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Retinografía normal del ojo derecho. B. Retinografía del ojo izquierdo: tubérculo coroideo que se presenta como un nódulo solitario, blanco-amarillento, de bordes irregulares, subretiniano, no asociado con desprendimiento seroso de retina. Sugiere diseminación hematógena de la tuberculosis.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">C. Fase arteriovenosa tardía de la angiografía fluoresceínica del ojo izquierdo mostrando aumento de la fluorescencia en tiempos tardíos. D. SD-OCT: no se observa elevación de la retina neurosensorial ni asociación con desprendimiento seroso de retina.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V.M. Asensio-Sánchez, L. Díaz-Cabanas, A. Martín-Prieto, B. Haro-Álvarez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "V.M." "apellidos" => "Asensio-Sánchez" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Díaz-Cabanas" ] 2 => array:2 [ "nombre" => "A." 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Case report" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "151" "paginaFinal" => "154" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "A propósito de un caso de hamartoma retiniano adyacente a cabeza de nervio óptico en un caso de esclerosis tuberosa" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2270 "Ancho" => 2667 "Tamanyo" => 642496 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">OCT showing subretinal fluid exudation from the papilla to the fovea.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F. 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Asensio-Sánchez, L. Díaz-Cabanas, A. Martín-Prieto, B. Haro-Álvarez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "V.M." "apellidos" => "Asensio-Sánchez" "email" => array:1 [ 0 => "victor_asensio@orangemail.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Díaz-Cabanas" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Martín-Prieto" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Haro-Álvarez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Oftalmología, Hospital Clínico Universitario, Valladolid, 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" => "Tubérculo coroideo asintomático en un paciente con enfermedad de Crohn en tratamiento con adalimumab" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 752 "Ancho" => 950 "Tamanyo" => 69798 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Marginal retraction and depigmentation of the choroidal tuber after 6 months of antituberculostatic treatment. The lesion shows improved edges.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Crohn's disease (CD) is an intestinal inflammatory disease that could have uncertain and severe prognosis.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Biological therapy is a first-line treatment to induce remission in the severest forms of CD.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Adalimumab is an anti-tumor necrosis factor α (TNF-α) monoclonal antibody which, by diminishing the effect of the immune system, increases the risk of infections such as tuberculosis (TB).<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> Despite the increased incidence of TB,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> choroidal tubers are rare and generally asymptomatic, except in immunodepressed patients.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The present article describes an unusual case with very few reports of an asymptomatic choroidal tuber in the context of a miliary pulmonary TB in a patient with severe CD treated with adalimumab.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Clinic case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">Male, 48, with severe ileocecal CD treated with Humira<span class="elsevierStyleSup">®</span> (adalimumab, AbbVie Bioresearch Center. 100 Research Drive. Worcester, MA 01605, USA), 40<span class="elsevierStyleHsp" style=""></span>mg subcutaneous every 2 weeks with prior screening for biologic medicaments according to standard practice (chest X-ray, serology for hepatitis B and C virus, herpes simplex virus, herpes zoster virus, cytomegalovirus, HIV and Mantoux). During the month of treatment the patient was admitted due to asthenia, loss of appetite and fever of up to 39<span class="elsevierStyleHsp" style=""></span>°C with one week evolution, predominantly during the evening. A study for fever of unknown cause was requested consisting in Mantoux, urine and blood culture, chest X-ray, viral serology, Brucella and blood culture for mycobacteria as well as echocardiogram for discarding endocarditis. It was considered that the patient had high risk of contracting TBC, and therefore of Quantiferon-TB test and Mantoux were taken. The first test was positive and the second test 48<span class="elsevierStyleHsp" style=""></span>hours later revealed a erythema and at 72<span class="elsevierStyleHsp" style=""></span>hours a 10<span class="elsevierStyleHsp" style=""></span>mm induration. Chest X-ray showed bilateral micronodular pattern, particularly at the hilar and paratracheal level, all of which indicated disseminated miliary TB (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Anti-TNF-α treatment was withdrawn, introducing azathioprine 2.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day. Anti-tuberculosis shock treatment was initiated with isoniazide 300<span class="elsevierStyleHsp" style=""></span>mg/day, rifampicin 600<span class="elsevierStyleHsp" style=""></span>mg/day, pyrazinamide 40<span class="elsevierStyleHsp" style=""></span>mg/kg/day and streptomycin 15<span class="elsevierStyleHsp" style=""></span>mg/kg/day during 4 months, followed by isoniazide and rifampicin for 12 additional months. One week after admission, following the protocol of the infectious diseases department, ophthalmological examination was carried out producing a visual acuity of 1 in both eyes and absence of anterior segment inflammation. In addition, right eye fundus was normal (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), while the left eye fundus revealed a mass having 2/3 disk diameter, temporal-superior location vis-à-vis the optic disk, whitish yellow color and slightly uneven but well defined contour (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). No inflammation, exudation, hemorrhage or associated retinal detachment were observed. Fluorescein angiography revealed slight early fluorescence with moderate-intense late hyperfluorescence (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>C). Optical coherence tomography did not show elevation of the mass or association with serous retinal detachment. The choroids could not be seen in the image because it did not appear complete due to poor patient cooperation (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D). Differential diagnostic included syphilis, toxoplasmosis, sarcoidosis, brucellosis, choroidal hemangioma, metastasis and amelanotic melanoma. Angiotensin-converting enzyme levels were normal. Similarly, serological studies for HIV, syphilis, toxoplasma and brucellosis were negative. Ocular echography did not show alterations. After 6 months a slow but significant reduction of the choroidal tuber size was observed (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">In the 19th century TB was one of the most severe infectious diseases.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> In 2013, 9 million people contracted the disease and 1.5 million died due to TB throughout the world.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Paradoxically, increased incidence in Western countries is due to improved social and health conditions and longer life expectancy as well as the increase of tumors, increased amount of transplants, therapies such as biological therapy that has increased its indications and the globalized immigration of malnourished populations.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> The immune system is essential to control tuberculosis infection, wherein TNF-α plays a crucial role.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Anti-TNF-α are utilized as first-line therapy in patients with complicated CD.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Adalimumab is an anti-TNF-α monoclonal antibody which, in contrast with other biologic agents, is administered subcutaneously, thus involving obvious advantages for the patient and hospital structures.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> However, adverse effects related with this therapy such as reactions against infusion, demyelinization disease, self-immune reactions and infections such as tuberculosis<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> should always be taken into account. Intraocular tuberculosis could be the result of direct infection, hematogenous dissemination, or could be induced by immune hypersensitivity response type IV which could compromise any ocular structure.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Most common clinic presentation is posterior uveitis, particularly choroidal tuberculosis.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> It has been described that multiple choroidal tubers are the most common intraocular expression of tuberculose posterior uveitis.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> However, it is rare to find a tuber in the choroids except in patients infected by the human immunodeficiency virus.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Tubers present as uni-or bilateral yellowish white lesions with poorly defined edges, solitary or in small groups located deeply within the choroids and posterior pole<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,8</span></a> and are generally associated with vitreous inflammation and subretinal fluid.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,8</span></a> However, in immunodepressed patients (HIV, biological therapy), choroidal tubers could be typically nonreactive, with absence or slight vitreous inflammation and, due to their deep location in the choroids, could go unnoticed as in the case described herein.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The present patient did not exhibit specific signs in OCT although an adequate OCT image could not be obtained due to the fatigue shown by the patient. OCT could be useful to differentiate choroidal tuberculose granulomas from non-inflammatory diseases with similar clinic appearance. An OCT section over the granuloma shows a distinctive sign, i.e., the link between the choriocapillary-pigment epithelium layer and the neurosensory retina (contact sign).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> This sign is associated with the presence of surrounding subretinal fluid and inflammatory infiltrates in the deep retina.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,9</span></a> The contact sign and subretinal fluid were not observed in the present case, where the choroidal tuberculosis diagnostic was established by means of Quantiferon-TB and positive Mantoux. Chest X-ray confirmed systemic tuberculosis while laboratory and imaging tests excluded other etiologies. The tuber size diminished considerably with specific treatment, without exhibiting inflammation or exudation.</p><p id="par0030" class="elsevierStylePara elsevierViewall">TB screening should be very exhaustive, including epidemiological antecedents and finding out if any previous vaccine was received, as well as assessing changes in the sociological environment of the patient. In a review and meta-analysis, Zhang et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> indicated that the risk of tuberculosis could increase significantly in patients treated with TNF-α, antagonists, particularly if they have rheumatoid arthritis. When TB is diagnosed, the therapeutic approach is to withdraw biologic therapies and initiate anti-TB treatment. It does not seem necessary to withdraw corticoids or immunomodulators. Anti-TNF-α should not be resumed in patients with active infection before 2 months since the anti-TB treatment.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Due to the re-emergence of tuberculosis and the increased indications for biological therapy, ophthalmologists should be aware that a solitary choroidal tuber could be diagnosed in ophthalmologically asymptomatic patients and that many do not report said treatments, making exhaustive clinic history essential.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interests</span><p id="par0040" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres993669" "titulo" => "Abstract" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Case report" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec957106" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres993668" "titulo" => "Resumen" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Caso clínico" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec957105" "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:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-03-25" "fechaAceptado" => "2017-06-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec957106" "palabras" => array:5 [ 0 => "Adalimumab" 1 => "Biological therapy" 2 => "Miliary tuberculosis" 3 => "Choroidal tubercle" 4 => "Crohn's disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec957105" "palabras" => array:5 [ 0 => "Adalimumab" 1 => "Terapia biológica" 2 => "Tuberculosis miliar" 3 => "Tubérculo coroideo" 4 => "Enfermedad de Crohn" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Adalimumab, an anti-tumor necrosis factor alpha therapy for active Crohn's disease (CD), is associated with increased risks of tuberculosis infection.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Case report</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The case is presented of a 48 year-old male with active CD on treatment with adalimumab. After three months, he developed a miliary pulmonary tuberculosis infection, with a solitary non-reactive choroidal tubercle temporal-superior to the optic disk being found in an ophthalmological study. Fluorescein angiography showed late hyperfluorescence in a staining pattern. Optic coherence tomography showed a flat mass without serous retinal detachment. The choroidal tubercle slowly regressed with antituberculosis therapy.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Discussion</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Choroidal tubercles with no vitreo-retinal symptomatology can be present in patients with CD and on treatment with adalimumab.</p></span>" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Case report" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducción</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Adalimumab, un antifactor de necrosis tumoral que se utiliza en la enfermedad de Crohn activa (EC), se asocia con un mayor riesgo de tuberculosis.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Caso clínico</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Se describe el caso de un varón de 48 años con EC activa en tratamiento con adalimumab. Después de 3 meses desarrolló una tuberculosis pulmonar miliar, y en un estudio oftalmológico se encontró un tubérculo coroideo no reactivo solitario temporal superior al disco óptico. La angiofluoresceingrafía mostró hiperfluorescencia tardía. Con la tomografía de coherencia óptica se observó una masa plana sin desprendimiento seroso de retina. El tubérculo coroideo regresó lentamente con la terapia antituberculosa.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discusión</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En pacientes con EC y en tratamiento con adalimumab, un tubérculo coroideo puede presentarse sin sintomatología vítreo-retiniana.</p></span>" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Caso clínico" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Discusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Asensio-Sánchez VM, Díaz-Cabanas L, Martín-Prieto A, Haro-Álvarez B. Tubérculo coroideo asintomático en un paciente con enfermedad de Crohn en tratamiento con adalimumab. Arch Soc Esp Oftalmol. 2018;93:147–150.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 942 "Ancho" => 950 "Tamanyo" => 96427 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Chest X-ray with micronodular or miliary pattern, showing small roundish nodules with clear edges distributed in both pulmonary fields, 3 months after initiating therapy with adalimumab.</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" => 2958 "Ancho" => 2833 "Tamanyo" => 869480 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">(A) Normal right eye retinography. (B) Left eye retinography, showing choroidal subretinal tuber presenting as a solitary yellowish white nodule with uneven shape not associated with serous retinal detachment, suggesting hematogenous dissemination of tuberculosis.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(C) late arteriovenous phase of left eye fluorescein angiography showing increased fluorescence in late times. (D) SD-OCT: no neurosensory retina elevation or association with serous retinal detachment.</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" => 752 "Ancho" => 950 "Tamanyo" => 69798 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Marginal retraction and depigmentation of the choroidal tuber after 6 months of antituberculostatic treatment. 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