in this disease by a single retina specialist&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">An observational&#44; retrospective and single center study &#40;EPA-RE&#41; in patients fulfilling the following criteria&#58; &#40;1&#41; new neovascular AMD diagnostic and at least 18 months of follow-up in the hospital&#59; &#40;2&#41; treatment with ranibizumab with on-demand regimen with frequent checkups and retreatments in the presence of any intra-or subretinal fluid in OCT and VA loss of at least one decimal fraction&#59; &#40;3&#41; patients with medical records and information since AMD was diagnosed at the hospital&#46; Clinic record reviews were carried out in the Macula Unit of the University and Polytechnic Hospital La Fe of Valencia&#44; and included the records of patients in consecutive order from diagnostic date to avoid selection bias&#46; The retrospective observation period was 18 months&#46; The eye of the study was the one which had at least 18 months treatment with ranibizumab and&#44; in case of bilateral involvement&#44; the first diagnosed eye or the one with better VA if both had been diagnosed at the same time&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The study was approved by the Medicaments Agency of Spain and the Ethical Committee of the University Hospital La Fe of Valencia&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Sociodemographic data were collected &#40;age&#44; sex&#44; race&#44; color of eyes and tobacco smoking&#41; as well as clinical data &#40;diagnostic date&#44; affected eye&#44; lesion size&#44; retinal and foveal thickness&#41; of the patients included in the study through the clinic records or other source documents&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The analysis of the main objective was focused on estimating the VA &#40;recovery percentage assessed by means of the Snellen test&#41; after retreatments&#46; Two different methods were applied in order to calculate VA after retreatments &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Method 1&#58; VA recovery percentage<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#40;VA recovered after treatment&#47;VA lost prior to treatment&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#44; where&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">VA recovered after treatment</span> was defined as the difference between the best VA achieved during the 3 months after retreatment and that recorded at the visit that gave rise to the retreatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">VA lost prior to treatment</span> was defined as the difference between the VA achieved in the previous visit that gave rise to the retreatment and the VA recorded at the retreatment visit&#46;</p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">Method 2&#58; VA recovery percentage&#58; &#40;VA recovered after treatment&#47;VA lost prior to treatment&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#44; where&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">VA recovered after treatment</span> was defined as the difference between the best VA achieved during the 3 months after retreatment and that recorded at the visit that gave rise to the retreatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">VA lost prior to retreatment</span> was defined as the difference between the best VA achieved during follow-up between the previous dose and that of retreatment&#44; and VA achieved at the retreatment visit&#46;</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The clinic and sociodemographic data were submitted to a descriptive analysis&#44; analyzing the evolution of clinical variables &#40;retinal thickness&#44; clinic results&#44; VA and concomitant ophthalmological diseases&#41; by means of the Student <span class="elsevierStyleItalic">t</span>-test&#46; All the continuous variables were analyzed as mean&#44; standard deviation &#40;SD&#41;&#44; maximum and minimum recorded values&#44; median and quartiles&#46; A significance value of 0&#46;05 was taken into account in all cases&#46; The statistical analysis was carried out with the SAS application version 9&#46;2 &#40;SAS Institute Inc&#46;&#44; Cary&#44; NC&#44; USA&#41; in Windows&#8482; &#40;SAS Institute Inc&#46; 2008&#46; SAS&#47;STAT<span class="elsevierStyleSup">&#174;</span>9&#46;2 User&#39;s Guide&#46; Cary&#44; NC&#58; SAS Institute Inc&#46; Copyright &#169; 2008&#46; SAS Institute Inc&#46;&#44; Cary&#44; NC&#44; USA&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">Overall&#44; the study included 150 patients of which 128 were assessable while 22 patients did not have recorded retreatments due to loss of VA during the follow-up period&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The mean follow-up of patients was 18&#46;9 &#40;SD 2&#46;3&#41; months&#46; The sample comprised 60&#46;2&#37; of females and 38&#46;2&#37; of males&#44; with a mean age of 76&#46;0 &#40;SD 8&#46;8&#41; years&#46; Virtually all patients &#40;98&#46;4&#37;&#41; exhibited at diagnostic unilateral compromise caused by neovascular AMD&#46; In 55&#46;6&#37; of cases the studied eye was the left &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Overall&#44; 62&#46;5&#37; of patients reported sudden and progressive VA reduction at diagnostic&#46; Only 50 of the 128 patients included in the study had data recorded in their clinical records indicating the time elapsed between the first symptoms and the AMD diagnostic&#44; with a mean age of &#40;SD 57&#46;4&#41; days&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The mean number of visits was 12&#46;5 &#40;SD 3&#46;1&#41;&#44; with an interval of 50&#8211;20 visits&#46; Regarding the location of the neovascular lesion&#44; the most frequent was subfoveal &#40;63&#46;3&#37;&#41;&#44; followed by juxtapapillar &#40;30&#46;5&#37;&#41;&#46; The number of visits was significantly higher for patients with subfoveal lesions &#40;48&#46;4 &#91;SD 39&#46;5&#93; days&#41; against those with juxtapapillar lesions &#40;41&#46;9 &#91;SD 18&#46;5&#93; days&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41;&#46; Approximately 80&#37; of patients exhibited lesions between 1 and 2 or over 2 optic discs&#46; In what concerns size changes and comparison with the baseline&#44; statistically significant differences were observed after 18 months &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0302&#41;&#46; No statistically significant differences were observed in the number or frequency of visits or lesion location at diagnostic&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In what concerns the morphological classic patient of neovascular lesions based on OCT&#44; 54&#46;7&#37; were type I lesions &#40;hidden&#41;&#44; 19&#46;5&#37; were type III &#40;retinal angiomatous proliferation&#41;&#44; 17&#46;2&#37; were type II &#40;classic&#41; and 6&#46;8&#37; were identified as polypoid choroidal vasculopathy&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the clinic results observed most frequently at diagnostic&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes the evolution of macular and retinal thickness at each follow-up period in comparison with baseline&#46; Statistically significant differences were observed in comparison with the baseline period &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; for both the variables and these remained similar throughout the follow-up period&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">The mean of 10&#46;9 days and a median of 4 days elapsed between prescription and the first administration of ranibizumab&#44; and in 68&#46;0&#37; of cases the first treatment was administered a few days after the baseline period&#46; During the follow-up period&#44; patients received a mean &#40;min&#46;&#44; max&#46;&#41; of 6&#46;0 &#40;1&#44; 14&#41; and a median of 5 treatments&#46; The most frequent reason for receiving treatment was the reappearance&#47;persistence of subretinal fluid &#40;71&#46;9&#37;&#41;&#44; followed by initial treatment &#40;57&#46;8&#37;&#41; and reappearance&#47;persistence of intraretinal fluid &#40;57&#46;0&#37;&#41;&#46; In all 128 included patients&#44; the mean &#40;SD&#41; number of visits was 12&#46;5 &#40;3&#46;1&#41; and the median of 12&#46;5&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">General visual results</span><p id="par0120" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> compares changes in VA in terms of patient percentages during the follow-up period where&#44; in the baseline situation&#44; the mean VA was 43&#46;79 &#40;SD 22&#46;6&#41; letters&#44; and during the follow-up periods it improved with a mean VA after eighteen months of 53&#46;2 &#40;SD 22&#46;4&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Percentage of recovered visual acuity after a loss of five letters</span><p id="par0125" class="elsevierStylePara elsevierViewall">The results for loss&#44; gain and percentage of VA recovery in letters were analyzed with the two methods described above&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> compares both methods and the percentage of recovered VA after retreatment with both methods&#58;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Method 1&#58; 108 retreatments due to recurring exudative signs associated to visual deterioration of five or more letters that had all the information to calculate the VA recovery percentage&#46; Said 108 retreatments exhibited a mean VA loss of 10&#46;5 &#40;SD 15&#46;7&#41; letters before retreatment&#46; However&#44; the mean gain observed after retreatment was 7&#46;59 &#40;SD 12&#46;94&#41; letters&#44; corresponding to the mean VA recovery percentage of 70&#46;03&#37; &#40;SD 114&#46;37&#41; when compared to VA before retreatment&#46; In this case&#44; forty-eight percent of retreatments exhibited a recovery percentage below 75&#37;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Method 2&#58; 162 retreatments were registered due to recurring exudative signs associated to visual impairment of 5 or more letters having information for calculating the VA recovery percentage&#46; Said 162 retreatments exhibited a mean loss of 15&#46;1 &#40;SD 13&#46;2&#41; letters prior to retreatment and the mean gain after retreatment of 7&#46;96 &#40;SD 12&#46;88&#41; letters&#44; corresponding to a mean VA recovery of 43&#46;5&#37; when comparing between the best reported VA and the last initial dose or the previous retreatment&#46; Overall&#44; 54&#46;3&#37; of retreatments exhibited a VA recovery percentage below 75&#37;&#46;</p></span></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">Even in the absence of any scientific evidence demonstrating that PRN regimes are equivalent to fixed regimes&#44; the need to reduce the amount of visits influence the adoption of this strategy in clinical practice&#46; It is necessary to delve deeper in the knowledge of the disease and in the respondents of the &#8220;reactive or on-demand PRN&#8221; with anti-VEGF agents in order to design improved therapeutic approaches for AML&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Some studies have demonstrated that ranibizumab is effective in a fixed monthly treatment regimen with a VA recovery of 7&#46;2 and 11&#46;3 letters at 12 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">4&#44;5</span></a> The problem associated to this high efficiency strategy is that it involves a high number of visits and injections which are difficult to apply in clinical practice&#46; In addition&#44; it could be considered that some patients are overtreated with a fixed monthly treatment regimen&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">As an alternative&#44; some studies reported modification of said regimen utilizing the so-called on-demand strategy or PRN which carries out retreatments only on the basis of OCT parameters or diminished VA&#46; This strategy is more individualized but its disadvantage is that it requires strict monthly follow-up visits to minimize vision impairment with each reactivation of the disease&#46; Accordingly&#44; even though the number of injections can be diminished in some cases&#44; it is necessary to maintain the number of follow-up visits&#44; making this regimen a highly expensive and difficult to apply approach in hospitals with high workloads&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> In addition&#44; the results provided in the IVAN&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a> CATT<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> and HARBOR<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> studies demonstrated that the functional and anatomical efficacy of PRN regimes did not reach the efficacy achieved by the monthly administration regimes&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The appearance of the <span class="elsevierStyleItalic">treat and extend</span> regimen provides an alternative to treat patients with neovascular AMD without waiting for a relapse&#44; progressively increasing intervals between visits&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">11&#44;14</span></a> This enables a workload reduction and avoids patient overtreatment&#46; Conceptually&#44; the functional results of this strategy should be better than those provided by the PRN regimes&#44; as the treatment anticipates relapses and endeavors to avoid them&#46; The results of the LUCAS<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> study in what concerns AMD improvement were comparable to those of the CATT<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> study&#46; In addition&#44; the <span class="elsevierStyleItalic">treat and extend</span> approach has demonstrated better VA results associated to a higher number of injections but with less visits than with the on-demand approach&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> However&#44; additional studies are required to verify whether the efficacy of this strategy is comparable to that of a fixed monthly administration of ranibizumab&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The results obtained in the present study&#44; comparing the above described methods of recovered VA percentage indicate that&#44; even if patients make monthly follow-up visits and are retreated in case of relapse&#44; the PRN regimen is unable to prevent the reactivation of AMD&#44; with VA impairment in the majority of cases&#46; If the VA loss occurs in the month prior to treatment&#44; VA recovery is better &#40;70&#37; method 1&#41; than in cases in which the VA loss occurs over one month after the last retreatment &#40;43&#37; method 2&#41;&#46; This confirms the results of the SUSTAIN study<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a> which observed that&#44; with a smaller interval between VA losses and treatment&#44; VA recovery is larger&#46; It also confirms the results of the CATT study<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> which observed that efficacy diminishes after one year of fixed monthly treatment when switching to a PRN treatment regimen during the second year&#46; In a PRN regimen&#44; retreatments are administered only when the neovascular disease has effectively reactivated&#44; and for this reason this approach is unable to avoid exudative recurrences&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The main limitation of the present study is its retrospective nature&#44; based on collecting clinical records data instead of interviewing patients&#44; and this precludes the obtention of some data&#46; Additional limitations include the single center nature of the study and the limited sample size of only 128 patients&#46; Longitudinal studies in daily clinical practice&#44; comparing both the therapeutic approaches&#44; i&#46;e&#46;&#44; on-demand and proactive&#44; would provide more precise information that could be useful not only from the clinical viewpoint but also for patients&#44; specifically quality of life&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0170" class="elsevierStylePara elsevierViewall">The objective for treating neovascular AMD should be the prevention of relapses that could produce irreversible lesions in terms of VA&#46; The results of the present study match the hypothesis that a reactive &#40;on-demand&#41; strategy is not sufficient for maintaining or recovering VA in neovascular AMD cases&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interests</span><p id="par0175" class="elsevierStylePara elsevierViewall">Roberto Gallego-Pinazo is a Novartis consultant&#44; and speaker for Novartis&#44; Bayer&#44; Carl Zeiss Meditec&#44; Bloss and Heidelberg Engineering&#44; and has received subsidies from Novartis&#44; Bayer&#44; Thea&#44; Sensimed&#44; Allergan&#44; Alcon and Angelini&#44; and <span class="elsevierStyleItalic">per diem</span> from Novartis&#44; Bayer&#44; Bloss and Heidelberg Engineering&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Rosa Dolz-Marco is a speaker for Novartis&#44; Bloss and Heidelberg Engineering&#46; She has received subsidies from Novartis&#44; Bayer&#44; Thea&#44; Sensimed&#44; Allergan&#44; Alcon and Angelini&#44; and <span class="elsevierStyleItalic">per diem</span> from Novartis&#44; Bloss and Heidelberg Engineering&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Mar&#237;a Andreu-Fenoll has received subsidies from Novartis&#44; Bayer&#44; Thea&#44; Sensimed&#44; Allergan&#44; Alcon and Angelini&#44; and <span class="elsevierStyleItalic">per diem</span> from Novartis and IMEX&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Jordi Farres and Laura Moncl&#250;s are employed by Bayer&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">All the authors state that there is no conflict of interests in relation to the publication of this article&#46;</p></span></span>"
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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 analyze the functional recovery using a <span class="elsevierStyleItalic">pro re nata</span> &#40;PRN&#41; dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration &#40;AMD&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An observational&#44; retrospective&#44; single-center study&#44; was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab&#44; and were followed-up for a minimum of 18 months&#46; Sociodemographic and clinical data were collected from medical records&#46; The percentage of visual acuity &#40;VA&#41; recovered after losing 5 or more letters was calculated taking into account the previous visit&#44; as well as considering the best VA recorded prior to the retreament&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The analysis included 128 patients&#46; The mean &#40;SD&#41; follow-up period was 18&#46;9 &#40;2&#46;3&#41; months&#46; The mean &#40;SD&#41; elapsed days between onset of symptoms and diagnosis&#44; and between prescription and administration of treatment was 50&#46;2 &#40;57&#46;4&#41; and 10&#46;9 &#40;16&#46;0&#41;&#44; respectively&#46; Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA&#46; The mean &#40;SD&#41; VA recovery compared to the previous VA was 70&#46;3&#37; &#40;114&#46;4&#41;&#46; On the other hand&#44; the mean &#40;SD&#41; VA recovery when considering the best VA registered before the retreatment was 43&#46;5&#37; &#40;112&#46;9&#41;&#44; with 59&#46;4&#37; of re-treatments having a VA recovery below 75&#37;&#44; and with 11&#46;7&#37; not presenting any VA recovery&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and&#47;or recovering VA in the long-term&#44; due to a cumulative irreversible VA loss&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and 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">Conocer el porcentaje de recuperaci&#243;n funcional&#44; seg&#250;n estrategia <span class="elsevierStyleItalic">pro re nata</span> &#40;PRN&#41; con inyecciones intrav&#237;treas con ranibizumab en pacientes con degeneraci&#243;n macular asociada a la edad &#40;DMAE&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional&#44; retrospectivo&#44; unic&#233;ntrico&#46; Se incluy&#243; a pacientes con DMAE tratados con ranibizumab seg&#250;n estrategia PRN y seguimiento m&#237;nimo de 18 meses&#46; Se recogieron variables sociodemogr&#225;ficas y cl&#237;nicas de la historia cl&#237;nica&#46; El porcentaje de recuperaci&#243;n de agudeza visual &#40;AV&#41; despu&#233;s de perder 5 o m&#225;s letras fue calculado considerando la AV del mes anterior&#44; as&#237; como la mejor AV previa al retratamiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se analiz&#243; a 128 pacientes&#46; La media &#40;DE&#41; de seguimiento fue de 18&#44;9 &#40;2&#44;3&#41; meses&#59; la media &#40;DE&#41; entre los primeros s&#237;ntomas y el diagn&#243;stico y entre la prescripci&#243;n e inicio de tratamiento fue de 50&#44;2 &#40;57&#44;4&#41; y 10&#44;9 &#40;16&#44;0&#41; d&#237;as&#44; respectivamente&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Ranibizumab solo fue prescrito en 108 pacientes tras una p&#233;rdida de 5 o m&#225;s letras de AV&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La media &#40;DE&#41; de recuperaci&#243;n de AV al considerar la AV de la &#250;ltima visita fue 70&#44;3&#37; &#40;114&#44;4&#41;&#46; La media &#40;DE&#41; de recuperaci&#243;n de AV considerando la mejor AV antes del retratamiento fue de 43&#44;5 &#40;112&#44;9&#41;&#44; con un 59&#44;4&#37; de retratamientos que presentaron una recuperaci&#243;n de AV inferior al 75&#37;&#44; mientras que el 11&#44;7&#37; no presentaron recuperaci&#243;n de la AV&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Una estrategia PRN con inyecciones intrav&#237;treas de ranibizumab podr&#237;a no ser lo suficientemente efectiva en t&#233;rminos de mantenimiento o recuperaci&#243;n de AV en los casos de DMAE a largo plazo&#44; debido a la p&#233;rdida irreversible de AV&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gallego-Pinazo R&#44; Dolz-Marco R&#44; Andreu-Fenoll M&#44; Farr&#233;s J&#44; Moncl&#250;s L&#46; Impacto funcional del tratamiento con ranibizumab bajo una estrategia reactiva en pacientes con degeneraci&#243;n macular asociada a la edad exudativa neovascular&#46; Arch Soc Esp Oftalmol&#46; 2017&#59;92&#58;120&#8211;127&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This paper was partially presented at the 2016 Annual Congress of the American Society of Retina Specialists &#40;ASRS&#41; in San Francisco &#40;California&#44; United States&#41;&#46;</p>"
      ]
    ]
    "multimedia" => array:7 [
      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" => 1330
            "Ancho" => 2811
            "Tamanyo" => 180112
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Description of the methods applied for obtaining VA recovery after retreatment&#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"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Changes in VA &#40;&#37;&#41; during the entire follow-up period&#46; Changes in VA during the entire follow-up period &#40;from 3 to 18 months&#41;&#44; in percentages &#40;&#37;&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Percentage of recovered VA after retreatment&#46;</p>"
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      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Values are shown as n &#40;&#37;&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "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" 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">Total &#40;No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&#41;&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="2" align="left" valign="top"><span class="elsevierStyleItalic">Unilateral or bilateral</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>Unilateral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">126 &#40;98&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bilateral&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;1&#46;6&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Studied eye</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>Right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56 &#40;44&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70 &#40;55&#46;6&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Type of lesion</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>Hidden&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70 &#40;54&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Classic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22 &#40;17&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Angiomatous retinal proliferation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;19&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polypoid choroidal vasculopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;8&#46;6&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Size of lesion</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>&#60;1 disc&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;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1&#8211;2 discs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40 &#40;31&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#62;2 discs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72 &#40;56&#46;3&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Location of lesion</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>Subfoveal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81 &#40;63&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Juxtafoveal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39 &#40;30&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Extrafoveal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Juxtapapillary&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;1&#46;6&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Thickness &#40;microns&#41; of foveal retina</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">367&#46;3 &#40;142&#46;2&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Mean thickness &#40;microns&#41; of macula</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">296&#46;6 &#40;52&#46;9&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Presence of symptoms at diagnostic</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>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">128 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No&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></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Baseline clinic characteristics of included patients with age-related macular degeneration&#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" 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">Total &#40;No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&#41;<br>n &#40;&#37;&#41;&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">Extra foveal chorioretinal atrophy plates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31 &#40;24&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Foveal chorioretinal atrophy plates&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;9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low density subretinal fluid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100 &#40;78&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High density subretinal fluid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;25&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystic intraretinal fluid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54 &#40;42&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Description &#40;&#37;&#41; of clinical findings at diagnostic&#46;</p>"
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at3"
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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="" 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">Month 3<br>No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&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">Month 6<br>No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&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">Month 12<br>No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&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">Month 18<br>No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&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="5" align="left" valign="top"><span class="elsevierStyleItalic">Lesion size&#44; n &#40;&#37;&#41;</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>&#60;1 disc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;11&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;11&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;10&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1&#8211;2 discs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49 &#40;38&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49 &#40;38&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47 &#40;36&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54 &#40;42&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#62;2 discs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64 &#40;50&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62 &#40;48&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66 &#40;51&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60 &#40;46&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>p for symmetry against baseline&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;2464&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;1504&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;6195&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;0302&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Thickness of foveal retina center</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">263&#46;6 &#40;62&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">263&#46;74 &#40;59&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">258&#46;41 &#40;56&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">264&#46;07 &#40;64&#46;2&#41;&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Changes of foveal retina thickness at center vis-&#224;-vis baseline</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">104&#46;59 &#40;150&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">105&#46;43 &#40;158&#46;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">112&#46;7 &#40;152&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">101&#46;3 &#40;143&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Student <span class="elsevierStyleItalic">t</span>-test for paired data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Mean macular thickness during follow-up</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">265&#46;4 &#40;31&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">270&#46;3 &#40;27&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">265&#46;4 &#40;28&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">264&#46;6 &#40;25&#46;8&#41;&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="5" 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="5" align="left" valign="top"><span class="elsevierStyleItalic">Mean macula thickness changes against baseline&#46;</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32&#46;0 &#40;48&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;0 &#40;51&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;3 &#40;49&#46;2&#41;&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;8 &#40;49&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Student <span class="elsevierStyleItalic">t</span>-test&#44; paired data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "etiqueta" => "Table 4"
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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="" 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">Method 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">Method 2&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">No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>108&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">No&#46;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>162&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="3" align="left" valign="top"><span class="elsevierStyleItalic">VA loss in number of letters</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;51 &#40;15&#46;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;15 &#40;13&#46;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of re-treatments with loss equal to 0 &#40;not included in the 108 subjects&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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="3" 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="3" align="left" valign="top"><span class="elsevierStyleItalic">VA gain in number of letters</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>Median &#40;SD&#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&#46;59 &#40;12&#46;94&#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&#46;96 &#40;12&#46;88&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of retreatments with gain equal to 0 &#40;not included in the 108 subjects&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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="3" 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="3" align="left" valign="top"><span class="elsevierStyleItalic">VA recovery percentage in number of letters &#40;continuous&#41;</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>Median &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&#46;03 &#40;114&#46;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;52 &#40;112&#46;86&#41;&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="3" 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="3" align="left" valign="top"><span class="elsevierStyleItalic">VA recovery percentage and number of letters &#40;categoric&#41;</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>&#60;0&#37; &#40;highest impairment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;12&#46;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">19 &#40;11&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>0&#8211;24&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;19&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38 &#40;23&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 21735794
Original language: English

DOI:10.1016/j.oftale.2016.11.009

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2020 September	0	1	1
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2017 August	1	0	1

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