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Vitrectomy with subretinal tissue plasminogen activator (r-TPA) and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) for submacular hemorrhages treatment: Retrospective analysis of 22 cases
Vitrectomía asociada a activador tisular del plasminógeno (rTPA) subretiniano e inyección intravítrea de anti-VEGF como tratamiento de hemorragias submaculares: análisis retrospectivo de 22 casos
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Herranz Cabarcos, M.J. Quiroz Quiroga, I. Alarcón Valero, M. Castilla Martí, V. Pospoki, D. Vilaplana Blanch" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Herranz Cabarcos" "email" => array:1 [ 0 => "alejandra.herranz.cabarcos@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.J." "apellidos" => "Quiroz Quiroga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Alarcón Valero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M." 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"apellidos" => "Vilaplana Blanch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Oftalmología, Consorci Sanitari Moisès Broggi, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Oftalmología, Hospital de l’Esperança - Parc de Salut Mar, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vitrectomía asociada a activador tisular del plasminógeno (rTPA) subretiniano e inyección intravítrea de anti-VEGF como tratamiento de hemorragias submaculares: análisis retrospectivo de 22 casos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2481 "Ancho" => 1504 "Tamanyo" => 314509 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Preoperative study of macular hemorrhage: retinography using ImageJ® software and OCT image.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Macular subretinal hemorrhages or hematomas are defined as the accumulation of blood between the neurosensory retina and the pigment epithelium, larger than one papillary diameter<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>, constituting a complication of retinal pathologies such as age-related macular degeneration (AMD) or macroaneurysms. In most cases, their appearance leads to a worsening of the visual prognosis of patients<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. The therapeutic approach to macular hemorrhages is not standardised and may be limited to observation or include invasive measures such as treatment with intravitreal anti-VEGF therapy or surgery.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Current hypotheses to explain the damage to vision caused by these hemorrhages are based on the toxicity of the iron released by the hemoglobin in the subretinal space and on the barrier effect of the hemorrhage itself, which would limit metabolic transport by diffusion between retinal layers, a basic condition for maintaining homeostasis.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The prevention of retinal damage to the retina caused by macular hemorrhages through these two pathophysiological pathways is the basis of the surgical treatment proposed so far.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 1996, Heriot et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> proposed surgical treatment of macular hemorrhages by mechanical displacement of the blood, using an expandable gas such as sulphur hexafluoride (SF<span class="elsevierStyleInf">6</span>) or octafluoropropane (<span class="elsevierStyleInf">3</span>CF<span class="elsevierStyleInf">8</span>). The improvement in visual acuity (VA) in treated patients was modest, from approximately 0.02 preoperatively to 0.06 after surgery.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In 2000. Hesse et al. proposed to associate intravitreal instillation of expandable gas with the administration, also in the vitreous cavity, of tissue plasminogen activator (rTPA)<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>. The results indicate an improvement in VA of approximately 0.03 to 0.1 after the procedure, associated with almost complete liquefaction of the hemorrhages within three days of bleeding.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The high molecular weight of rTPA and the low permeability of the inner retinal layers to this type of substance have led to extensive discussion about the actual effect of the drug at the subretinal level when administered in the vitreous cavity<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>. For this reason, and given the safety profile of the fibrinolytic, its application directly into the subretinal space<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>, associated with intravitreal anti-VEGF therapy, was proposed.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The work published in 2010 by Arias et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> using vitrectomy associated with subretinal rTPA, intravitreal anti-VEGF and expandable gas demonstrated an improvement in visual acuity in 93% of treated patients of 2 ETDRS lines or more.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The aim of this retrospective study is to analyse the effectiveness of treatment of macular subretinal hemorrhages by vitrectomy, intravitreal injection of expandable gas (SF/<span class="elsevierStyleInf">63</span> CF<span class="elsevierStyleInf">8</span>) and anti-VEGF drugs (aflibercept/ranibizumab) associated with subretinal infiltration of rTPA, based on our experience over the last five years.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">A retrospective analysis of macular hemorrhage cases, operated by 23G pars plana vitrectomy associated with infiltration of subretinal rTPA and expandable gas in the same centre (H. de la Esperança - Parc de Salut Mar, Barcelona, Spain) by multiple surgeons over a period of five years, from the implementation of the technique to the present time, was carried out.</p><p id="par0050" class="elsevierStylePara elsevierViewall">All research methods applied in this study comply with the Declaration of Helsinki. The present study has been approved by the Ethics Committee of Parc de Salut Mar, Barcelona, Spain. All included patients signed an informed consent form before participating in the study.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Anamnesis data collected preoperatively include age, gender, systemic comorbidities – including diabetes mellitus, dyslipidemia, hypertension and treatment with antiplatelet or anticoagulant drugs –, ophthalmological comorbidities and the period measured in days from the onset of visual symptoms to the execution of the surgical procedure.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Ophthalmological physical examination data collected preoperatively in the analysis included: VA measured by ETDRS score, retinography, macular optical coherence tomography (OCT), anterior segment examination by biomicroscopy and intraocular pressure measured by Goldmann tonometry. A measurement of the size of the hemorrhages was performed on retinograms obtained using the free collaborative software ImageJ® (developed by Wayne Rasband for the <span class="elsevierStyleItalic">National Institute of Health</span>, USA). For image calibration, in order to avoid the impact of refractive defects on the measurement, the inferior temporal vein (ITV) at the exit of the optic disc, with a known and stable diameter of 125 um<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>, was used as a reference (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The surgical technique applied in these patients included complete vitrectomy via 23G pars plana (Constellation Vision System, Alcon, Forth Worth, TX, USA; Facovitrectome EVA, DORC, Zuidland, The Netherlands); subsequently instilling rTPA into the subretinal space, which is accessed using a 23G cannula with a 41G retractable tip. The volume of rTPA used should be sufficient to induce a localised retinal detachment, encompassing at least the area of macular involvement of the hemorrhage. This is followed by an exchange with air and 20% sulphur hexafluoride (SF<span class="elsevierStyleInf">6</span>) to achieve pneumatic displacement of the hemorrhage. Finally, the drug with anti-VEGF activity is injected intravitreally. In all patients, a period of postoperative rest in prone position for seven days is recommended.</p><p id="par0070" class="elsevierStylePara elsevierViewall">During postoperative follow-up, data on VA evolution and development of complications were collected for a minimum period of six months.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">Continuous quantitative variables are described by mean and standard deviation (SD). Qualitative variables are described by frequency tables (number and percentage). Patients were divided into two groups according to their postoperative ETDRS score: less than or equal to 35 and greater than 35. For comparison of continuous quantitative variables, the Mann–Whitney U-test was applied. For qualitative variables, the Chi-square or Fisher's exact test was used. Differences between preoperative and postoperative VA, both at 3 months and at the end of patient follow-up, were analysed using the Wilcoxon matched-pairs test.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using STATA 15.1 software (STATA Corp. LLC, Texas, USA). The results were considered statistically significant at a p-value < 0.05.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0085" class="elsevierStylePara elsevierViewall">Twenty-two eyes of 22 patients were included in the study, with an average age at diagnosis of 84.4 years (SD: 6.99 years), of whom 12 were female (52.2%). The systemic and ophthalmological comorbidities found in the anamnesis are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The most prevalent of the systemic comorbidities was arterial hypertension in 17 cases (77.17%). Ophthalmologically, 15 patients (63.62%) had a history of AMD; in five cases (22.72%), prior intravitreal treatment with anti-VEGF was required. No comorbidity, including treatment with antiplatelet or anticoagulant drugs, showed a positive association. There was also no statistically significant relationship between the area of hemorrhage and these treatments.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">With regard to the size of the macular hemorrhages, in three patients (13.63%), hemorrhages known as massive hemorrhages were observed in the preoperative retinographs, as they reached at least one of the temporal vascular arcades.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Surgical intervention was performed on average 13.95 days (SD: 13.49 days) after the onset of visual symptoms. In 16 of the 22 patients, the procedure was performed less than 14 days after the onset of symptoms associated with hemorrhage. In one of the treated cases, the period from clinical onset to surgical treatment of the hemorrhage was 120 days, as the patient developed adenoviral conjunctivitis.</p><p id="par0100" class="elsevierStylePara elsevierViewall">No intraoperative complications were reported. In 19 cases (86.3%) the etiological diagnosis was exudative AMD; in the remaining three cases (13.63%) the macular hemorrhage was a consequence of active bleeding from a retinal macroaneurysm.</p><p id="par0105" class="elsevierStylePara elsevierViewall">In 16 patients (72.72%) an improvement in VA was observed three months after the surgical intervention, this difference being statistically significant (p = 0.011). Two of the three patients in the study sample who had massive hemorrhages were included in this group, improving one line of vision according to the ETDRS scale in one case and two lines of vision in the other. In 15 patients (68.18%) this improvement was maintained at six months, including the two patients with massive hemorrhage.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In two patients (9.09%), no change in postoperative VA compared to preoperative VA was observed. In four patients (18.2%) who underwent surgery, visual acuity three months after the operation was worse than before the procedure.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The characteristics of the hemorrhages in terms of etiology, time between the onset of symptoms and surgery, and pre- and postoperative visual acuity are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Statistical analysis did not show any relationship between the etiology of macular hemorrhage and visual prognosis. There was also no statistical relationship between the size of the hemorrhages and postoperative visual prognosis.</p><p id="par0125" class="elsevierStylePara elsevierViewall">There was no statistically significant relationship between time from symptom onset to surgery and postoperative visual acuity.</p><p id="par0130" class="elsevierStylePara elsevierViewall">During the immediate postoperative follow-up, three patients developed hemovitreousl, in two cases accompanied by hyphema, and three patients developed ocular hypertension. The average follow-up of the patients after surgery was 23.5 months. During this period, 12 of them required intravitreal treatment with anti-VEGF drugs.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0135" class="elsevierStylePara elsevierViewall">Treatment of macular hemorrhages by vitrectomy combined with subretinal tissue plasminogen inhibitor, expandable gas and anti-VEGF therapy has been shown on numerous occasions to improve the visual prognosis of affected patients compared to those who receive no treatment<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8,10,11</span></a>. Analysis of the data obtained in the present study confirms these results.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In the study published by González López et al. in 2016<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>, it was observed that the shorter time interval between the onset of symptoms and the surgical procedure is a prognostic factor to be taken into account.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In the present case, although the results point to better final visual acuity in patients who were operated on earlier, the relationship was not statistically significant, probably due to the small sample size. It should also be noted that in our group of patients a postoperative VA improvement of 8 and 21 points on the ETDRS scale was observed in two patients in whom 44 and 45 days had elapsed between the onset of visual symptoms and the intervention.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In the same series published by González et al<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>, a statistically significant positive relationship between smaller hemorrhage size and better visual prognosis is reported. It was not possible to confirm this relationship in the present study, probably due to the small size of the population sample. Despite this, it should be taken into account that, unlike most of the literature references consulted, in our case we did not rule out surgical treatment for patients affected by this type of hemorrhage, nor did we exclude them from the statistical analysis. Thus, it was observed that two of the three patients with large hemorrhages, reaching at least one of the temporal retinal vascular arcades, showed sustained improvement in visual acuity over time.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Based on the above two points, we believe that even in patients with long-standing or large macular hemorrhages, the surgical approach may be a viable therapeutic option.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Regarding the comorbidities presented by the affected patients, the observed prevalence of 77% of systemic arterial hypertension is consistent with the demographic data published in previous series for macular hemorrhages associated with macroaneurysms. The series published by Robertson et al. and Rabb et al. indicate prevalences of 75%<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> of macular hemorrhages in these cases. The association between AMD and hypertension has been demonstrated in numerous studies with various levels of evidence<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>, but we have found no published data on the risk of macular hemorrhages in patients with AMD and hypertension. Although the observed relationship between the two factors is not statistically significant, the data suggest that patients with exudative AMD may benefit from antihypertensive therapy, reducing the risk of developing macular hemorrhages.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Although we initially considered that the etiology of the hemorrhages could be a prognostic factor, based on the fact that retinal structural alterations would be more advanced in patients with AMD, a statistically significant relationship between etiology of the hemorrhage and postoperative VA was not observed.</p><p id="par0170" class="elsevierStylePara elsevierViewall">The present study has several limitations, the most notable of which are its retrospective nature, the absence of a control group and the small sample size.</p><p id="par0175" class="elsevierStylePara elsevierViewall">We would like to highlight the usefulness of the ImageJ® software for the standardised measurement of intraocular lesions. Its application has also been described for the measurement of extraocular lesions on reference images. The free and intuitive nature of this software makes it a tool to be taken into account both in clinical practice and research.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">No conflicts of interests were declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1740879" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1535379" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1740880" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1535380" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-04-27" "fechaAceptado" => "2021-07-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1535379" "palabras" => array:6 [ 0 => "Macular hemorrhage" 1 => "Subretinal hemorrhage" 2 => "Macroaneurysm" 3 => "Exudative age related macular degeneration" 4 => "Subretinal rTPA" 5 => "ImageJ" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1535380" "palabras" => array:6 [ 0 => "Hemorragia macular" 1 => "Hemorragia subretiniana" 2 => "Macroaneurisma" 3 => "Degeneración macular asociada a la edad exudativa" 4 => "rTPA subretiniano" 5 => "ImageJ" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Macular hemorrhages are a severe complication of other retinal pathologies, such as age-related macular degeneration (AMD) or macroaneurysms. Their therapeutic approach is not standardized, and can vary from observation to surgical treatment.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Retrospective analysis of 22 cases of macular hemorrhage, treated with vitrectomy associated to subretinal rTPA and intravitreal anti-VEGF over a period of 5 years.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">22 eyes of 22 patients were included, of which 12 (52%) were women. The mean age at diagnosis was 84.4 years. 13 patients were pseudophakic (54.1%) and 19 (86.36%) had previous ophthalmological comorbidities. The etiology of the macular hemorrhage was AMD in 19 patients (86.36%). The mean of best VA corrected at diagnosis was 24.55 (Early Treatment Diabetic Retinopathy Study score -ETDRS), with a statistically significant improvement to 36.78 3 months after surgery (p = 0.011). With an average of 23.5 months of follow-up, no differences in prognosis associated with the etiology or size of the hemorrhage were observed.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The treatment of macular hemorrhages by vitrectomy, subretinal rTPA and antiVEGF improves the visual prognosis of affected patients.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Las hemorragias maculares suponen una complicación severa de otras patologías retinianas, como la degeneración macular asociada a la edad (DMAE) o los macroaneurismas. El abordaje terapéutico de las mismas no se encuentra estandarizado, pudiendo variar desde la observación hasta el tratamiento quirúrgico.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Análisis retrospectivo de 22 casos de hemorragia macular, tratados mediante vitrectomías asociada a rTPA subretiniano y antiVEGF intravítreo durante un período de cinco años.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 22 ojos de 22 pacientes, de los que 12 (52%) eran mujeres. La edad media al diagnóstico fue de 84,4 años. Del total de pacientes, 13 eran pseudofáquicos (54,1%) y 19 (86,36%) presentaban comorbilidades oftalmológicas previas. La etiología de las hemorragias maculares fue DMAE en 19 pacientes (86,36%). La media de mejor agudeza visual (AV) corregida al diagnóstico fue de 24,55 (puntuación Early Treatment Diabetic Retinopathy Study - ETDRS), con una mejoría estadísticamente significativa a 36,78 a los tres meses de la cirugía (p = 0,011). Con un promedio de 23,5 meses de seguimiento, no se observaron diferencias en el pronóstico asociadas a etiología o tamaño de la hemorragia.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El tratamiento de las hemorragias maculares mediante vitrectomía, rTPA subretiniano y antiVEGF mejora el pronóstico visual de los pacientes afectos.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Herranz Cabarcos A, Quiroz Quiroga MJ, Alarcón Valero I, Castilla Martí M, Pospoki V, Vilaplana Blanch D. Vitrectomía asociada a activador tisular del plasminógeno (rTPA) subretiniano e inyección intravítrea de anti-VEGF como tratamiento de hemorragias submaculares: análisis retrospectivo de 22 casos. Arch Soc Esp Oftalmol. 2022;97:391–395.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2481 "Ancho" => 1504 "Tamanyo" => 314509 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Preoperative study of macular hemorrhage: retinography using ImageJ® software and OCT image.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">AMD: age-related macular degeneration; DM: diabetes mellitus; HT: hypertension; SD: standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age, years (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84.4 (6.99) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Gender (women, %)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (52.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Systemic comorbidities (n,%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HTA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (77.27%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (22.72%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Treatment with anticoagulants/anti-aggregants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (52.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Pre-operative ophthalmological comorbidities</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dry AMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (40.90%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Exudative AMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (22.72%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glaucoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (18.18%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Central retinal vein obstruction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4.54%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Pre-operative characteristics of the sample.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AMD: age-related macular degeneration; SD: standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Etiology</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DMAE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Macroaneurysm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Days between onset of clinic and surgical treatment</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Average (days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.57 (FROM: 25.74) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Medium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9,0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Minimum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Maximum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">ETDRS score (average)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>To diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.55 FROM 20.99 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>After 3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.78 DE 23.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; 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