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Original article
Choroidal occlusive vasculopathy after intraarterial chemotherapy: MRI findings
Vasculopatía coroidea oclusiva tras quimioterapia intraarterial: hallazgos en la RMN
M. Roca-Cabaua,
Corresponding author
Mireia.roca.cabau@gmail.com

Corresponding author.
, J. Peralta Calvob, F. García Martínezc, A. López-Vázquezd, O. D’Annab
a Servicio de Oftalmología, Hospital Universitario de Móstoles, Madrid, Spain
b Servicio de Oftalmología Infantil, Hospital Universitario La Paz, Madrid, Spain
c Servicio de Radiología, Hospital Universitario La Paz, Madrid, Spain
d Servicio de Oftalmología, Hospital Universitario La Paz, Madrid, Spain
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in the same session&#44; but with different doses so as not to increase the toxicity of the chemotherapy drugs in the tissues&#58; higher grade eyeS with doses of melphalan between 3 and 4<span class="elsevierStyleHsp" style=""></span>mg&#44; and contralateral eyes with 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#46; The same doses of carboplatin and topotecan are used for both eyes&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">However&#44; this technique also presents complications&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Intraocular side effects after IAC were first described in 2011&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> with choroidal occlusive vasculopathy &#40;COV&#41; being the most frequent&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a> COV is an irreversible complication that can be observed as a diffuse or sectorial pigmentary alteration resulting in partial or total atrophy of the choriocapillaris and retinal pigment epithelium&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;14</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The classification of COV proposed by Munier is based on clinical observations&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The first two stages are incomplete or complete sectoral choroidopathy&#44; respectively&#46; The third stage is diffuse choroidopathy with complete choroidal atrophy affecting 50&#37; of the fundus&#46; Stage 4 includes mixed diffuse choroidopathy&#58; fundus with 50&#37; complete and 50&#37; incomplete atrophy&#46; Finally&#44; stage 5 comprises patients with diffuse choroidopathy with complete atrophy affecting more than 50&#37; of the retina&#46; Each stage is subdivided into three groups&#58; a&#41; without foveal involvement&#59; b&#41; with foveal involvement&#59; c&#41; non-assessable foveal involvement &#40;due to media opacity or foveal location of the tumour&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The consequences on ocular vascularisation have been described clinically and by fluorescein angiography&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Choroidal thinning observed on optical coherence tomography &#40;OCT&#41; has also been described in patients treated with AIC&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Regarding ocular volume&#44; there is one study showing volume reduction in eyes with retinoblastoma at diagnosis compared to the contralateral<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#59; although a reduction in axial length has also been observed after IAC&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The results of IAC are promising in terms of tumour control and globe preservation&#44; although ocular toxicity and vascular effects require further analysis&#46; In this article we analyse the adverse vascular effects observed by fundoscopy&#44; and the changes on MRI &#40;Siemens Magnetom Skyre&#44; 3 Teslas&#41; derived from the use of IAC in our sample of 37 eyes&#46; Through this case series&#44; we describe the results observed in the sample&#44; as well as the analysis of similarities and differences between patients who manifest COV and those who do not&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">A retrospective study of 37 eyes of 34 patients with retinoblastoma who were treated with IAC from 2016 to 2021&#46; In patients with retinoblastoma&#44; an initial orbital and brain MRI &#40;Siemens Magnetom Skyre&#44; 3 Teslas&#44; in T1 sequence with contrast&#41; was performed per protocol to exclude pineal tumour or extraocular disease&#46; Serial MRI scans were only performed every six months in genetically positive patients up to five years of age&#44; or in patients diagnosed at less than one year of age without genetic results&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The tumours were classified according to the international classification of retinoblastoma &#40;ICRB&#41;&#58; four patients were grade B&#44; one patient grade <span class="elsevierStyleSmallCaps">C</span>&#44; 17 grade D and 15 grade E&#46; Twenty-two patients received systemic chemotherapy with carboplatin&#44; vincristine and etoposide&#46; The remainder received IAC as first-line treatment&#46; In addition&#44; local treatments such as cryotherapy and photocoagulation were performed when necessary&#46; The presence of vitreous seeding was treated with intravitreal melphalan or topotecan&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">IAC was performed under general anaesthesia and drugs were administered via femoral artery catheterisation after heparinisation to prevent embolic complications&#46; After cannulation&#44; a 4-French catheter was introduced into the right or left common femoral artery and guided to the internal carotid artery&#46; An angiogram was performed to visualise the vascular tree and to ensure that the microcatheter was positioned at the ostium of the ophthalmic artery prior to drug infusion&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Three drugs were administered&#58; melphalan &#40;3&#8722;4<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; carboplatin &#40;40<span class="elsevierStyleHsp" style=""></span>mg&#41; and topotecan &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; After complete drug administration&#44; angiography was repeated to verify vessel integrity&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The treatment was repeated every four weeks&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Patients were examined under general anaesthesia on a monthly basis to observe tumour regression and possible complications&#46; In patients with COV&#44; the study was completed with MRI to analyse choroidal thickness and globe length&#46; To measure the anteroposterior length of the eyeball&#44; an axial T2 sequence&#44; three-dimensional volumetric acquisition SPACE sequence was used&#46; For choroidal thickness&#44; an axial T1 sequence with post-contrast fat saturation was used&#44; measuring the thickness in a macular location where the optic nerve was observed&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">COV was observed in five of the 37 eyes that received IAC &#40;13&#46;51&#37;&#41;&#44; showing grade 2 involvement and&#44; therefore&#44; complete sectoral choroidopathy with foveal involvement&#46; In some patients&#44; differences in choroidal thickness and anteroposterior asymmetry were found in axial slices on MRI images &#40;axial slices&#44; T1 sequence with contrast&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The first patient received systemic chemotherapy and two cycles of IAC in the left eye &#40;LE&#41; &#40;ICRB grade B&#41;&#46; After treatment he presented with type 1 regression of the main tumour and COV&#46; In the axial MRI slices&#44; a clear asymmetry in the ocular anteroposterior diameter was observed&#44; with 20&#46;4<span class="elsevierStyleHsp" style=""></span>mm in the left eye and 21&#46;2<span class="elsevierStyleHsp" style=""></span>mm in the right eye &#40;RE&#41;&#46; In addition&#44; choroidal thinning was observed &#40;0&#46;79<span class="elsevierStyleHsp" style=""></span>mm LE and 1&#46;1<span class="elsevierStyleHsp" style=""></span>mm RE&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The second patient had a grade D tumour &#40;ICRB&#41; in the RE&#46; After two cycles of IAC&#44; the fundus examination showed the appearance of COV&#46; No differences were observed in the MRI regarding the anteroposterior diameter of the eyeball between the two eyes &#40;RE&#58; 22&#46;4 &#47; LE 22&#46;2<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Choroidal thickness measurement was not possible due to a small retinal detachment at the posterior pole &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The third patient had a grade E tumour in both eyes &#40;BE&#41;&#44; treated with systemic chemotherapy and tandem IAC&#46; The drug doses were melphalan 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#44; topotecan 2<span class="elsevierStyleHsp" style=""></span>mg and carboplatin 40<span class="elsevierStyleHsp" style=""></span>mg in RE&#46; While in LE&#44; melphalan 4<span class="elsevierStyleHsp" style=""></span>mg&#44; topotecan 2<span class="elsevierStyleHsp" style=""></span>mg and carboplatin 40<span class="elsevierStyleHsp" style=""></span>mg were used&#46; Tumour control was achieved in BE&#59; however&#44; it should be noted that only COV was present in LE&#46; In addition&#44; choroidal thinning was observed in LE &#40;1&#46;3<span class="elsevierStyleHsp" style=""></span>mm in RE and 0&#46;75<span class="elsevierStyleHsp" style=""></span>mm in LE&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The fourth child also received tandem therapy after systemic chemotherapy &#40;bilateral retinoblastoma&#44; stage E&#44; in both eyes&#41;&#46; He required cryotherapy for control of a subretinal seeding&#46; Drug doses were as follows&#58; RE melphalan 3<span class="elsevierStyleHsp" style=""></span>mg&#44; topotecan 1<span class="elsevierStyleHsp" style=""></span>mg and carboplatin 30<span class="elsevierStyleHsp" style=""></span>mg&#46; In LE melphalan 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#44; topotecan 1<span class="elsevierStyleHsp" style=""></span>mg and carboplatin 30<span class="elsevierStyleHsp" style=""></span>mg&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Said patient developed COV in the RE where a small asymmetry in the anterior posterior ocular diameter was observed with respect to the LA &#40;RE 18&#46;3<span class="elsevierStyleHsp" style=""></span>mm&#47;LO&#58; 18&#46;7<span class="elsevierStyleHsp" style=""></span>mm&#41;&#59; despite this&#44; no differences in choroidal thickness were observed&#46; Tumour remission was achieved in both eyes &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The last patient was treated with three cycles of IAC in the RE&#46; He had COV and a clear asymmetry of the anteroposterior length of the globe&#58; RE 19&#46;1<span class="elsevierStyleHsp" style=""></span>mm compared to LE &#40;21&#46;8<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Choroidal thinning was also observed&#58; RE 1<span class="elsevierStyleHsp" style=""></span>mm and LE 1&#46;5<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">In this case series&#44; choroidal occlusive vasculopathy was observed in five of the 37 eyes &#40;13&#46;51&#37;&#41; treated with IAC&#44; similar to those seen in other publications&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;11&#44;18</span></a> The cause does not initially appear to be related to melphalan dose&#44; as three patients received 3<span class="elsevierStyleHsp" style=""></span>mg and two patients 4<span class="elsevierStyleHsp" style=""></span>mg&#46; However&#44; if we analyse patients who were treated bilaterally with tandem therapy&#44; we find COV in the eyes with high doses of melphalan &#40;3<span class="elsevierStyleHsp" style=""></span>mg and 4<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; The contralateral eye&#44; treated with doses of 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#44; did not present choroidopathy&#46; These patients treated with tandem therapy had bilateral grade E involvement in both eyes&#46; We do not have more patients with these characteristics&#44; but this finding may mean that doses of melphalan higher than 3<span class="elsevierStyleHsp" style=""></span>mg may be associated with the development of COV&#46; The doses of carboplatin and topotecan were the same in both eyes&#44; it does not appear that these drugs are related to the occurrence of COV&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The alteration in choroidal vascularisation remains unclear&#44; it could result from direct damage to the vessels during catheterisation or it could be the result of melphalan toxicity on the vascular tree or on the retinal pigment epithelium&#46; In this case series&#44; the ophthalmic artery could be accessed via the internal carotid artery &#40;ICA&#41; in four of the five patients&#46; The remaining case required access via the external carotid route due to vasospasm in the ICA&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Some patients required three cycles and others two cycles of IAC&#46; In both groups the incidence of COV was approximately the same&#44; so we do not believe that the number of catheterisations &#40;2 or 3&#41; is related to the occurrence of COV&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In four of the five patients the choroidal thickness was decreased&#44; correlating the choroidopathy observed on fundoscopy with choroidal thinning on MRI&#46; In addition&#44; in three cases ocular size was decreased in patients with COV compared to the contralateral eye&#46; It can therefore be suspected that choroidal hypoperfusion may decrease the development of the ocular globe&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Initially&#44; when pigmentary changes are seen&#44; it is difficult to determine whether they are due to incipient choroidopathy or resolution of serous detachments&#46; Perhaps MRI can be another diagnostic test to determine the presence of COV and monitor choroidal and ocular changes&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The main differential diagnosis is pigmentary changes observed after resorption of serous retinal detachments and melphalan chorioretinopathy&#46; In melphalan chorioretinopathy&#44; the visible signs appear on the second day after injection as an area with small intraretinal haemorrhages that progress to retinal atrophy with pigmentary changes around the first month&#44; and are associated with progressive chorioretinal atrophy&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">All these patients had good tumour control without the need for additional cycles of IAC or other treatments&#46; It appears that choroidopathy is a marker of treatment intensity&#44; perhaps because choriocapillary involvement also affects the vascularisation of the tumour itself&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">With regard to the COV grade&#44; our patients had a grade 2 with foveal involvement&#46; This involvement is an important marker for determining the visual prognosis of these patients&#46; In these cases&#44; due to their age the patients did not cooperate in determining visual acuity and did not tolerate contralateral eye occlusion&#44; which may indicate low vision&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">This classification makes it difficult to differentiate between the grades and does not correlate with visual acuity impairment&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">These observations provide important information as they emphasise the need to inform parents about the possible complications of IAC that can lead to vision loss in eyes with a good visual prognosis&#46; However&#44; the reason why this complication manifests only in some eyes is still unknown&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion</span><p id="par0145" class="elsevierStylePara elsevierViewall">Choroidal occlusive vasculopathy developed in five of 37 retinoblastoma eyes treated with IAC&#44; correlating in most patients with choroidal thinning and decreased ocular size on MRI&#46; Melphalan doses in patients receiving tandem therapy may be related to the occurrence of COV&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">A new classification may be needed to better correlate visual prognosis and severity of this complication&#46; In addition&#44; MRI may offer another option for the diagnosis and follow-up of COV&#46; Practitioners and parents need to be aware of the benefits and possible side effects before opting for this treatment&#46; In contrast&#44; in patients with high-grade retinoblastoma&#44; where enucleation or external radiotherapy is contemplated&#44; IAC complications are less of a concern&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Although initial results support the use of IAC as a first-line treatment&#44; studies with longer follow-up and thorough documentation of side effects are needed to understand the potential role of IAC in the treatment of retinoblastoma&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This research has not received specific support from public sector agencies&#44; the commercial sector or non-profit organisations&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">No conflicts of interest were declared by the authors&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">To evaluate magnetic resonance imaging &#40;MRI&#41; findings in patients suffering choroidal occlusive vasculopathy &#40;COV&#41; after intra-arterial chemotherapy &#40;IAC&#41; for retinoblastoma&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A retrospective study of 37 eyes of 34 patients receiving IAQ between 2016 to 2021 as primary or secondary treatment for retinoblastoma was conducted&#46; Twenty-two patients received systemic chemotherapy with carboplatin&#44; vincristine and etoposide&#46; The rest received IAC as primary treatment&#46; The drugs administered were melphalan &#40;3&#8722;4<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; carboplatin &#40;40<span class="elsevierStyleHsp" style=""></span>mg&#41; plus topotecan &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; The patients were examined under general anaesthesia every month to observe tumor regression and possible complications of the treatment&#46; For the patients with COV an MRI was obtained to analyse the choroidal thickness and axial ocular length&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A COV was observed in 5 of the 37 eyes receiving IAC &#40;13&#44;51&#37;&#41;&#44; all of them with a complete sectorial choroidopathy not sparing the fovea &#40;grade 2&#41;&#46; In 4 of the 5 patients the choroidal thickness was decreased and in three cases the size of the eye which presented COV was clearly smaller than the contralateral eye&#46; Tumor control was archived in all 5 patients&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">In our cases COV was associated with reduction of thinning of choroid and eye length in the MRI&#46; A new classification maybe needed to correlate better with the severity of the complication affecting the fovea&#46; Although early results generally are favorable to the use of IAC&#44; longer follow up and scrupulous documentation of side effects will be necessary to know the true role of IAC for retinoblastoma&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Evaluar los hallazgos en las im&#225;genes de resonancia magn&#233;tica nuclear &#40;RMN&#41; en pacientes con vasculopat&#237;a coroidea oclusiva &#40;VCO&#41; tras quimioterapia intraarterial &#40;QIA&#41; por retinoblastoma&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo de 37 ojos de 34 pacientes que recibieron QIA entre 2016 y 2021 como tratamiento de primera o segunda l&#237;nea del retinoblastoma intraocular&#46; De estos pacientes&#44; 22 recibieron quimioterapia sist&#233;mica y el resto QIA como primera l&#237;nea&#44; con melfal&#225;n &#40;3&#8722;4<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; carboplatino &#40;40<span class="elsevierStyleHsp" style=""></span>mg&#41; y topotecan &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; Los pacientes fueron examinados cada mes para observar la regresi&#243;n tumoral y posibles complicaciones de los tratamientos&#46; A los pacientes que presentaron VCO se les realizaron estudios con RMN para evaluar el grosor coroideo y la longitud del globo ocular&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; VCO en cinco de los 37 ojos &#40;13&#44;51&#37;&#41;&#44; todos ellos con una coroidopat&#237;a sectorial completa con afectaci&#243;n foveal &#40;grado 2&#41;&#46; En cuatro de los cinco pacientes el grosor coroideo se vio disminuido&#44; mientras que en tres casos el tama&#241;o del globo afectado era claramente inferior&#46; El control tumoral fue posible en todos los casos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">En esta muestra&#44; la VCO se asocia con adelgazamiento coroideo y diminuci&#243;n del tama&#241;o ocular en la RMN&#46; Puede ser necesaria una nueva clasificaci&#243;n para correlacionar mejor la severidad de la coroidopat&#237;a que afecta a la f&#243;vea&#46; Los resultados iniciales son favorables respecto al uso de la QIA&#59; aunque es necesaria la realizaci&#243;n de estudios a largo plazo y una documentaci&#243;n exhaustiva para valorar tanto el papel de la QIA&#44; como los efectos derivados de ella&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Roca-Cabau M&#44; Peralta Calvo J&#44; Garc&#237;a Mart&#237;nez F&#44; L&#243;pez-V&#225;zquez A&#44; D&#8217;Anna O&#46; Vasculopat&#237;a coroidea oclusiva tras quimioterapia intraarterial&#58; hallazgos en la RMN&#46; Arch Soc Esp Oftalmol&#46; 2022&#59;97&#58;620&#8211;625&#46;</p>"
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    "bibliografia" => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            1 => "A&#46; Mashayekhi"
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                  ]
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Retinoblastoma control with primary intra-arterial chemotherapy&#58; outcomes before and during the intravitreal chemotherapy era"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;L&#46; Shields"
                            1 => "A&#46;E&#46; Alset"
                            2 => "E&#46;A&#46;T&#46; Say"
                            3 => "E&#46; Caywood"
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                          ]
                        ]
                      ]
                    ]
                  ]
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                      "doi" => "10.3928/01913913-20160719-04"
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                      "titulo" => "The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Yamane"
                            1 => "A&#46; Kaneko"
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                          ]
                        ]
                      ]
                    ]
                  ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma &#40;chemosurgery&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46;H&#46; Abramson"
                            1 => "I&#46;J&#46; Dunkel"
                            2 => "S&#46;E&#46; Brodie"
                            3 => "B&#46; Marr"
                            4 => "Y&#46;P&#46; Gobin"
                          ]
                        ]
                      ]
                    ]
                  ]
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                      "Revista" => array:6 [
                        "tituloSerie" => "Ophthalmology"
                        "fecha" => "2010"
                        "volumen" => "117"
                        "paginaInicial" => "1623"
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                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0040"
              "etiqueta" => "8"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46;L&#46; Munier"
                            1 => "M&#46; Beck-Popovic"
                            2 => "A&#46; Balmer"
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                        ]
                      ]
                    ]
                  ]
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            ]
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Conservative management of retinoblastoma&#58; challenging orthodoxy without compromising the state of metastatic grace&#46; &#8220;Alive&#44; with good vision and no comorbidity&#8221;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "F&#46;L&#46; Munier"
                            1 => "M&#46; Beck-Popovic"
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                        ]
                      ]
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                  ]
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            ]
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;C&#46; Eagle"
                            1 => "C&#46;L&#46; Shields"
                            2 => "C&#46; Bianciotto"
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                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archophthalmol.2011.223"
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                        "tituloSerie" => "Arch Ophthalmol"
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                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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            ]
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "titulo" => "Fluorescein angiographic findings after intra-arterial chemotherapy for retinoblastoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; Bianciotto"
                            1 => "C&#46;L&#46; Shields"
                            2 => "J&#46;C&#46; Iturralde"
                            3 => "A&#46; Sarici"
                            4 => "P&#46; Jabbour"
                            5 => "J&#46;A&#46; Shields"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ophtha.2011.09.040"
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                        "volumen" => "119"
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                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
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              "etiqueta" => "12"
              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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