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Plasma rich in growth factors membrane as a macular hole treatment in a vitrectomized patient due to rhegmatogenous retinal detachment
Membrana de plasma rica en factores de crecimiento como tratamiento de agujero macular en una paciente vitrectomizada por desprendimiento de retina regmatógeno
C.M. Rangel Gualdróna,b,c, V. Galvis Ramírezd, J.D. Arias Aristizabald, M. Gómez Velascoa,c, K. Quintero Lizcanoa, A. Arias Gómeza,b,
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a Fundación Oftalmológica de Santander Carlos Ardila Lülle, Foscal, Bucaramanga, Santander, Colombia
b Centro Oftalmológico Virgilio Galvis, Bucaramanga, Santander, Colombia
c Universidad Autónoma de Bucaramanga (UNAB), Universidad Industrial de Santander (UIS), Bucaramanga, Santander, Colombia
d Clínica Foscal Internacional, Bucaramanga, Santander, Colombia
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A. OCT B-scan en la cual se observa cierre completo del agujero macular con atrofia de capas externas. B. Imagen a color de polo posterior del OD que muestra un agujero macular cerrado con migración de pigmento a región foveal. C. OCT angiografía de OD; se evidencia desaparición de los espacios pequeños hiporreflectivos que rodeaban el agujero macular en la capa nuclear interna y de las cavidades hiporreflectivas radiales alargadas que formaban un patrón estelar en el complejo de la plexiforme externa/capa de fibras de Henle. D. Imagen en-face OD sin evidencia de DONFL.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C.M. Rangel Gualdrón, V. Galvis Ramírez, J.D. Arias Aristizabal, M. Gómez Velasco, K. Quintero Lizcano, A. Arias Gómez" "autores" => array:6 [ 0 => array:2 [ "nombre" => "C.M." "apellidos" => "Rangel Gualdrón" ] 1 => array:2 [ "nombre" => "V." "apellidos" => "Galvis Ramírez" ] 2 => array:2 [ "nombre" => "J.D." 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"apellidos" => "Arias Gómez" "email" => array:1 [ 0 => "dr.alejandroariasgomez@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Fundación Oftalmológica de Santander Carlos Ardila Lülle, Foscal, Bucaramanga, Santander, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro Oftalmológico Virgilio Galvis, Bucaramanga, Santander, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Universidad Autónoma de Bucaramanga (UNAB), Universidad Industrial de Santander (UIS), Bucaramanga, Santander, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Clínica Foscal Internacional, Bucaramanga, Santander, Colombia" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Membrana de plasma rica en factores de crecimiento como tratamiento de agujero macular en una paciente vitrectomizada por desprendimiento de retina regmatógeno" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2895 "Ancho" => 3258 "Tamanyo" => 1167194 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Multimodal image of the right eye. A. OCT B-scan showing complete closure of the macular foramen with atrophy of the outer layers. B. Colour image of posterior pole of the RE showing a closed macular hole with pigment migration to the foveal region. C. OCT angiography of the RE, showing disappearance of the small hyporeflective spaces surrounding the macular hole in the inner nuclear layer and the elongated radial hyporeflective cavities that formed a stellate pattern in the outer plexiform/Henle’s fibre layer complex. C. RE en-face image.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Macular hole (MH) formation after vitrectomy is a rare complication. The pathophysiological mechanisms are not clear and are probably different from those involved in idiopathic MH formation since in vitrectomised eyes posterior vitreous detachment (PVD) and its removal eliminates these mechanisms.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> Published series describe the treatment in these cases as peeling of the internal limiting membrane (ILM) with the use of long-acting tamponades with closure rates between 50 and 100% of cases. It is known that rhegmatogenous retinal detachment (RRD) with macula-off is the factor associated with the highest number of surgeries required to achieve closure of the ILM.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The case of a patient with a history of DRR with macula-off is reported. The patient presented with AM in the late postoperative period and was treated with plasma membrane rich in growth factors (PRGF) without ILM removal, presenting closure of the MH without recurrence at twelve months follow-up. This is a relatively new technique with promising results that can be used as a treatment for complex MH.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 54-year-old woman consulted for decreased vision in her right eye (RE) with a 1 week evolution. The initial vision was hand movement, the anterior segment evidenced a lens with NO2NC2C2 and in the fundus there was a DRR with macula-off and a peripheral tear in meridian 1. In the left eye (LE) vision was 20/25 with a normal ophthalmological examination.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The lens was removed by phacoemulsification with intraocular lens implantation, pars plana vitrectomy (PPV), while the tear was surrounded with laser and sulphur hexafluoride (SF6) was used as a tamponade. One year after surgery the best corrected vision in RE was 20/200 and four years later the patient consulted again for decreased vision in the same eye. Finger-count vision, fundus MH and a treated peripheral tear were found. Optical coherence tomography (OCT) showed an MH with an aperture diameter of 905 µm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">PPV was performed using PRGF membrane on the MH without ILM removal as treatment. For the preparation of the PRGF membrane, blood samples were obtained in tubes with sodium citrate as anticoagulant and processed according to the PRGF-Endoret protocol. Each tube was centrifuged for 8 min at 580 g and different fractions were obtained: F1 with a platelet concentration similar to peripheral blood, F2 with two to three times the platelet concentration of peripheral blood and F3 corresponding to whole blood, 2 ml of F2 was obtained to prepare leukocyte-free PRGF. To achieve the three-dimensional structure, the sample was activated with 10% CaCl<span class="elsevierStyleInf">2</span> and incubated at 37 °C until clotted. The clot was placed in a forming vessel and pressure was applied for 30 s to obtain a 100 µm thick PRGF membrane.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In the surgical procedure we used 23-G trocars placed 3.5 mm from the limbus to make a fluid–air exchange, supernatant of the obtained plasma was placed over the macula for 6 min, then it was aspirated and the PRGF membrane segment was placed inside the MH with ILM forceps, then silicone oil (AS) was injected as a buffer. Two months after surgery, vision was 20/800 and OCT showed the PRGF membrane integrated over the MH (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). At six months postoperative OCT showed a closed MH with a visual acuity of 20/600, AS removal was performed and twelve months after surgery with PRGF membrane there was no evidence of MH recurrence (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) with a vision of 20/200 (−1.00 to 2.25 × 0).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">MH is a retinal tear located in the centre of the fovea that produces central scotoma and visual loss. Based on clinical and OCT imaging data it has been confirmed that interactions between various forces in the fovea, mainly anteroposterior and tangential traction exerted by the vitreous, are the main pathophysiological mechanism.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> The techniques used in MH surgery aim to eliminate these forces by inducing PVD with the removal of the posterior cortical vitreous and to cancel the traction forces exerted by the superficial membranes (epiretinal membranes (ERM) and ILM) by removing them.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The formation of an MH following vitrectomy is rare with an incidence of 0.24%–1.9%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Recent studies have suggested that the presence of ERM, high myopia, macular edema and iatrogenic factors may contribute to MH formation within 3 months after vitrectomy. Medina et al. found possible associations such as the presence of ERM (73% of eyes), DRR with macula-off (60%), recurrent DRR (47%) and high myopia (56%).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Cunningham et al. reported an incidence of MH following vitrectomy of 0.8%, identifying ERM prior to MH repair in 50% of eyes and macula-off DRR in 100% of cases.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Khurana et al. analysed 14 cases of post vitrectomy MH for DRR, 43% of cases had macula-off at diagnosis and a ERM in 100% of cases prior to surgery to treat the MH.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> Kang et al. found an incidence of secondary MH of 0.6%; prior to the formation of these macular holes a ERM was the most common OCT feature (50%) and a higher proportion of eyes with MH had high myopia (32% ≥26 mm vs. 5% of eyes ≤22 mm).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Residual cortical vitreous with posterior shrinkage or incomplete PVD secondary to vitreoschisis during vitrectomy remain possible factors associated with these MAs.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The formation of a ERM with the resulting tangential traction is an explanation for most cases of MH following DRR repair, however, in the absence of a ERM as in the case we report it is likely that ILM is involved. The use of lasers on the peripheral retina and shrinkage of the vitreous base despite good vitreous base shaving may result in intrinsic tangential traction of the ILM.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Nakanishi et al. analysed OCT images of the detached macula in DRR and described loss of photoreceptor inner and outer segments in the fovea in 40% of eyes and diffuse oedema in the outer nuclear layer in 67% of cases. This effect may weaken the outer retinal layers facilitating the formation of an MH with minimal tangential traction.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Post-vitrectomy anatomical outcomes for closure of these MH tend to be good, however, Kang et al. found that 28% of eyes with macular holes after vitrectomy required multiple surgeries for closure. They suggest that improving the success of a single surgery may require greater caution in eyes with large MH, preoperative ERM and a history of DRR with macula-off, although only the latter clinical factor was significant in multivariate analysis. In such cases, techniques such as ILM transplantation, injection of plasma rich in growth factors, longer mechanical pressure with silicone oil or heavy silicone oil injection and traction relief by complete ILM peeling should be considered.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Visual outcomes following MH closure are variable and in most cases improvement in visual acuity has been reported.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> OCT images showing subfoveal disruption of the ellipsoid area may predict worse outcomes.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Considering that the MH of the present patient was large and that she had a history of DRR with macula-off, it was decided to use PRGF membrane given the risk of recurrence without evidence of recurrence one year after surgery and with visual improvement. It is important to mention that when using PRGF membrane in our patients we did not routinely perform ILM peeling with high MH closure rates.</p><p id="par0070" class="elsevierStylePara elsevierViewall">PRGF membrane has mechanical properties and strengths that allow it to be used in surgical procedures. It has been shown to contain growth factors that are released in a progressive and sustained manner and serve as a scaffold for cell regeneration. The mechanism related to the closure of the MH is given by the trophic action of growth factors such as PDGF, b-FGF and EGF and by the activation of Muller cells.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This technique has been used in the management of complex MHs with excellent anatomical and functional results in the short and long term as in the case of recurrent MHs.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> recurrent myopic MHs<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and secondary to diseases such as macular telangiectasia type 2 where they are an infrequent complication.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">We report this case as macular holes in long-term vitrectomised eyes are rare. In addition, we use a novel technique that is likely to reduce the risk of recurrence, which may have been high given the risk factors presented by the patient.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Source of funding</span><p id="par0080" class="elsevierStylePara elsevierViewall">Not applicable. There was no source of funding for this article.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">No conflicts of interest were declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1897949" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1642079" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1897948" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1642078" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Source of funding" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-11-20" "fechaAceptado" => "2023-03-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1642079" "palabras" => array:4 [ 0 => "Plasma rich in growth factors membrane" 1 => "Macular hole" 2 => "Rhegmatogenous retinal detachment" 3 => "Vitrectomy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1642078" "palabras" => array:4 [ 0 => "Membrana de plasma rica en factores de crecimiento" 1 => "Agujero macular" 2 => "Desprendimiento de retina regmatógeno" 3 => "Vitrectomía" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The formation of a macular hole after vitrectomy due to rhegmatogenous retinal detachment is a rare complication. Although there are different surgical options in the treatment of these macular holes with favorable outcomes, it has been shown that the history of macula-off retinal detachment is the most important risk factor related to the need for multiple interventions to close these macular holes, therefore special attention should be paid in the management of these patients.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">We present the case of a patient with macula-off rhegmatogenous retinal detachment who required treatment with cataract surgery with intraocular lens implant and pars plana vitrectomy. Four years after the primary surgery, she presented a large macular hole, and was treated with membrane of plasm rich in growth factors with closure of the macular hole and visual improvement without recurrence 12 months after surgery.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La formación de un agujero macular tras una vitrectomía por desprendimiento de retina regmatógeno es una complicación rara. Aunque existen diferentes opciones quirúrgicas en el tratamiento de estos agujeros maculares con buenos resultados, se ha demostrado que el antecedente de un desprendimiento de retina con compromiso macular es el factor de riesgo más importante relacionado con la necesidad de múltiples intervenciones para el cierre de estos agujeros, por lo que debe prestarse especial atención al manejo de estos pacientes.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Presentamos el caso de una paciente con desprendimiento de retina regmatógeno con compromiso macular que requirió tratamiento con cirugía de catarata, implante de lente intraocular y vitrectomía vía pars plana. Cuatro años después de la cirugía primaria presentó un agujero macular grande y fue tratada con membrana de plasma rica en factores de crecimiento con cierre del agujero macular y mejoría visual sin recidiva 12 meses después de la cirugía.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rangel Gualdrón CM, Galvis Ramírez V, Arias Aristizabal JD, Gómez Velasco M, Quintero Lizcano K, Arias Gómez A. Membrana de plasma rica en factores de crecimiento como tratamiento de agujero macular en una paciente vitrectomizada por desprendimiento de retina regmatógeno. Arch Soc Esp Oftalmol. 2023. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.oftal.2023.03.009">https://doi.org/10.1016/j.oftal.2023.03.009</span></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" => 2968 "Ancho" => 3258 "Tamanyo" => 1107871 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Multimodal image of the right eye. A. OCT B-scan showing full-thickness macular hole with a basal diameter of 1270 µm, minimum linear dimension of 749 µm, internal aperture of 905 µm, macular hole height of 558 µm. B. Colour image of the posterior pole of the RE showing the macular hole. C. OCT angiography of the RE, showing small hyporeflective spaces surrounding the macular hole in the inner nuclear layer and elongated radial hyporeflective cavities forming a stellate pattern in the outer plexiform/Henle’s fibre layer complex. C. RE en-face image, showing the hyporeflective spaces in the inner nuclear layer and in the outer plexiform/Henle’s fibre layer complex.</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" => 1777 "Ancho" => 3258 "Tamanyo" => 499617 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Post-operative OCT B-scan. A. Day 5 post-op, PRGF membrane positioned within the MH. B. 2 months postoperative, complete closure of the macular hole is observed.</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" => 2895 "Ancho" => 3258 "Tamanyo" => 1167194 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Multimodal image of the right eye. A. OCT B-scan showing complete closure of the macular foramen with atrophy of the outer layers. B. Colour image of posterior pole of the RE showing a closed macular hole with pigment migration to the foveal region. C. OCT angiography of the RE, showing disappearance of the small hyporeflective spaces surrounding the macular hole in the inner nuclear layer and the elongated radial hyporeflective cavities that formed a stellate pattern in the outer plexiform/Henle’s fibre layer complex. C. RE en-face image.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical characteristics, risk factors, and surgical outcomes of secondary macular hole after vitrectomy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.G. Kang" 1 => "J.Y. Han" 2 => "E.Y. Choi" 3 => "S.H. Byeon" 4 => "S.S. Kim" 5 => "H.J. 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