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OCT angiography biomarkers in type 1 choroidal neovascularisation after one year of aflibercept treatment
Biomarcadores de OCT-angiografía en la neovascularización coroidea tipo 1 tras tratamiento con aflibercept durante 1 año
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MAVC media basal: 29,05<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12,01. MAVC media en el mes<span class="elsevierStyleHsp" style=""></span>4: 43,93<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15,22. MAVC media en el mes<span class="elsevierStyleHsp" style=""></span>8: 42,80<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14,18. MAVC media en el mes<span class="elsevierStyleHsp" style=""></span>12: 44,23<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14,60.</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,0001 vs basal; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0226 vs mes 4; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0002 vs mes<span class="elsevierStyleHsp" style=""></span>8.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Campos Polo, I. Gómez Sánchez" "autores" => array:2 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Campos Polo" ] 1 => array:2 [ "nombre" => "I." 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Corticosteroids are the first-line therapeutic option for the treatment of OII. Depending on the severity of the inflammation, its course and location, clinicians should establish the route of administration, dose and dosage of treatment.</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">FA: fluorescein angiography; FAG: angiography with indocyanine green; PRP: panretinal photocoagulation; DXM: dexamethasone; IOI: intraocular inflammation; IV: intravenous; IVP: intravenous; mPRDL: methylprednisolone; OCT: optical coherence tomography; OCT-A: angio-OCT; RVO: retinal vascular occlusion; PRD: prednisone; PRDL: prednisolone; TACA: triamcinolone acetonide; RV: retinal vasculitis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Fonollosa, R. Gallego-Pinazo, L. Sararols, A. Adán, M. López-Gálvez, M.S. Figueroa" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Fonollosa" ] 1 => array:2 [ "nombre" => "R." 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"apellidos" => "Figueroa" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669122000818" "doi" => "10.1016/j.oftal.2022.02.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669122000818?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579422000846?idApp=UINPBA00004N" "url" => "/21735794/0000009700000011/v2_202301300805/S2173579422000846/v2_202301300805/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "OCT angiography biomarkers in type 1 choroidal neovascularisation after one year of aflibercept treatment" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "639" "paginaFinal" => "645" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "R. Campos Polo, I. Gómez Sánchez" "autores" => array:2 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Campos Polo" "email" => array:1 [ 0 => "rafacampospolo@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Gómez Sánchez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Retina, Hospital Virgen del Puerto, Plasencia, Cáceres, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Perpetuo Socorro, Badajoz, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Doutor José María Grande, ULSNA, Portalegre, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Biomarcadores de OCT-angiografía en la neovascularización coroidea tipo 1 tras tratamiento con aflibercept durante 1 año" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1305 "Ancho" => 1305 "Tamanyo" => 184892 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Structural OCT and OCTA images of patient number 2. a) Structural OCT image from the baseline visit showing a CNV type 1 and adjacent subretinal fluid. b) OCTA image from the baseline visit showing a sea fan CNV, presence of small capillaries and anastomoses in the branches, peripheral terminating arcade in terminal vessel and hypointense perilesional halo (active CNV). c) Structural OCT image from month 12 visit where flattening of the pigment epithelium and disappearance of subretinal fluid is seen. d) OCT image from month 12 visit where small capillaries and branch anastomoses have disappeared, the terminal vessel has a "dead tree" appearance and perilesional hypointense halo persists (inactive CNV).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The diagnosis of macular diseases has traditionally been made using retinography, fluorescein angiography, indocyanine green angiography and optical coherence tomography (OCT). The first OCT dates back to the early 1990s, and is currently the most widely used device for the diagnosis and monitoring of neovascular age-related macular degeneration (NAMD).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">OCT-angiography (OCTA) has revolutionised the study of AMD. It is a non-invasive technique that allows us to visualize retinal and choroidal vessels, which is especially interesting in choroidal neovascularization type 1 (CNV1) because it is located under the retinal pigment epithelium (RPE) and its visualization is complex with conventional multimodal imaging techniques.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Numerous studies have described the alterations produced by AMD-associated CNV1 at the level of the choriocapillaris, as well as the quantitative and qualitative biomarkers of its activity. Recently, the evolution of these biomarkers has also been assessed in patients with NAMD treated with anti-vascular endothelial growth factor (anti-VEGF) therapy; however, in most studies the follow-up time was short and, in addition, a wide variety of treatment regimens were used, which prevents us from drawing adequate conclusions.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This prospective study assessed the biomarkers of activity, both quantitative and qualitative, of CNV1 associated with AMD in <span class="elsevierStyleItalic">naïve</span> patients treated with aflibercept (Eylea®, Bayer Hispania S.L., Spain) during 12 months. The effectiveness of aflibercept in terms of visual acuity (VA) gain has also been evaluated and the relationship between biomarkers, and VA gain has been analyzed to try to identify which is associated with a better visual prognosis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A prospective, observational, non-interventional study of 12 months of follow-up (from January 2018 to January 2019) in which a cohort of 40 eyes of 33 patients diagnosed with NAMD who had associated CNV1 was studied. The inclusion criteria were: not having been previously treated with any anti-VEGF drug (<span class="elsevierStyleItalic">naïve</span> patient), not having signs of structural damage in the fovea (fibrosis or atrophy), not presenting vitreomacular traction and not having undergone any ocular intervention in the 6 months prior to the start of the study.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The baseline examination of each patient comprised best corrected visual acuity (BCVA) expressed in ETDRS letters and a complete examination (biomicroscopy, tonometry and funduscopy). A structural OCT was also performed, at each visit, to assess the evolution of central macular thickness (CMT) expressed in microns. The diagnosis of CNV1 was made by Swpet-Source OCT angiography (SS-OCTA) (DRI OCT Triton, Topcon Europe Medical BV, Capelle aan den Ijssel, The Netherlands), which was used to measure the size of the lesion as well as to study the characteristics of the neovascular network. The DRI OCT Triton platform uses the OCTARA™ (OCTA ratio analysis) algorithm; this technology analyzes vascular flow-derived changes using multiple OCT-B scans acquired at the same position and its acquisition speed is 100,000 scans per second. The ×6 6 mm, fovea-centered working protocol was used, and manual segmentation of the different retinal layers was performed to improve the visualization of choroidal neovascularization (CNV) and evaluate it with greater accuracy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Each CNV underwent both quantitative and qualitative analysis. The quantitative analysis consisted of manual size measurement at each visit, while the qualitative analysis was based on the study of biomarkers of CNV activity described by Coscas et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and Al-Sheikh et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>: a)shape, well-defined (cartwheel or sea fan) vs long filamentous vessels; b)ramifications, small capillaries vs long, mature vessels; c)presence vs absence of anastomoses; d)peripheral terminal arcade in terminal vessel vs "dead tree" appearance, and e)presence vs absence of perilesional hypointense halo. CNV was categorized as active if it had at least 3 of the 5 biomarkers described as active, and as quiescent otherwise.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The images were interpreted by two expert retinologists (RCP and IGS).</p><p id="par0040" class="elsevierStylePara elsevierViewall">Patients were treated with intravitreal aflibercept 2 mg/0.05 ml according to the technical data sheet,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> a loading dose of 3 injections followed by a fixed injection every 2 months until completing 1 year of treatment. In addition to the assessment at diagnosis, patients were evaluated in the practice at months 4, 8 and 12.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The Statistical Analysis Systems program (SAS Institute, Cary, NC, USA) version 9.4 was used for the statistical study, with a significance level of p < 0.05. Student's t-test was used to compare the evolution of continuous variables and a multivariate analysis was performed to analyze the relationship between VA gain and OCTA biomarkers; for this purpose, qualitative and quantitative variables were studied and confounding factors such as age, sex, and baseline VA were introduced. Quantitative variables were evaluated as continuous measures, while qualitative variables were evaluated as presence or absence of the characteristic.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study included 40 eyes of 33 patients. The mean age of the population was 82.3 ± 6.2 years (range 68-92), of whom 26 (78.8%) were female. The baseline BCVA was 52.0 ± 12.0 letters.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Baseline CMT was 447.08 ± 127.23 microns, which decreased 182.1 ± 117.37 microns at 4 months (p < 0.0001) and experienced minimal but not statistically significant changes at subsequent revisions. The reduction in CMT at 12 months was 185.68 ± 123.53 microns (p < 0.0001) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Regarding the quantitative OCTA findings, the mean basal area of CNV was found to be 2.5 ± 1.9 mm<span class="elsevierStyleSup">2</span>. The lesion area decreased 1.2 ± 1.0 mm<span class="elsevierStyleSup">2</span> by the fourth month (p < 0.0001), remaining stable thereafter. The total reduction in CNV area at 12 months was 1.2 ± 1.1 mm<span class="elsevierStyleSup">2</span>, a mean reduction of 47.7% from baseline (p < 0.0001) (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Regarding qualitative findings, CNV exhibited in all cases a well-defined pattern at baseline: 36 eyes (90%) a sea fan pattern and 4 (10%) a cartwheel pattern; these percentages remained stable throughout the study period (p = 1.000 at 12 months vs baseline). All eyes had numerous fine capillaries at baseline; the percentage of these decreased to 15% at month 4 (p < 0.0001) and remained unchanged until the end of the study. Accordingly, the reduction of this parameter was 85% at 12 months of follow-up (p < 0.0001 vs baseline). 100% had anastomoses at baseline, which decreased to 30% at month 4 (p < 0.0001) and remained unchanged until the end of follow-up (p < 0.0001 vs baseline). Before starting treatment all CNVs had a peripheral terminal arcade, but by month 4, 90% changed their morphology to "dead tree" termination; no subsequent changes were observed at either month 8 or month 12 (p < 0.0001 vs baseline). Fifty percent of eyes had a perilesional hypointense halo, which decreased to 25% at mes 4 (p = 0.0368) and remained stable until the end of follow-up; thus, this activity criterion disappeared in 50% of eyes at 12 months (p = 0.0368 vs baseline).</p><p id="par0070" class="elsevierStylePara elsevierViewall">All the lesions were active at the beginning of the study; however, by the fourth month only 15% of the lesions remained active, and this remained constant until the end of the study. The kappa interobserver match index was 0.97.</p><p id="par0075" class="elsevierStylePara elsevierViewall">As for BCVA, it improved 14.9 ± 7.7 letters in the fourth month (p < 0.0001), slightly but significantly decreased in the eighth month (1.1 ± 3.0 letters), and significantly improved 1.4 ± 2.2 letters in month 12. The overall improvement in BCVA at 12 months was 15.2 ± 3.3 letters (p < 0.0001 vs baseline) (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). Twenty-four patients (60%) gained at least 15 ETDRS letters at month 4 and 22 (55%) at month 8, remaining stable thereafter. There were no cases of VA loss.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">When analyzing the relationship between OCTA findings and visual outcomes, including all factors in the multivariate analysis, it was found that larger baseline area CNVs are independently associated with lower VA gain at 12 months; while larger baseline BCVA, larger baseline CMV and the presence of perilesional halo at the baseline visit are associated with greater visual gains. This model has been shown to explain 77% of the VA gain (R<span class="elsevierStyleSup">2</span> = 0.7512).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Our study reflects the usefulness of OCTA in the follow-up of <span class="elsevierStyleItalic">naïve</span> patients with CNV1 secondary to NAMD. We have observed improvements in BCVA associated with a reduction in CNV area and changes in several qualitative parameters of OCTA during the course of treatment with intravitreal aflibercept.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Evidence for the usefulness of OCTA in the follow-up of <span class="elsevierStyleItalic">naïve</span> patients with NAMD is scarce. Miere et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> reported a 65% reduction in lesion area after loading dose in <span class="elsevierStyleItalic">naïve</span> patients; however, the area increased in patients who had received previous treatment. These results suggest that lesion size can be considered as a marker of therapeutic response only in <span class="elsevierStyleItalic">naïve</span> patients.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Coscas et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> observed that the type of CNV can affect the degree of reduction in size; thus, in a patient with mixed CNV (type 1 and type 2) they found that the reduction of the type 1 component was less than that of the type 2 after anti-VEGF treatment. This could be explained by the greater difficulty of intravitreal therapy to reach lesions that are under the retinal pigment epithelium (RPE).</p><p id="par0100" class="elsevierStylePara elsevierViewall">The degree of lesion area reduction (50%, from 2.5 mm<span class="elsevierStyleSup">2</span> to 1.3 mm<span class="elsevierStyleSup">2</span>) observed in our patients after loading doses provides further scientific evidence for this parameter as a marker of therapeutic response in <span class="elsevierStyleItalic">naïve</span> patients presenting with CNV1 associated with NAMD. In addition, our study also demonstrates for the first time, to our knowledge, that the reduction in CNV area remains stable throughout the 12 months of follow-up with a fixed bimonthly regimen of intravitreal therapy with aflibercept.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Qualitative OCTA parameters indicated a reduction in the degree of CNV activity during the 12 months of treatment, with a significant decrease in the percentage of patients presenting thin capillaries (85%), anastomoses (70%), or perilesional hypointense halo (25%). In 90% of the eyes the peripheral arcuate terminal vessel morphology was replaced by a "dead tree" morphology, which is typical of mature angiogenic forms.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The morphology of the lesion (90% sea fan) remained unchanged during the study, which is compatible with the idea that the shape of the lesion may present independent patterns that do not go through sequential stages.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> According to the criteria of Coscas et al, after the loading dose 85% of CNVs became inactive, and this remained unchanged throughout the follow-up period.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The only study in which OCTA biomarkers have been evaluated during at least one year of follow-up did not include an exclusion criterion to turn away patients previously treated with antiangiogenic therapy.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The present study demonstrates the usefulness of OCTA in the diagnosis and follow-up of <span class="elsevierStyleItalic">naïve</span> patients treated with a fixed bimonthly regimen of aflibercept for one year. However, further studies are needed to analyze what happens when applying other treatment regimens, such as Treat and Extend or PRN.</p><p id="par0115" class="elsevierStylePara elsevierViewall">VA gain after the loading dose was 14.9 ± 7.7 letters and the gain at 12 months was 15.2 ± 3.3 letters. This gain exceeds the values reported in the VIEW 1 and 2 studies (7.9 ± 15.0 and 8.9 ± 14.4 letters, respectively)<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and those obtained in other daily clinical practice studies after 12 months of aflibercept treatment.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–16</span></a> In any case, comparison with other studies is not easy, since there are sociodemographic differences as well as differences related to the disease itself (baseline AVM; type of lesion; presence of hemorrhage, atrophy or fibrosis in the macular area among others).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In addition, it should be remembered that the present cohort of patients includes only those with CNV1, which is associated with greater VA gain.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> On the other hand, our health area is equipped with a powerful telemedicine network having the objective of detecting retinal pathologies at an early stage and improving the access of patients to specialized retinal consultations; this circumstance may also explain the fact that VA gain is higher despite being older patients, compared to the aforementioned studies.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The present study has some limitations. One is the small sample size; another is the manual segmentation, which may present a certain degree of subjectivity (although the degree of agreement between observers is very high), and the last one is that the flux density was not measured, which could have provided some additional information.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion, our study supports the usefulness of OCTA in the follow-up of <span class="elsevierStyleItalic">naïve</span> patients with NAMD with CNV1 who received fixed therapy with bimonthly intravitreal aflibercept for 1 year. Long-term studies are needed to assess the value of OCTA when other treatment regimens are adopted.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">No conflict of interest was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1838673" "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" => "xpalclavsec1602327" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1838674" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 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" => "xpalclavsec1602328" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-03" "fechaAceptado" => "2021-02-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1602327" "palabras" => array:5 [ 0 => "Age-related macular degeneration" 1 => "Choroidal neovascularisation" 2 => "OCT angiography" 3 => "anti-VEGF" 4 => "Aflibercept" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1602328" "palabras" => array:5 [ 0 => "Degeneración macular asociada a la edad" 1 => "Neovascularización coroidea" 2 => "OCT-angiografía" 3 => "Anti-VEGF" 4 => "Aflibercept" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">To assess the activity of biomarkers, through OCT angiography (OCTA), of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) treated with aflibercept. As secondary endpoints, visual acuity (VA) and the relationship between biomarkers and visual prognosis were also studied.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Prospective study that examined 33 eyes of 40 naïve patients with type 1 CNV secondary to AMD, who had been treated with aflibercept, according to summary of product characteristics, for one year. The patients were evaluated at the time of diagnosis, and at 4, 8 and 12 months.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The mean VA gain at 12 months was 15.2 ± 3.3 letters. The area of lesion decreased 1.2 ± 1.0 mm<span class="elsevierStyleSup">2</span> in the 4th month (<span class="elsevierStyleItalic">P</span> < .0001), remaining stable afterwards. The presence of tiny capillaries, anastomosis and perilesional hypointense halo was reduced by 85%, 70% and 25%, respectively, at 12 months of follow-up. The peripheral vascular arcade changed morphology, from having a leafy appearance to having a sharp appearance in 90% of cases. The size of the lesion and the presence/absence of perilesional hypointense halo were independently associated with the final VA, in such a way that larger lesions and the absence of a perilesional hypointense halo at the baseline visit were associated with less VA gain.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The OCTA is a useful, non-invasive tool that provides quantitative and qualitative information on the remodelling of the CNV vascular network after antiangiogenic therapy.</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">Objetivos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Evaluar la actividad de los biomarcadores, mediante OCT-angiografía (OCTA), en la neovascularización coroidea (NVC) secundaria a degeneración macular asociada a la edad (DMAE) tratada con aflibercept. Como objetivos secundarios se estudiaron la agudeza visual (AV) y la relación existente entre biomarcadores y pronóstico visual.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo en el que se estudiaron 33 ojos de 40 pacientes naïve diagnosticados de NVC tipo 1 secundaria a DMAE y que habían sido tratados con aflibercept, según ficha técnica, durante 1 año. Los pacientes fueron evaluados en el momento del diagnóstico, a los 4, a los 8 y a los 12 meses.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La ganancia media de AV a los 12 meses fue de 15,2 ± 3,3 letras. El área de lesión disminuyó 1,2 ± 1,0 mm<span class="elsevierStyleSup">2</span> en el cuarto mes (p < 0,0001), permaneciendo estable después. La presencia de capilares finos, anastomosis y halo hipointenso perilesional se redujo en el 85, el 70 y el 25%, respectivamente, a los 12 meses de seguimiento. La arcada vascular periférica cambió de morfología, pasando de tener un aspecto frondoso a tener un aspecto afilado en el 90% de los casos. El tamaño de la lesión y la presencia/ausencia de halo hipointenso perilesional se asociaron, de manera independiente, a la AV final, de tal forma que las lesiones de mayor tamaño y la ausencia de halo hipointenso perilesional en la visita basal se asociaron a menor ganancia de AV.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La OCTA se trata de una herramienta útil, no invasiva, que nos aporta información cuantitativa y cualitativa del remodelado de la red vascular de la NVC tras terapia antiangiogénica.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 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:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Campos Polo R, Gómez Sánchez I. Biomarcadores de OCT-angiografía en la neovascularización coroidea tipo 1 tras tratamiento con aflibercept durante 1 año. Arch Soc Esp Oftalmol. 2022;97:639–645.</p>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1200 "Ancho" => 2091 "Tamanyo" => 95731 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes in CMT (microns) during the study period. Mean baseline CMT: 447.08 ± 127.23. Mean CMT at month 4: 264.98 ± 93.53. Average CMT at month 8: 263,43 ± 98.76. Average CMT at month 12: 261.40 ± 103.27.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">p <  0.0001 vs. baseline; p = 0.5315 vs. month 4; p = 0.1381 vs. month 8.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1305 "Ancho" => 1305 "Tamanyo" => 184892 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Structural OCT and OCTA images of patient number 2. a) Structural OCT image from the baseline visit showing a CNV type 1 and adjacent subretinal fluid. b) OCTA image from the baseline visit showing a sea fan CNV, presence of small capillaries and anastomoses in the branches, peripheral terminating arcade in terminal vessel and hypointense perilesional halo (active CNV). c) Structural OCT image from month 12 visit where flattening of the pigment epithelium and disappearance of subretinal fluid is seen. d) OCT image from month 12 visit where small capillaries and branch anastomoses have disappeared, the terminal vessel has a "dead tree" appearance and perilesional hypointense halo persists (inactive CNV).</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1063 "Ancho" => 2175 "Tamanyo" => 73096 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Changes in mean CNV area (mm<span class="elsevierStyleSup">2</span>) during the study period. Mean area of the baseline CNV: 2,511.1 ± 1,901.2. Mean CNV area at month 4: 1,338.8 ± 1,093.77. Average area of the CNV at month 8: 1,332.7 ± 1,079.5. Average area of the NVC at month 12: 1,323.1 ± 1,075.9.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">* p < 0.0001 vs. baseline; † p = 0.5102 vs. month 4; § p = 0.0384 vs. month 8.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1305 "Ancho" => 1305 "Tamanyo" => 253414 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">OCTA images of patient number 13. a) Baseline stage: a well-defined sea fan shape, small capillaries in the branches, presence of anastomoses and peripheral terminal arcade in terminal vessel (active CNV). b) State of CNV after loading dose: mature vessels in the branches, absence of anastomoses and terminal vessel with a "dead tree" appearance (inactive CNV). c) CNV continues to be inactive at month 8. d) CNV inactive at month 12.</p>" ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1265 "Ancho" => 2167 "Tamanyo" => 92626 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Changes in mean BCVA (ETDRS letters) during the study period. Mean baseline BCVA: 29.05 ± 12.01. Mean BCVA at month 4: 43.93 ± 15.22. Mean BCVA at month 8: 42.80 ± 14.18. Average BCVA at month 12: 44.23 ± 14.60.</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">p < 0.0001 vs baseline; p = 0.0226 vs month 4; p = 0.0002 vs month 8.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "U. Schmidt-Erfurth" 1 => "V. Chong" 2 => "A. Loewenstein" 3 => "M. Larsen" 4 => "E. Souied" 5 => "R. 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