microRNA-144 functions as a diagnostic and prognostic marker for retinoblastoma

OBJECTIVES: Retinoblastoma (RB) is a highly malignant eye tumor with a low survival rate and a high metastatic rate. The current work was designed to investigate the potential roles of microRNA-144 (miR-144) in the diagnosis and prognosis of RB. METHODS: miR-144 expression levels in RB tissues and adjacent normal tissues, as well as serum samples from RB patients and healthy controls were measured. The association between miR-144 expression levels and clinical features were analyzed. Moreover, diagnostic and prognostic values of miR-144 in RB were verified by receiver operating characteristic analysis and Kaplan-Meier survival assays. RESULTS: The expression level of miR-144 was markedly decreased in tumor tissues of RB patients, and the expression level of miR-144 was positively associated with tumor size and metastasis in RB patients. Moreover, miR-144 can distinguish tumor tissues from normal tissues with high specificity and sensitivity, and RB patients with lower miR-144 expression have shorter overall and disease-free survival rates than those with higher miR-144 expression. Alternatively, miR-144 also decreased in the serum of RB patients in comparison with healthy subjects, and miR-144 expression levels in the tissue samples and serum were positively correlated. Furthermore, miR-144 levels in the serum of RB patients sensitively distinguished RB patients from healthy controls. CONCLUSIONS: miR-144 expression was downregulated in serum and tissue samples of RB patients and may function as a diagnostic and prognostic marker for RB.

Coats disease associated with vasoproliferative tumor treated with cryotherapy and intravitreal injections of triamcinolone / Doença de Coats associada a tumor vasoproliferativo tratada com crioterapia e injeções intravítreas de triancinolona

Abstract Report of a case of Coats disease associated with retinal vasoproliferative tumor in a young female patient with two peripheral vascularized tumors and lipid exudation involving the macula and peripapillary region with serous retinal detachment areas and pre-papillary fibrous proliferation. The proposed and performed treatment was the intravitreal injection of triamcinolone acetonide to decrease the tumor exudation, followed by photocoagulation of the peripheral areas of telangiectasia without subretinal fluid and cryotherapy of the tumors. Despite that this is a rare and difficult to treat combination, in this case report, success was obtained in receding the tumor masses and reapplying the retina, leading to anatomic and visual stabilization.

Resumo Relato de um caso de Doença de Coats associada a tumor vasoproliferativo de retina em uma paciente jovem com duas tumorações vascularizadas periféricas e exsudação lipídica acometendo mácula e região peripapilar com áreas de descolamento de retina seroso e proliferação fibrosa pré-papilar. O tratamento proposto e realizado foi a injeção intra-vítrea de triancinolona para diminuir a exsudação do tumor, seguida de fotocoagulação periférica das áreas de telangiectasia sem fluido subretiniano e criocoagulação dos tumores. Apesar de se tratar de uma associação rara e de difícil tratamento, neste relato de caso, obteve-se êxito em regredir as massas tumorais e reaplicar a retina, levando à estabilização anatômica e visual.

A força da informação sobre retinoblastoma para a família da criança / La fuerza de la información sobre retinoblasma para la familia del niño / The strength of information on retinoblastoma for the family of the child

Resumo Objetivo: Compreender a necessidade de informação da família da criança com retinoblastoma. Métodos: Estudo qualitativo fundamentado no Modelo do Cuidado Centrado no Paciente e na Família. Participaram famílias de crianças em tratamento em uma instituição referência em oncologia pediátrica. A Análise Qualitativa de Conteúdo guiou a coleta e análise dos dados. Resultados: "A força da informação sobre retinoblastoma para a família da criança" revela o valor que a família atribui à informação sobre a doença da criança, em um tempo de intenso sofrimento; os caminhos que realiza para obter as informações; e os elementos que considera essenciais para se sentir atendida em seu direito. Conclusão: Torna-se primordial que a oferta de informações respeite o tempo da família, seja honesta, contemple as perspectivas de futuro para a criança, em um espaço dialógico. Dessa maneira, promove-se uma prática fundamentada no Modelo do Cuidado Centrado no Paciente e na Família.

Resumen Objetivo: Comprender la necesidad de información de la familia del niño con retinoblasma. Métodos: Estudio cualitativo, fundamentado en el Modelo de Cuidado Centrado en el Paciente y la Familia. Participaron familias de niños tratados en institución de referencia en oncología pediátrica. Datos recolectados y analizados mediante Análisis Cuantitativo de Contenido. Resultados: "La fuerza de la información sobre retinoblasma para la familia del niño" revela el valor que la familia atribuye a la información sobre la enfermedad del niño en un momento de intenso sufrimiento; los caminos que transita para obtener información; y los elementos que considera esenciales para sentirse atendida en su derecho. Conclusión: Resulta esencial que la oferta de información respete los tiempo familiares, sea honesta, contemple las perspectivas de futuro para el niño, en un espacio dialógico. De ese modo se promueve una práctica fundamentada en el Modelo de Cuidado Centrado en el Paciente y la Familia.

Abstract Objective: To understand the need for information from the family members of children with retinoblastoma. Methods: A qualitative study based on the Patient and Family Centered Care Model. Families of children undergoing treatment at a referral institution in pediatric oncology participated. Qualitative content analysis guided the data collection and analysis. Results: The strength of information on retinoblastoma for the family of these children reveals the value the family assigns to the information about the child's illness during a time of intense suffering; the paths they take to obtain the information; and, the elements considered to be essential to feel fulfilled in their own right. Conclusion: Provision of information that respects the family's time is essential; it must be honest, and contemplate future perspectives for the child, in a dialogical space. Thus, a practice based on the Patient and Family Centered Care Model is promoted.

Retinoblastoma infantil, deteccion temprana de un caso inusual / Children's retinoblastoma early detection in an unusual case

El retinoblastoma es el cáncer de retina más frecuente en la infancia. Representa el 4% de los tumores en menores de 15 años. Su diagnóstico se realiza generalmente entre los 12 y 18 meses de vida, con buen pronóstico si no se ha diseminado. Objetivo: resaltar la importancia de la sospecha clínica para detección temprana de esta enfermedad. Caso clínico: paciente masculino de 4 meses de vida, procedente de Tegucigalpa, Honduras; con alteración en el reflejo pupilar del ojo izquierdo (leucocoria), acompañado de estrabismo divergente del mismo ojo. Fue evaluado por oftalmología y remitido al Hospital Escuela Universitario por sospecha de retinoblastoma de ojo izquierdo. Al examinar fondo de ojo se encontró lesión de 4 mm que ocupa 2/3 partes de la retina, por lo que se realizó tomografía axial computarizada cerebral y de órbita de ojo izquierdo, que reportó hipotrofia cortical frontotemporal bilateral y masa sólida calcificada que no se extiende fuera del globo ocular. Se indicó resonancia magnética nuclear de órbita, encontrándose masa hipodensa irregular en cámara posterior de ojo izquierdo. Posteriormente se realizó retino cámara, mostrando lesión que cubre casi totalidad de la retina. Con estos hallazgos el Servicio de Oftalmología Pediátrica, lo intervino quirúrgicamente realizando enucleación de ojo afectado; sin complicaciones, evolución satisfactoria y seguimiento en consulta externa de Hematoncológica Pediátrica. Conclusión: en este caso, la enfermedad se diagnosticó en etapa temprana, algo que generalmente no ocurre, logrando salvar la vida del paciente y evitó la diseminación a órganos adyacentes.

Systematic review of the current status of programs and general knowledge of diagnosis and management of retinoblastoma / Revisión sistemática del estado actual de los programas y conocimiento general de la diagnosis y manejo de retinoblastoma

Abstract: Background: This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients with Rb at select hospitals with Rb programs or that treat and refer patients with Rb, and identified the gaps in practice. We propose solutions to improve diagnosis, provide adequate treatment, and improve patient uptake. Methods: A general review was conducted on PubMed of peer-reviewed literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb programs at seven hospitals in Mexico were contacted for data available on their patients with Rb. Results: Five hospitals provided clinical data on 777 patients with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4% underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced intraocular stage of development. Knowledge of the disease is limited, despite the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment guidelines and is developing a national Rb registry. Especially in the Southern states, prevalence and outcomes are comparable to African and Asian countries, and only few patients are referred to national treatment centers. Only three institutions have comprehensive Rb programs. Conclusions: There is an immediate need in Mexico to expand primary care providers' knowledge of Rb and to expand and upgrade current Rb programs to meet the needs of the population adequately. Diagnosis and care of Rb patients in Mexico can also be improved by the establishment of a national Rb registry and a national early detection program, and by increased use of the national treatment protocol.

Resumen: Introducción: Esta es una revisión sistemática de los conocimientos actuales del retinoblastoma (Rb) y sus implicaciones en los centros de referencia más importantes del país. Se presenta un análisis situacional de los programas de Rb en México, se identificaron las brechas en la práctica, y se proponen soluciones para mejorar el diagnóstico, tratamiento y referencia oportuna de pacientes. Métodos: Se realizó una revisión general de la literatura publicada sobre Rb en México a través de PubMed. Los datos sociodemográficos de pacientes con Rb fueron obtenidos a través de los directores de programas de retinoblastoma en siete hospitales. Resultados: Casi una tercera parte de los casos Rb se diagnostican en estadios avanzados. A pesar de la existencia del Grupo Mexicano de Retinoblastoma, el conocimiento de esta patología entre los médicos es limitado. Las diferencias en el tratamiento son notorias en el sur del país, donde la prevalencia y los resultados son comparables con África y Asia. Solamente tres instituciones a nivel nacional tienen un programa establecido de Rb. Conclusiones: Existe la necesidad inmediata de consolidar los programas de Rb para cubrir las necesidades reales de la población. Se requiere mejorar la educación del médico de primer contacto, establecer el registro nacional de casos y el programa de detección temprana, establecer los programas de salvamento ocular nacional, y reforzar las instituciones que brindan tratamiento.

Immunohistochemical analysis of retinoblastoma cell phenotype using neuronal and glial cell markers / Análise imuno-histoquímica do fenótipo de células de retinoblastoma utilizando marcadores de células neuronais e gliais

ABSTRACT Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP). Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous seeding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Results: Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells) and MAP2 (90% of cells in both lines). GFAP was completely negative in both cell lines. Conclusion: The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.

RESUMO Objetivos: Este estudo visa determinar a origem do retinoblastoma em um número de casos e correlacionar essos achados com fatores prognósticos e histopatológicos conhecidos. Métodos: Trinta e nove casos de retinoblastoma foram diagnosticados e analisados com imuno-histoquímica usando marcadores de anticorpos monoclonais contra as células de retina imaturas (SOX-2: SRY-box containing gene 2), contra as células da retina maturas (MAP2: microtubule -associated protein 2) e contra as células gliais maturas (GFAP: glial fibrillar acidic protein). Foram avaliadas características microscópicas dos casos (grau de diferenciação, presença de semeadura vítrea, invasão de coroide/esclera, nervo óptico e câmara anterior). Duas linhas celulares de retinoblastoma (WERI-1 e Y79) também foram testadas, utilizando os três marcadores. Resultados: A expressão de SOX-2 foi positiva em 97,4% dos casos de retinoblastoma, enquanto MAP2 foi positivo em 59% dos casos. GFAP foi apenas positivo no estroma (astrócitos reativos). Não houve correlação entre preditores histopatológicos e marcadores imunohistoquímicos avaliados. As linhagens celulares mostraram positividade para SOX-2 (90% em WERI-1 e 70% das células Y79). Ambas as linhagens celulares se mostraram fortemente positivas con MAP2 (90%), enquanto não houve expressão de GFAP em nenhuma das linhas celulares estudadas. Conclusões: A maioria das células de retinoblastoma desta série de casos expressa marcadores de células retinianas imaturas, além de marcadores de células maduras. As linhas celulares Y79 e WERI-1 apresentaram imunomarcação para ambos os marcadores neurais em percentagens semelhantes a dos casos avaliados. Portanto, estes resultados confirmam a origem neural do tumor em particular. Alem disso, a ausência de células positivas para GFAP no tumor descarta diferenciação de astrócitos em retinoblastoma.

Blood flow velocity in monocular retinoblastoma assessed by color doppler

OBJECTIVE: To analyze the flow of retrobulbar vessels in retinoblastoma by color Doppler imaging. METHODS: A prospective study of monocular retinoblastoma treated by enucleation between 2010 and 2014. The examination comprised fundoscopy, magnetic resonance imaging, ultrasonography and color Doppler imaging. The peak blood velocities in the central retinal artery and central retinal vein of tumor-containing eyes (tuCRAv and tuCRVv, respectively) were assessed. The velocities were compared with those for normal eyes (nlCRAv and nlCRVv) and correlated with clinical and pathological findings. Tumor dimensions in the pathological sections were compared with those in magnetic resonance imaging and ultrasonography and were correlated with tuCRAv and tuCRVv. In tumor-containing eyes, the resistivity index in the central retinal artery and the pulse index in the central retinal vein were studied in relation to all variables. RESULTS: Eighteen patients were included. Comparisons between tuCRAv and nlCRAv and between tuCRVv and nlCRVv revealed higher velocities in tumor-containing eyes (p <0.001 for both), with a greater effect in the central retinal artery than in the central retinal vein (p =0.024). Magnetic resonance imaging and ultrasonography measurements were as reliable as pathology assessments (p =0.675 and p =0.375, respectively). A positive relationship was found between tuCRAv and the tumor volume (p =0.027). The pulse index in the central retinal vein was lower in male patients (p =0.017) and in eyes with optic nerve invasion (p =0.0088). CONCLUSIONS: TuCRAv and tuCRVv are higher in tumor-containing eyes than in normal eyes. Magnetic resonance imaging and ultrasonography measurements are reliable. The tumor volume is correlated with a higher tuCRAv and a reduced pulse in the central retinal vein is correlated with male sex and optic nerve invasion.

Trilateral retinoblastoma with unilateral eye involvement / Retinoblastoma trilateral com acometimento ocular universal

SummaryRetinoblastomas (RB) are the main forms of intraocular tumor in childhood, with a worldwide incidence of 1 case per 15,000 to 20,000 live births. Trilateral RB (RBT) is a rare combination of unilateral or bilateral RB with a midline intracranial neoplasm of neuroblastic origin, usually found in the pineal region or the suprasellar region, presenting variable incidence of 0.5% up to 6% among patients with RB. The article reports a case of unilateral RBT in a patient treated at Hospital A.C.Camargo.

ResumoO retinoblastoma (RB) é a principal forma de tumor intraocular na infância, apresentando uma incidência mundial de 1 caso em cada 15 mil a 20 mil nascidos vivos. O RB trilateral (RBT) é uma rara combinação de RB unilateral ou bilateral com uma neoplasia da linha média intracraniana de origem neuroblástica, geralmente na região da glândula pineal ou na região suprasselar, apresentando incidência variável de 0,5 a 6% entre pacientes com RB. O artigo relata o caso de uma paciente com RBT com acometimento unilateral atendida no Hospital A.C.Camargo.

Evaluación de secuelas visuales y cosméticas del tratamiento conservador con terapia radiante externa en pacientes con retinoblastoma bilateral en el Hospital de Pediatría Garrahan / Assessment of visual and cosmetic sequelae of conservative treatment of external beam radiation of patients with bilateral retinoblastoma at the Pediatric Hospital Garrahan

El Retinoblastoma es la neoplasia ocular más frecuente en pediatría. La Terapia radiante externa fue hasta hace una década el tratamiento conservador de elección. Luego se incluyó la quimio reducción; en un intento de evitar la radioterapia externa y sus complicaciones. En este estudio retrospectivo evaluamos los resultados del tratamiento conservador con terapia radiante externa o con quimio reducción en el servicio de oftalmología del Hospital Nacional de Pediatría Juan P. Garrahan, desde 1987 a 2009. De un total de 571 pacientes con diagnóstico de Retinoblastoma, 341 fueron unilaterales y 217 bilaterales. De estos últimos se analizaron 166 pacientes cuya edad media al diagnostico fue de 12 meses. Se trataron 332 ojos de 166 pacientes con Retinoblastoma bilateral, 157 ojos (47,3%) recibieron quimioreducción como tratamiento inicial, 115 ojos (34,6%) fueron enucleados al inicio, 45 ojos (13,6%) recibieron radioterapia externa como único tratamiento y 15 ojos (4,5%) recibieron tratamiento local solo (laser o crioterapia) como primera elección. Se analizaron los datos con el programa estadístico STATA 12.0 stataCorp Texas.USA. La agudeza visual final fue superior a 20/70 en el 51,5% de los pacientes e inferior en el 48,5%. Se encontró una relación significativa (p=0,005) entre el estadio al diagnóstico y la agudeza visual final; los pacientes con discapacidad visual se presentaron con estadios avanzados. Se evaluaron todas las orbitas enucleadas (157); de ellas el 74,5% recibieron radioterapia externa antes o después de la enucleación. El 24,8% de las orbitas irradiadas presentaron deformidad de la cavidad, con mala adaptación de prótesis y retracción orbitaria, el 70,1% presentaron cambios que permitían una adaptación de prótesis aceptable con alguna limitación de movilidad y solo 6 orbitas (5,12%) presentaban una muy buena cavidad para adaptación cosmética. Cuarenta de 157 orbitas enucleadas no recibieron radioterapia en ningún momento (25,5%), el 92,5% de ellas presentaron buena adaptación y solo el 7,5% tuvieron problemas de adaptación debido a complicaciones postoperatorias. El diagnóstico precoz, el tratamiento oportuno, y el uso de quimio reducción como terapia inicial en Retinoblastoma intraocular, permiten aumentar la tasa de preservación del globo ocular y reducen o eliminan la necesidad de recibir Terapia radiante externa, evitando sus secuelas (AU)

Retinoblastoma is the most common ocular neoplasia in childhood. External beam radiation therapy was the conservative treatment of choice until a decade ago. Subsequently, chemoreduction was added trying to avoid external beam radiation therapy and its complications. In this retrospective study we assess the results of conservative therapy with external beam radiation therapy or with chemoreduction at the Department of Ophthalmology at the Pediatric Hospital Juan P. Garrahan between 1987 and 2009. Of a total of 571 patients with a diagnosis of retinoblastoma, 341 had unilateral and 217 bilateral retinoblastoma. Of the latter patients, 166 patients were analyzed with a mean age at diagnosis of 12 months. Overall, 332 eyes of 166 patients with bilateral retinoblastoma were treated; at initial treatment 157 eyes (47.3%) underwent chemoreduction, 115 eyes (34.6%) were enucleated, 45 eyes (13.6%) underwent external beam radiation therapy as the only treatment, and 15 eyes (4.5%) only received local treatment (laser or cryotherapy) as a first choice. Data were analyzed using STATA 12.0 stataCorp Texas.USA. Final visual acuity was more than 20/70 in 51.5% and less in 48.5% of the patients. A significant relationship (p=0.005) between stage at diagnosis and final visual acuity was found; patients with visual impairment presented with advanced stages. All enucleated orbits were assessed (157); 74.5% underwent external beam therapy before or after enucleation. Of all irradiated orbits, 24.8% presented with cavity deformity, poor prosthesis fit, or contraction of the socket. Of all patients, 70.1% presented with changes that allowed acceptable fitting of the prosthesis with slight movement limitation and only 6 orbits (5.12%) had a good cavity for cosmetic appearance. Forty of 157 enucleated orbits did not receive radiation therapy at any moment (25.5%); 92.5% of them had a good fitting and in only 7.5% fitting problems due to postoperative complications were found. Early diagnosis, adequate treatment, and use of chemoreduction as initial therapy of intraocular retinoblastoma allow for an increased rate of preservation of the eye and reduce or eliminate the need for external beam therapy and its sequelae (AU)

Uncommon RB1 somatic mutations in a unilateral retinoblastoma patient

Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Somatic inactivation of both alleles of the RB1 tumor suppressor gene in a developing retina is a crucial event in the initiation of tumorigenesis in most cases of isolated unilateral retinoblastoma. We analyzed the DNA from tumor tissue and peripheral blood of a unilateral retinoblastoma patient to determine the RB1 mutation status and to provide an accurate genetic counseling. A comprehensive approach, based on our previous experience, was used to identify the causative RB1 mutations. Screening for RB1 mutations was performed by PCR direct sequencing, multiplex ligation-dependent probe amplification (MLPA) and Real Time-PCR analyses. Three different mutations were identified in the tumor DNA, which were absent in blood DNA. The somatic origin of these mutations was vital to rule out the heritable condition in this patient.

El retinoblastoma (RB) es el cáncer ocular más común de la niñez. La inactivación somática de ambos alelos del gen supresor de tumores RB1 en la retina en desarrollo es un evento crucial en la iniciación de la tumorigénesis en la mayoría de los casos de retinoblastoma unilateral. Nosotros analizamos el ADN de tumor y de sangre periférica de un paciente con retinoblastoma unilateral para identificar las mutaciones y así proveer un asesoramiento genético a la familia. Para ello utilizamos un protocolo basado en nuestra previa experiencia para identificar todas las mutaciones en el gen RB1 que causaron el RB. El rastreo de mutaciones se realizó por medio de los siguientes análisis: PCR-secuenciación, amplificación multiplex de sondas ligadas (MLPA) y PCR-Tiempo Real. Se encontraron tres mutaciones diferentes en el ADN del tumor, las cuales estaban ausentes en el ADN de la sangre. El origen somático de estas mutaciones es importante para indicar que la enfermedad no es hereditaria.

Managing the consequences of aggressive conservative treatment for refractory retinoblastoma with vitreous seeding / Lidando com as consequências do tratamento agressivo para retinoblastoma refratário com semeadura vítrea

A 4 year-old girl with bilateral, non-familial retinoblastoma (RB) was referred to our care after primary enucleation OS and active tumor OD refractory to multiple therapies (intravenous chemotherapy, laser/cryotherapy, and I-125 plaque radiotherapy). Vitreous seeding OD, initially controlled by several sessions of Ophthalmic Artery Infusion Chemotherapy (OAIC) and periocular chemotherapy, recurred shortly thereafter. The patient underwent intravitreal (IVit) Melphalan injections achieving tumor control despite the concurrent development of keratopathy, pupillary synechiae, cataract, and necrosis of the inferior fornix and the adjacent orbital fat, all secondary to the treatments administered. Repeated amniotic membrane implants and tarsorrhaphy were performed to alleviate the symptoms. Despite being tumor free for 6 months, a poor fundus view and treatment-related complications prompted us to consider enucleation, but parents declined. Following recent negative magnetic resonance imaging (MRI), her cataract was removed. She was then found to have tumor recurrence. Her eye was enucleated 12 months ago and she recovered well from the surgery. As ocular oncology embarks in eye-preserving treatments for retinoblastoma, it is important to address the cumulative effects and associated impact of such treatments and the possibility of failure.

Uma menina de 4 anos com retinoblastoma (RB) bilateral, não-familiar foi encaminhada após enucleação OE e tumor ativo OD refratário a múltiplas terapias (quimioterapia endovenosa, laser/crioterapia e braquiterapia com I-125). Semeadura vitrea OD, inicialmente controlada por inúmeras sessões de Quimioterapia Intra-Arterial Oftálmica (QIAO) e quimioterapia periocular, recorreu em seguida. Paciente recebeu injeções intravítreas de Melphalan obtendo controle tumoral apesar do desenvolvimento concomitante de ceratopatia, sinéquias pupilares, catarata, necrose do fórnice inferior e gordura periorbitária adjacente, todos secundários aos tratamentos usados. Implantes repetidos de membrana amniótica e tarsorrafias foram realizadas para melhora sintomatológica. Apesar de estar livre de tumor por 6 meses, a baixa visibilidade do fundo e complicações terapêuticas nos levaram a considerar enucleação que foi descartada pelos pais. Após recente ressonância magnética nuclear (RMN) negativa, a catarata foi removida. Foi então detectada recorrência tumoral. O olho foi enucleado há 12 meses e ela se recuperou bem da cirurgia. Enquanto a oncologia ocular embarca em tratamentos para preservar em retinoblastoma, é importante considerar os efeitos cumulativos e impacto associado desses tratamentos, e a possibilidade de fracasso.

Quistes retinianos maculares, fisiopatogenia e implicaciones. Reporte de serie de casos / Macular retinal cysts, physiopathogeny and implications. A case series report

Objetivo: reporte de casos que han presentado quistes retinianos maculares de fisiopatología traccional y con implicaciones ulteriores, sea hacia la involución espontánea o la progresión hacia agujero macular y su manejo. Métodos: estudio observacional descriptivo, tipo serie de casos, observados por retinólogos de una Institución Oftalmológica, estudiados en seguimiento y documentados con tomografía óptica coherente espectral. Resultados: fueron satisfactorios anatómica y funcionalmente según su evolución y manejo. Conclusiones: los quistes maculares traccionales pueden involucionar favorablemente o conducir a agujeros de manejo quirúrgico y pronóstico variable.

Purpose: to report cases presenting tractional macular cysts and subsequent implications either spontaneous involution or progression to macular holes and their management. Methods: retrospective study of case series observed by retinologists in a general ophthalmological institution, evaluated on follow-up and documented with spectral domain optical coherente tomography. Results: satisfactory, both anatomically and functionally according with evolution and management. Conclusions: tractional macular cysts may tend to a favorable spontaneous involution or progression to macular holes that require surgical management of variable prognosis.

Orbital retinoblastoma: case report / Retinoblastoma orbitário: relato de caso

We describe the case of a 9-month old boy with unilateral retinoblastoma and bulftalmo. Primary enucleation was the treatment of choice due to the lack of visual prognosis. The histology of the enucleated eye showed massive choroidal invasion by the tumor and the optic nerve free of neoplastic tissue. Therefore, no adjuvant chemotherapy or radiotherapy was indicated. Three months after the enucleation, the patient returned with massive orbital retinoblastoma with exposure of the conjunctiva. Treated with chemotherapy, the patient has been in remission for 12 months. The risk factors for orbital recurrence are discussed.

Relatamos paciente de 9 meses de idade com buftalmo e retinoblastoma unilateral. O paciente foi tratado com enucleação primária devido à falta de prognóstico visual. O exame do olho enucleado mostrou invasão maciça de coroide e ausência de comprometimento do nervo óptico não sendo, portanto, submetido a tratamento adjuvante de quimioterapia ou de radioterapia. Três meses após a enucleação, o paciente apresentou-se com retinoblastoma orbitário volumoso com exposição da conjuntiva. Tratado com quimioterapia permanece em remissão após 12 meses. São discutidos os fatores de risco para a ocorrência da recidiva orbitária.

Retinal vasoproliferative tumor / Tumor vasoproliferativo da retina

Retinal vasoproliferative tumor is a rare disease that has capillary hemangioma as the most frequent diferential diagnosis. The tumor is considered to be of reactive nature. It can be idiophatic or secondary to other ocular diseases such as: uveitis, retinitis pigmentosa, sickle cell disease, previous surgery and retinopathy of prematurity. Lesions with no exsudation or visual decrease can be observed. Lesions that need treatment can be managed by on or more modalities such as cryotherapy, a variety of lasers, surgical excision, radiation, and antiangiogenic intravitreal injections.

O tumor vasoproliferativo da retina é uma lesão rara, cujo principal diagnóstico diferencial é o hemangioma capilar da retina. O tumor tem natureza reacional. Pode ser idiopático ou secundário a outras doenças como: uveítes, retinose pigmentar, retinopatia da anemia falciforme, cirurgia prévia e retinopatia da prematuridade. Lesões sem exsudação ou baixa visual podem ser observadas. Quando há indicação de tratamento este pode ser feito pela crioterapia, vários tipos de lasers, excisão cirúrgica, radioterapia e injeções intravítrea de antiangiogênicos, isoladamente ou em associação.

Phacoemulsification and foldable acrylic IOL implantation in children with treated retinoblastoma / Facoemulsificação e implante de lente intraocular acrílica dobrável em crianças com retinoblastoma

PURPOSE: To study the results of cataract surgery in children with radiation-induced cataract after treatment for retinoblastoma. METHODS: Retrospective interventional case series. Six consecutive patients diagnosed with secondary cataracts due to radiation therapy for retinoblastoma. Intervention: Phacoemulsification and foldable acrylic intraocular lens implantation. Outcomes measu- red: Visual acuity, binocular indirect ophthalmoscopy and slit-lamp biomicroscopy. Aspirated lens material and aqueous humor samples were collected during surgery. RESULTS: Six uniocular children between 3 to 5 years of age at time of surgery were studied. The mean time interval between radiotherapy and cataract diagnosis was 22.3 months. The mean follow-up after surgery was 17.2 months (range: 12 to 23 months). All eyes achieved a clear visual axis after surgery allowing monitoring of the tumor status. None developed recurrence or retinoblastoma dissemination. Histopathological analysis of the aspired material showed no tumoral cells in all samples. All patients improved vision after cataract surgery. CONCLUSIONS: Phacoemulsification with acrylic intraocular lens implantation seems to be a safe, feasible, and effective method for the removal of radiation-induced cataracts in patients with treated retinoblastoma.

OBJETIVOS: Estudar os resultados da cirurgia da catarata induzida pela radioterapia para o tratamento do retinoblastoma em crianças. MÉTODOS: Estudo retrospectivo intervencional em série de casos onde seis pacientes consecutivos apresentaram catarata secundária à terapia por radiação para o retinoblastoma. Intervenção: Facoemulsificação e implante de lente intraocular acrílica dobrável. Foram avaliadas: acuidade visual, oftalmoscopia binocular indireta e biomicroscopia. Material para análise histológica do cristalino e do humor aquoso foi coletado durante as cirurgias. RESULTADOS: Seis crianças, entre 3 e 5 anos de idade, com catarata secundária à radiação para tratamento de retinoblastoma foram submetidas à cirurgia de facoemulsificação com implante de lente intraocular. A média do intervalo de tempo decorrido entre a radioterapia e o diagnóstico da catarata foi 22,3 meses. O período médio de seguimento após a cirurgia foi de 17,2 meses (intervalo: 12 a 23 meses). Todos os olhos melhoraram a visão e mantiveram eixo visual livre permitindo a fundoscopia para monitorar o tumor. Nenhum paciente evoluiu com recorrência ou disseminação do retinoblastoma. A análise histopatológica do material colhido resultou em ausência de células tumorais nas amostras. CONCLUSÕES: A cirurgia de facoemulsificação com implante de lente intraocular acrílica dobrável mostrou ser um procedimento seguro e efetivo para o tratamento da catarata induzida pela radioterapia em pacientes portadores de retinoblastoma.

Metástasis coroideas: clarinada hacia la nada: presentación de casos icónicos / Choroid metastasis: clarion call toward nothing: presentation of two iconic cases

La metástasis intraoculares de tumores sólidos o hematológicos, son un problema clínico para el oftalmólogo práctico y el oncólogo. La localización más frecuente es la coroides, constituyendo el tumor intraocular más frecuente. Suelen diagnósticarsé en pacientes en estadios tumorales muy avanzados, por lo que en el pasado la mayoría de las series publicadas eran descripciones de necropsias. Su diagnóstico generalmente puede hacerse mediante cuidadoso examen. Se estima que la frecuencia general en pacientes que fallecen por cáncer es de aproximadamente 12%, pero puede elevarse en 37% en aquellos con carcinoma mamario, muy superior a la de los tumores primarios, fundamentalmente los melanomas. No obstante, sin compresión ha aumentado en años recientes ofreciendose nuevas formas de tratamiento siendo todavía la radioterapia la que permite a los pacientes mantener una visión.

Intraocular metastases of solid and hematological tumors are clinical problem for the practicing ophthalmologist and oncologist. Its diagnosis can usually be made through careful examination. The most common intraocular tumor. They are often diagnosed in patients in very advanced tumor stages, which is why in the past most of the published series were descriptions of necropsies. The overall frequency of ocular metastases in patients dying of cancer is approximately 12%, but it can be as high as 37% in patients with breast cancer, highly superior to primary tumors, mainly melanomas. Hawever, our understanding of them has increased in recent years, offering new forms of treatment. Radiation therapy is still the cornerstone of treatment, allowing nost patients to maintain usefull vision. Clinical cases with photographic support of an iconic patient are presented to illustrate the problem.

Hemangioma racemoso da retina: um caso clínico / Retinal racemose hemangioma: case report

O Hemangioma racemoso da retina é uma malformação congênita caracterizada por comunicações arteriovenovas (AV) retinianas. Em cerca de 30 por cento dos casos pode haver manifestações a nível do sistema nervoso central (SNC), denominando-se então por Síndrome de Wyburn-Mason. Os autores apresentam um caso clínico de um doente do sexo masculino de 39 anos que recorre ao serviço de Urgência devido a diminuição da acuidade visual do olho esquerdo (OE) com cerca de seis dias de evolução.Apresenta melhor acuidade visual corrigida olho direito (OD): 4/10 e olho esquerdo (OE): 2/10.À fundoscopia apresenta disco óptico com limites indefinidos, alguma palidez, dilatação e tortuosidade, AV marcada bilateralmente. O hemangioma racemoso da retina é um diagnóstico clínico raro, efectuado por meio do exame oftalmológico. É importante verificar o envolvimento do SNC por meio da realização de angiorressonância magnética nuclear. Atualmente não existe nenhum tratamento preconizado, sendo importante a realização de observações periódicas para averiguação de eventuais complicações.

Racemose Haemangioma (RH) is a congenital anomaly, characterized by retinal arteriovenous(AV) malformation. About 30 percent of patients have signs of central nervous system (CNS) involvement, which has been called the Wyburn-Mason syndrome. The authors present a 39-year-old male patient, who was admitted at the emergency room with decreased visual acuity of his left eye, for the last 6 days. Ophthalmic examination was performed and showed a visual acuity of 4/10 in his right eye and of 2/10 in the left eye. Fundoscopy examination revealed pallor of both optic discs, with blurred limits and a characteristic dilation and AV connections. RH of retina is a rare entity which can be diagnosed by ophthalmic examination. Once this diagnosis is established, involvement of CNS has to be rulled out performing an angioMRI. Currently, no specific treatment has been defined, except a periodic follow-up to prevent complications.