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Radiation maculopathy treated with intravitreal bevacizumab
Bevacizumab intravítreo en el tratamiento de la maculopatía por radiación
J.L. Sánchez-Vicente, A. Muñoz-Morales, M.P. Galván-Carrasco
, A. Castilla-Lázpita, C. Vital-Berral, A. Alfaro-Juárez, T. Rueda-Rueda
Corresponding author
Unidad de Gestión Clínica de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
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Sánchez-Vicente, A. Muñoz-Morales, M.P. Galván-Carrasco, A. Castilla-Lázpita, C. Vital-Berral, A. Alfaro-Juárez, T. Rueda-Rueda" "autores" => array:7 [ 0 => array:2 [ "nombre" => "J.L." "apellidos" => "Sánchez-Vicente" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Muñoz-Morales" ] 2 => array:4 [ "nombre" => "M.P." "apellidos" => "Galván-Carrasco" "email" => array:1 [ 0 => "mpazgalvan@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Castilla-Lázpita" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Vital-Berral" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Alfaro-Juárez" ] 6 => array:2 [ "nombre" => "T." "apellidos" => "Rueda-Rueda" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Gestión Clínica de Oftalmología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Bevacizumab intravítreo en el tratamiento de la maculopatía por radiación" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig5" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1159 "Ancho" => 2833 "Tamanyo" => 612686 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">OCT after 3 bevacizumab injections. Foveal profile recovery and disappearance of juxtafoveolar cysts.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Radiation retinopathy (RR) is a slow progressing occlusive retinal microangiopathy that appears as a consequence of exposure to radiation during the treatment of ocular, orbital and cranial tumors and inflammatory diseases.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> It constitutes the most frequent cause of severe vision loss after radiotherapy for choroidal melanoma.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> The most frequent earliest clinical expression of RR is the presence of macular edema. Subsequent ophthalmoscopic findings include areas without capillary perfusion, microaneurysms, retinal hemorrhages, intraretinal exudates, nerve fiber layer infarcts, perivascular sheathing and retinal and optic disc neovascularization.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The case of a patient with radiation maculopathy after treatment of choroidal melanoma that responded positively to bevacizumab is presented.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinic case report</span><p id="par0015" class="elsevierStylePara elsevierViewall">Female, 47, who attended a routine checkup. The patient had been treated abroad 5 years ago for a choroidal melanoma in the left eye (LE) with plaque brachytherapy. Subsequently she had undergone cataract operation in the same eye with phacoemulsification and intraocular lens implant. Maximum corrected visual acuity (MCVA) of 1.0 in the right eye and 0.63 in the LE. Anterior segment exploration was normal, as well as intraocular pressure. Ocular fundus exhibited a flat cicatricial lesion in the temporal retina extending from II to IV, corresponding to the treated melanoma. The lesion was surrounded by a laser barrier. Temporally from the macula hard exudates and hemorrhages could be observed. The macula included hemorrhages and telangiectasia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Fluorescein angiography was carried out. In early times hemorrhages, telangiectasiae, microaneurysms and ischemia areas could be observed in the macular area (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The median periphery exhibited hemorrhages, microaneurysms and telangiectasiae. Late stages showed generalized diffusion with macular edema (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Optical coherence tomography (OCT) (Topcon® 3 D OCT-1000. Topcon Corporation, Tokio, Japan) showed the presence of a large cyst nasally from the fovea (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">On the basis of the clinical records and the data obtained in said explorations, the diagnostic of radiation maculopathy was reached and treatment was established with 3 intravitreal injections of bevacizumab at 4 week intervals. After treatment, the macular edema resolved and exudation in the area temporally from the macula diminished (<a class="elsevierStyleCrossRef" href="#fig5">Fig. 5</a>), improving visual acuity (VA) up to 1.0. The patient was followed up during 2 years without exhibiting macular edema recurrences.</p><elsevierMultimedia ident="fig5"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">Radiation maculopathy constitutes an important cause of VA loss after radiotherapy treatment in choroidal melanoma plaques. It involves 70% of cases where the total dose affecting the fovea is above 75<span class="elsevierStyleHsp" style=""></span>Gy. It usually presents between 6 months and 5 years after treatment. The literature describes cases that appeared between one month and 20 years after therapy. Radiation maculopathy presents as a consequence of endothelial cell loss of the perifoveal capillaries that lead to vascular occlusion, with dilatation of collateral capillary channels and formation of microaneurysms.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The vascular endothelial growth factor (VEGF) has been involved in the pathogenesis of radiation maculopathy. For this reason, antiangiogenics medicaments that inhibit VEGF production have been utilized by multiple authors for treating said condition albeit with variable results according to patient age, duration of maculopathy, type of plaque, applied regime, etc.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a>.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Even though the efficacy of bevacizumab has been demonstrated in small case series, to date there are no large series of clinical trials evaluating the use of said medicament in radiation maculopathy.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The patient of the described case had visited the authors’ hospital for a routine checkup after treatment carried out in another country. She did not refer recent VA alterations and therefore it was not possible to define the exact moment of onset or its duration. Treatment with bevacizumab proved to be effective as the macular edema disappeared and VA improved. No relapses occurred during the follow-up. The fact that the patient was relatively young (42 at treatment) and had no associated cardiovascular diseases could have influenced the positive response to treatment.</p><p id="par0055" class="elsevierStylePara elsevierViewall">However, better results could be obtained in prevention, either improving treatment protocols or avoiding excessive dosages and applying adequate fractions. On the other hand, even though some papers have recommended the preventive use of anti-VEGF,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">8,9</span></a> due to the absence of a predictable time window between exposure to radiotherapy and onset of the condition, the current trend is to use antiangiogenics in the emergence of incipient signs.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres845227" "titulo" => "Abstract" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Case report" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec840108" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres845226" "titulo" => "Resumen" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Caso clínico" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec840109" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinic case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-12" "fechaAceptado" => "2016-10-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec840108" "palabras" => array:5 [ 0 => "Radiation maculopathy" 1 => "Radiation retinopathy" 2 => "Choroidal melanoma" 3 => "Bevacizumab" 4 => "Macular edema" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec840109" "palabras" => array:5 [ 0 => "Maculopatía por radiación" 1 => "Retinopatía por radiación" 2 => "Melanoma coroideo" 3 => "Bevacizumab" 4 => "Edema macular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case report</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A 47 year-old woman with a choroidal melanoma developed a macular edema secondary to radiation therapy 75 months after brachytherapy plaque. The patient received 3 intravitreal Bevacizumab injections.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The patient had a good response to bevacizumab treatment. In fact, there was a reduction in the macular edema measured by optical coherence tomography (OCT) scan, as well as an improvement in best corrected visual acuity. There was no recurrence of macular edema, and visual acuity remained stable after 3-years follow-up.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Case report" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Caso clínico</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Paciente con un melanoma coroideo que desarrolló un edema macular secundario a maculopatía por radiación a los 75 meses del tratamiento con braquiterapia. La enferma recibió 3 inyecciones intravítreas de bevacizumab.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discusión</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La respuesta al tratamiento con bevacizumab fue favorable, con disminución del edema macular observable en la tomografía de coherencia óptica y mejoría de la agudeza visual. No se produjeron recurrencias del edema macular, y la agudeza visual permaneció estable durante un periodo de seguimiento de 3 años.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Caso clínico" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Discusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sánchez-Vicente JL, Muñoz-Morales A, Galván-Carrasco MP, Castilla-Lázpita A, Vital-Berral C, Alfaro-Juárez A, et al. Bevacizumab intravítreo en el tratamiento de la maculopatía por radiación. Arch Soc Esp Oftalmol. 2017;92:283–286.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1045 "Ancho" => 1583 "Tamanyo" => 152200 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">LE retinography. Cicatricial lesion surrounded by the laser barrier. Telangiectasiae, hemorrhages and hard exudates.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1045 "Ancho" => 1583 "Tamanyo" => 133406 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">FAG in early times of LE prior to treatment, showing macular ischemia areas.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1045 "Ancho" => 1583 "Tamanyo" => 101457 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">FAG in late times. Diffuse macular edema.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1234 "Ancho" => 2833 "Tamanyo" => 606139 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">OCT prior to treatment with bevacizumab. Presence of juxtafoveolar cysts.</p>" ] ] 4 => array:7 [ "identificador" => "fig5" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1159 "Ancho" => 2833 "Tamanyo" => 612686 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">OCT after 3 bevacizumab injections. 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