Importancia del diagnóstico por imágenes multimodales en glaucoma agudo de ángulo cerrado: reporte de caso / Importance of multimodal imaging diagnostics in acute angle closure glaucoma: Case report

Describir la historia natural y el manejo de un glaucoma de cierre angular agudo secundario a melanoma coroideo.Mujer de 70 años que presenta dolor agudo con presión intraocular elevada y catarata madura y que fue diagnosticada de glaucoma agudo de ángulo cerrado en el ojo derecho. Mediante estudios adicionales de diagnóstico por imagen se descubrió un melanoma coroideo que causaba el cierre agudo del ángulo. Se realizó enucleación, y actualmente la paciente se encuentra en estrecha vigilancia postoperatoria por parte de oftalmología y oncología.Este caso refleja la importancia del diagnóstico y el tratamiento precoz de los tumores intraoculares en la disminución de la incidencia de metástasis y el aumento de la supervivencia. En el glaucoma de ángulo cerrado agudo secundario, el tratamiento debe estar dirigido a resolver el factor desencadenante del glaucoma. (AU)

To describe the natural history and management of an acute angle closure secondary to choroidal melanoma.A 70-year-old female presented with pain, elevated intraocular pressure, mature cataract, and angle closure in right eye. With further studies she was found to have a choroidal melanoma causing the acute angle closure. Enucleation was performed and the patient is currently in close postoperative surveillance by ophthalmology and oncology.The importance of early identification and treatment of intraocular tumors to decrease incidence of metastasis. In secondary acute angle-closure glaucoma treatment should be targeted towards resolving the triggering factor of glaucoma. (AU)

Importance of multimodal imaging diagnostics in acute angle closure glaucoma: Case report.

To describe the natural history and management of an acute angle closure secondary to choroidal melanoma. A 70-year-old female presented with pain, elevated intraocular pressure, mature cataract, and angle closure in right eye. With further studies she was found to have a choroidal melanoma causing the acute angle closure. Enucleation was performed and the patient is currently in close postoperative surveillance by ophthalmology and oncology. The importance of early identification and treatment of intraocular tumors to decrease incidence of metastasis. In secondary acute angle-closure glaucoma treatment should be targeted towards resolving the triggering factor of glaucoma.

Impacto del COVID-19 en una enfermedad rara (melanoma uveal) en una unidad de referencia nacional de tumores intraoculares en España / Impact of COVID-19 on a rare disease (uveal melanoma) in a national reference unit of intraocular tumors in Spain

Objetivo Analizar el impacto de la pandemia por COVID-19 en el diagnóstico y manejo del melanoma uveal (tumor incluido en el catálogo de enfermedades raras por Orphanet), en una unidad de referencia nacional española de tumores intraoculares, durante el primer año de pandemia. Materiales y métodos Se realizó un estudio retrospectivo observacional de pacientes con melanoma uveal en la Unidad de Referencia Nacional de Tumores Intraoculares del Adulto del Hospital Clínico Universitario de Valladolid (España), analizando los periodos pre- y pos-COVID-19: del 15 de marzo de 2019 al 15 de marzo de 2020 y del 16 marzo de 2020 al 16 de marzo de 2021. Se recogieron datos demográficos, demora diagnóstica, tamaño del tumor, extensión extraocular, tratamiento y evolución. Se utilizó un modelo de regresión logística multivariable para identificar los factores que se asociaron a la variable: enucleación. Resultados Se incluyeron 82 pacientes con melanoma uveal, de los cuales 42(51,21%) pertenecían al periodo pre-COVID-19 y 40(40,78%) al periodo pos-COVID-19. Se observó un aumento del tamaño tumoral al diagnóstico y del número de enucleaciones durante el periodo pos-COVID-19 (p<0,05). La regresión logística multivariable demostró que tanto el tamaño tumoral mediano-grande como los pacientes diagnosticados en el periodo pos-COVID-19 estaban relacionados de forma independiente con un riesgo mayor de enucleación (OR 250, IC95%, 27,69-2256,37; p<0,01 y OR 10; IC95%,1,10-90,25; p=0,04, respectivamente). Conclusiones El incremento del tamaño tumoral observado en los melanomas uveales diagnosticados durante el primer año de pandemia por COVID-19 pudo favorecer el aumento de las enucleaciones realizadas en dicho periodo (AU)

Objective To analyze the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumor included in the Orphanet catalog of rare diseases) in a Spanish national reference unit for intraocular tumors during the first year of the pandemic. Material and methods An observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analyzing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumor size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. Results Eighty-two patients with uveal melanoma were included, of which 42(51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumor size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p<0.05). Multivariable logistic regression demonstrated that both medium-large tumor size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p<0.01 and OR 10; 95% CI,1.10-90.25; p=0.04, respectively). Conclusions The increase in tumor size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period (AU)

Impact of COVID-19 on a rare disease (uveal melanoma) in a national reference unit of intraocular tumors in Spain.

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumour included in the Orphanet catalogue of rare diseases) in a Spanish national reference unit for intraocular tumours during the first year of the pandemic. METHOD: An observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analysing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumour size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. RESULTS: Eighty-two patients with uveal melanoma were included, of which 42 (51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumour size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p < 0.05). Multivariable logistic regression demonstrated that both medium-large tumour size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p < 0.01 and OR 10; 95%CI, 1.10-90.25; p = 0.04, respectively). CONCLUSIONS: The increase in tumour size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

Metastasis of Uveal Melanoma in Bladder: Presentation of Two Cases and Review of the Literature

Objective: Secondary urinary bladder tumors account for 2% of neoplasms in this location. Melanoma is the neoplasm that mostfrequently produces distant metastases in the bladder. Despite its low prevalence, it should be a possible diagnosis to considerfacing urological symptoms, due to the existence of targeted therapies. Method: We present two cases of uveal melanoma metastasis in the bladder, their characteristics, and a review of the literature. Result: In this paper we present the histological characteristics and complementary techniques for the diagnosis of bladder metastases of melanoma and propose their inclusion among the possible differential diagnoses for bladder neoplasms. Conclusions: Given that there are currently targeted therapies against melanoma, the relevance of their inclusion in the differential diagnosis of bladder tumors stands out. (AU)

Objetivo: La vejiga urinaria no es un órgano frecuente de metastasis a distancia. Sin embargo, se puedever afectada secundariamente en un 2% de todas las neoplasias. Dicha afectación se produce habitualmente por extensión local de otros tumores, aunque, ciertas neoplasias pueden producir metástasis a distancia en la vejiga, como es el caso del melanoma. A pesar de esta baja prevalencia, los antecedentes personales del paciente deben ser tenido sen cuenta en el diagnóstico de la neoplasia vesical. Método: Se presentan dos casos de metástasis de melanoma uveal en vejiga, sus características y una revisiónde la literatura.Resultado: En este trabajo se exponen las características histológicas y las técnicas complementarias para el diagnóstico de las metástasis de melanoma y se resalta su importancia en el diagnóstico de las neoplasias vesicales. Conclusiones: Dado que actualmente existen terapiasdirigidas frente al melanoma, se destaca la relevancia de suinclusión en el diagnóstico diferencial de los tumores de lavejiga. (AU)

Melphalan intra-arterial chemotherapy for choroidal melanoma chemoreduction.

BACKGROUND: Intra-arterial chemotherapy (IAC) has been used to treat multiple cancers including liver metastasis from uveal and cutaneous melanoma but not as primary tumor treatment. We report the compassionate use of chemoreduction with intra-arterial melphalan before ruthenium brachytherapy to salvage an eye with choroidal melanoma. CASE PRESENTATION: A 61-year-old female patient complained of decreased vision and central-temporal scotoma in OS (left eye) for 1 month. Visual acuity was 20/20 in right eye (OD) and 20/125 OS. Anterior segment examination and intraocular pressure were unremarkable in both eyes, as was fundus examination of the OD. Fundus examination of OS revealed a brown, solid tumor partially obscuring the temporal optic disc margin and extending to the equatorial fundus midzone. Serous retinal detachment was present over the lesion and around it. Ultrasonography revealed a solid choroidal tumor with a largest basal diameter (LBD) of 13.0 mm and thickness of 10.4 mm. The tumor presented acoustic hollowness and a superimposing retinal detachment. After metastatic screening was negative, the patient underwent intra-arterial chemotherapy with melphalan. Three weeks later, her visual acuity was 20/200 and there was noticeable tumor regression to 11.9 mm (LBD) by 7.9 mm (thickness) allowing brachytherapy to be performed. Ten weeks after brachytherapy (13 weeks after IAC), visual acuity was HM due to biopsy-related vitreous hemorrhage (VH). Tumor dimensions were 9.9 (LBD) mm and 6.5 mm (thickness) and PPV was performed to remove VH. Six weeks after PPV (20 weeks after IAC), her visual acuity was 20/200 and further reduction of tumor dimensions was observed: largest basal diameter was 8.9 mm and thickness was 4.9 mm. CONCLUSION: This case illustrates the feasibility of combining induction IAC prior to ruthenium brachytherapy for large choroidal melanoma. More studies are warranted to confirm these early preliminary findings.

Estudio epidemiológico y anatomopatológico del melanoma uveal / Epidemiologic and anatomopathologic study of uveal melanoma

Objetivo: Determinar el comportamiento epidemiológico y anatomopatológico del melanoma uveal. Método: Estudio descriptivo, longitudinal y retrospectivo en pacientes enucleados por diagnóstico de melanoma uveal en el Centro Oftalmológico de Villa Clara entre enero de 2010 a mayo de 2021. Resultados: La edad media de presentación del melanoma uveal fue de 61,3 años. Las mujeres fueron ligeramente más afectadas que los hombres-56,3 por ciento. El 81,3 por ciento de los melanomas uveales se originó en la coroide. Los tumores de células epitelioides y fusiformes fueron los más representativos; ambos con un 37,5 por ciento. El grosor y diámetro basal medio en los tumores estudiados fue de 11,2 mm y 15,8 mm respectivamente; prevalecieron los tumores medianos con un 56,3 por ciento. Se encontró infiltración tumoral en 37,5 por ciento de los ojos, la infiltración escleral fue la más frecuente. Conclusiones: El melanoma uveal se presenta con mayor frecuencia en personas con edad avanzada y en la coroide. El estudio histológico confirma el diagnóstico en la totalidad de los casos. Aproximadamente 2/3 de los tumores con algún grado de infiltración son grandes y la mitad de células epitelioides(AU)

Objective: To determine the epidemiologic and anatomopathologic behavior of uveal melanoma. Methods: Descriptive, longitudinal and retrospective study in patients enucleated for diagnosis of uveal melanoma in the Ophthalmologic Center of Villa Clara from January 2010 to May 2021. Results: The average age of presentation of uveal melanoma was 61.3 years. Women were slightly more affected than men-56.3 percent. 81.3 percent of uveal melanomas originated in the choroid. Epithelioid and spindle cell tumors were the most representative; both with 37.5 percent. The average thickness and basal diameter of the tumors studied were 11.2mm and 15.8mm respectively; medium-sized tumors prevailed with 56.3 percent. Tumor infiltration was found in 37.5 percent of the eyes, scleral infiltration was the most frequent. Conclusions: Uveal melanoma occurs more frequently in people with advanced age and in the choroid. Histological study confirms the diagnosis in all cases. Approximately 2/3 of the tumors with some degree of infiltration are large and half are epithelioid cells(AU)

Melanoma del cuerpo ciliar en un adulto joven: reporte de caso / Ciliary body melanoma in a young adult: a case report

Resumen Reporte de un caso: Femenino de 29 años de edad sin comorbilidades, con baja visual progresiva en ojo derecho de 1 mes de evolución. A la exploración oftalmológica agudeza visual de ese ojo en 20/80, conjuntiva bulbar superior con vaso centinela, masa retroiridiana color naranja vascularizada que subluxa el cristalino hacia inferior. Por ultrabiomicroscopía se evidencia una masa en domo dependiente del cuerpo ciliar de 4.87x5.74mm con reflectividad interna media y regular. Se realiza primeramente BAAF reportando melanoma, después se hace enucleación con resultado histopatológico de melanoma amelanótico. Posterior, se realiza implante de prótesis cosmética y se encuentra en seguimiento por oncología sin presentar datos de actividad tumoral después de 4 años. Discusión: Los melanomas uveales son la causa más común de tumores malignos intraoculares primarios en adultos, localizados principalmente en coroides (90%), siendo extremadamente rara su aparición en el cuerpo ciliar (6%) e iris (4%). El abordaje de un tumor del cuerpo ciliar debe incluir una anamnesis y exploración física completa con estudios paraclínicos adecuados para poder discernir entre los diagnósticos diferenciales. El ultrasonido ocular es el estudio auxiliar más importante ya que brinda características típicas propias del tumor. El tratamiento continúa basado en el COMS con un pronóstico sombrío. Los factores de mal pronóstico son presencia de metástasis, tamaño del tumor, extensión extraocular y estirpe epitelioide. Limitaciones: No se contaban con todas las alternativas de tratamiento. Originalidad: Caso inusual en pacientes jóvenes y por su sitio.

Abstract: Case report: 29-year-old female with no comorbidities, with progressive vision loss in the right eye of 1 month's evolution. On ophthalmological examination, visual acuity was 20/80, superior bulbar conjunctiva with sentinel vessel, vascularised orange retroiridian mass generating a lens subluxation inferiorly. Ultrabiomicroscopy revealed a dome-shaped mass dependent on the ciliary body measuring 4.87x5.74mm with medium and regular internal reflectivity. A FNA was done and melanoma was reported, then enucleation was performed with histopathological findings of amelanotic melanoma. Subsequently, a cosmetic prosthesis was implanted and the patient has been followed up by oncology with no evidence of tumour activity after 4 years. Discussion: Uveal melanomas are the most common cause of primary intraocular malignant tumours in adults, mainly located in the choroid (90%), being extremely rare in the ciliary body (6%) and iris (4%). The approach to a ciliary body tumour should include a complete anamnesis and physical examination with appropriate paraclinical studies to be able to discern between differential diagnoses. Ocular ultrasound is the most important ancillary study as it provides typical features of the tumour. Treatment is still based on COMS and the prognosis remains poor. Poor prognostic factors are the presence of metastases, tumour size, extraocular extension and epithelioid lineage. Limitations: Not all treatment alternatives were available. Originality: Unusual case in young patients and because of its site.

Identification of extraocular extension in uveal melanoma by ophthalmological ultrasound.

BACKGROUND AND PURPOSE: Uveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound. MATERIAL AND METHODS: A descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study. RESULTS: Ten patients with an average age of 72.3 years were included. The largest proportion of them were medium-sized tumours, followed by large and small ones. The most frequent morphology of the primary tumour was cupuliform. All the EE presented lower internal reflectivity compared to the primary tumour. No trans-scleral connection bridges were found between the primary tumour and the EE in the ultrasound studies. 50% of patients underwent primary enucleation at the time of diagnosis of intraocular MU due to the presence of the EE, and the remaining 50% presented the EE after initial treatment of the primary tumour with I125 brachytherapy. Sixty percent of the patients presented with posterior EE, and were therefore diagnosed with ultrasound A and B. The most frequent histopathological pattern with 87.5% of patients was the epithelioid pattern. DISCUSSION: Ultrasound scanning in patients with MU is mandatory for diagnosis and follow-up of EE. BMU and A and B ultrasound are the test of choice for anterior and posterior EE, respectively. EE have particular ultrasound characteristics such as low internal reflectivity, regularity of their contour and their location usually adjacent to the base of the primary intraocular tumor.

Identificación de extensión extraocular en el melanoma uveal mediante ecografía oftalmológica / Identification of Extraocular Extension in Uveal Melanoma by Ophthalmological Ultrasound

Antecedentes y objetivoEl melanoma uveal es el tumor primario maligno intraocular más frecuente en la población adulta, con una tasa de supervivencia del 50% a pesar de los avances en el tratamiento y conocimiento de esta enfermedad. La presencia de extensión extraocular (EE) empeora el pronóstico de estos pacientes, por lo que su correcta identificación puede asegurar su manejo e intervención temprana. La ecografía oftalmológica es la técnica de elección para el diagnóstico y seguimiento de estos pacientes, tanto de la EE anterior mediante biomicroscopía ultrasónica (UBM), como de la EE posterior mediante ecografía A y B. El objetivo de este estudio es describir las características ecográficas de la UBM y de la ecografía A y B.Material y métodosSe realiza un estudio descriptivo y retrospectivo de los pacientes diagnosticados de melanoma uveal (UM) y EE desde 2003 hasta 2019. Las características ecográficas de la enfermedad local y el seguimiento luego del tratamiento se registraron de maneracompleta y en cada visita. En caso de EE anteriores se realizaron fotografías de segmento anterior y BMU, por el contrario las que involucran el segmento posterior se exploraron bajo ecografía modo A y B. Todos los ojos enucleados se enviaron para su estudio anatomopatológico.

Background and purposeUveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound.Material and methodsA descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study.

Uveal melanoma in a canine: a case report / Melanoma uveal en un canino: un reporte de caso / Melanoma uveal em um canino: um relato de caso

Abstract In this report we present the clinical case of a Harlequin Great Dane male canine, which presented the opaque and very red right eye. In the ophthalmological examination he presented an acute picture of uveitis, followed by glaucoma and visual deficit, and does not report physical trauma or a blunt force at eye level. The definitive diagnosis was uveal melanoma, confirmed by ultrasound, cytology and histopathology.

Resumen En el presente reporte se expone el caso clínico de un canino macho Gran Danés Arlequín, el cual, presentó el ojo derecho opaco y muy rojo. En el examen oftalmológico presentó un cuadro agudo de uveitis, seguido por glaucoma y déficit visual; no reporta trauma físico o algún golpe contundente a nivel ocular. El diagnóstico definitivo fue melanoma uveal, confirmado por ecografía, citología e histopatología.

Resumo No presente relato, apresenta-se o caso clínico de um canino macho Great Dane Harlequin, que apresentava o olho direito opaco e muito vermelho. No exame oftalmológico, apresentava quadro agudo de uveíte, seguido de glaucoma e déficit visual; não relata trauma físico ou força bruta no nível dos olhos. O diagnóstico definitivo foi o melanoma uveal, confirmado por ultrassonografia, citologia e histopatologia.

Clinical and histopathological features of choroidal melanoma-related enucleated eyes in a Spanish tertiary hospital. / Características clínicas e histopatológicas de ojos enucleados por melanoma uveal en un hospital terciario en España.

OBJECTIVE: To study clinical and pathological variables leading to a poor prognosis in a sample of uveal malignant melanoma patients who required eyeball enucleation as final treatment approach. All patients were seen and treated in the same public tertiary hospital in Madrid (Spain) within a 6-year time-period. MATERIALS AND METHODS: Longitudinal observational retrospective study. The presence of clinical and pathologic factors known to be linked to poor prognosis, as well as other features, was assessed in 30 malignant melanoma: 20 de novo-enucleated malignant melanoma eyes (group A), and 10 in eyes that received radiotherapy prior to enucleation (group B). The diagnostic reliability of magnetic resonance imaging was assessed by comparing it with the histology results (gold standard) as a means to detect scleral and extra-scleral extension. RESULTS: Tumour size, Bruch's membrane rupture, scleral infiltration, and distance to the optic nerve were the most decisive factors for a poor prognosis in the study sample. In 93% of cases the condition was under control, with a 6% incidence rate of metastatic spread and a 100% rate of overall survival for a mean follow-up period of 3±1.5 (range 1.2-6) years. In the study population, the sensitivity of the magnetic resonance imaging to detect scleral infiltration was 27%, which increased to 100% for identifying extra-scleral involvement. CONCLUSIONS: The analyses of the clinical and pathological data collected within the framework of this study justify enucleation as the treatment of choice for the patients of this study. Magnetic resonance imaging was not found to be an optimum screening method to detect scleral infiltration in this study sample.

Effects of ranibizumab and amfenac on the functional abilities and radiosensitivity of uveal melanoma cells / Efeitos do ranibizumabe e do amfenac nas habilidades funcionais e na radiossensibilidade de células de melanoma uveal

ABSTRACT Purpose: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy. Methods: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy). Results: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls. Conclusion: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.

RESUMO Objetivo: Avaliar os efeitos do ranibizumabe em associação com o amfenac nas células de melanoma uveal humano e explorar a capacidade desses compostos em sensibilizar as células de melanoma uveal à radioterapia. Métodos: Células de melanoma uveal humano do tipo 92.1 foram cultivadas e submetidas ao tratamento proposto (ranibizumabe, amfenac e a combinação de ambos). Ensaios de proliferação, migração e invasão com as células de melanoma uveal do tipo 92.1 foram avaliados após tratamento com ranibizumabe (125 mg/ml), amfenac (150 nM) e a combinação de ambos. Além disso, as taxas de proliferação foram avaliadas após tratamento com ranibizumabe e amfenac com subsequente exposição das células a diferentes doses de radiação (0 Gy, 4 Gy e 8 Gy). Resultados: Ensaio de proliferação: células tratadas com ranibizumabe e amfenac combinados apresentaram taxas de proliferação inferiores em comparação ao grupo controle (p=0,016), do que as tratadas apenas com ranibizumabe (p=0,033). Ensaio de migração: foi observada uma taxa de migração significativamente mais baixa nas células tratadas com amfenac do que no grupo controle (p=0,014) e do que nas tratadas com ranibizumabe (p=0,044). Ensaio de invasão: não houve diferenças significativas entre os grupos estudados. Exposição à irradiação: no grupo da dose de 4 Gy, não houve diferença significante entre os grupos. No grupo da dose de 8 Gy, o tratamento com ranibizumabe, afenac e sua combinação antes da aplicação da radiação de 8 Gy levou a uma redução acentuada nas taxas de proliferação (p=0,009, p=0,01 e p=0,034, respectivamente) em comparação aos grupos controle. Conclusão: A combinação de ranibizumabe e amfenac reduziu a taxa de proliferação das células de melanoma uveal; no entanto, apenas o amfenac diminuiu significativamente a migração celular. A radiossensibilidade das células de melanoma uveal do tipo 92.1 aumentou após a administração de ranibizumabe, amfenac e sua combinação. Mais investigações são necessárias para determinar se esta é uma estratégia de pré-tratamento viável para tornar grandes tumores passíveis de radioterapia.

Amelanotic iris melanoma in a 7 year-old hispanic boy with subclinical globe perforation. / Melanoma amelanótico del iris en un niño hispano de 7 años con perforación del globo subclínica.

We report an unusual case of an amelanotic melanoma in a 7 year old hispanic child with subclinical globe perforation. Uveal melanoma rarely occurs in children. Young affected patients are mostly light-colored eye Caucasian adolescents. Since they are not common, these tumors are usually not recognized and misdiagnosed. Differential diagnoses and therapeutic options are outlined.

Ultrasound, histopathological, and genetic features of uveal melanoma in a Mexican-Mestizo population. / Características ultrasonográficas, histopatológicas y genéticas del melanoma uveal en población mexicana mestiza☆.

OBJECTIVE: To describe the ultrasound, histopathological and genetic characteristics of uveal melanoma in a Mexican-Mestizo population. MATERIAL AND METHODS: A total of 39 enucleated eyes with a histopathological diagnosis of uveal melanoma were assessed by describing the clinical findings, and ultrasound, histopathological and genetic features. RESULTS: A high correlation was observed between tumour height measurement using ultrasound and histopathology. In our cases, tumour size and reflectivity were higher compared with those reported in the literature. The preliminary data on the molecular assessment of the tumours show the presence of an unreported polymorphism (T>C IVS5+34) and one sample with GNAQ mutation (A>C CAA>CCA Gln 209 Pro). CONCLUSION: Ultrasound is a reliable method to identify the size of the tumour. Furthermore, knowledge of the molecular mechanisms promises new perspectives for the development of new targeted therapeutics. Fortunately this leads to progress in the treatment of patients with metastatic disease or prevents it in those at high risk.

Melanoma maligno de coroides: a propósito de un caso / Choroidal malignant melanoma: a case report

El melanoma maligno de coroides es el tumor intraocular primario más frecuente en la edad adulta. Su evolución clínica es muy variable y constituye un peligro potencial para la vida de las personas afectadas. Se presenta el caso de un paciente de 42 años, caucásico, de procedencia urbana que acudió al Centro Oftalmológico de Holguín por disminución lenta y progresiva de la visión de aproximadamente hacía dos años de evolución que inicialmente comenzó como un defecto del campo visual periférico hasta afectar la visión central. La oftalmoscopía mostró lesión tumoral yuxtapapilar de coloración pardo-grisácea, elevada en forma de hongo, que produjo desprendimiento de retina secundario en tienda de campaña. Fue diagnosticado como portador de un melanoma maligno de coroides y remitido al Instituto Nacional de Oncología y Radiobiología donde se le realizó la enucleación del ojo derecho y se confirmó el diagnóstico por anatomía patológica. Se discutieron los principales factores de riesgo, la forma clínica de presentación, los hallazgos en las investigaciones clínicas realizadas para el diagnóstico, la modalidad de tratamiento aplicada, la evolución y el pronóstico, a partir de la información recogida de la revisión del expediente clínico del paciente.(AU)

Choroidal malignant melanoma is the most frequent intraocular tumor in adults. Its clinical evolution is very variable and it is a potential hazard for the life of the affected people. The case of a 42-year-old Caucasian urban male patient is reported. The patient presented to the Ophthalmological Center of Holguín complaining of slow and progressive loss of vision of about 2-years´ evolution that initially began as a peripheral visual field defect up to affect central vision. The ophthalmoscopy showed an elevated grayish-brown-colored mushroom-shaped tumoral lesion next to the papilla that produced a secondary tent-like retinal detachment. He was diagnosed as carrier of choroidal malignant melanoma and was referred to The National Institute of Oncology and Radiobiology where the enucleation of his righ eye ball was performed and the diagnosis was confirmed through pathological study. The main risk factors, clinical presentation, clinical research findings for diagnosis, treatment, evolution and prognosis were discussed from the information obtained from his clinical record.

Melanoma maligno de coroides: a propósito de un caso / Choroidal malignant melanoma: a case report

El melanoma maligno de coroides es el tumor intraocular primario más frecuente en la edad adulta. Su evolución clínica es muy variable y constituye un peligro potencial para la vida de las personas afectadas. Se presenta el caso de un paciente de 42 años, caucásico, de procedencia urbana que acudió al Centro Oftalmológico de Holguín por disminución lenta y progresiva de la visión de aproximadamente hacía dos años de evolución que inicialmente comenzó como un defecto del campo visual periférico hasta afectar la visión central. La oftalmoscopía mostró lesión tumoral yuxtapapilar de coloración pardo-grisácea, elevada en forma de hongo, que produjo desprendimiento de retina secundario en tienda de campaña. Fue diagnosticado como portador de un melanoma maligno de coroides y remitido al Instituto Nacional de Oncología y Radiobiología donde se le realizó la enucleación del ojo derecho y se confirmó el diagnóstico por anatomía patológica. Se discutieron los principales factores de riesgo, la forma clínica de presentación, los hallazgos en las investigaciones clínicas realizadas para el diagnóstico, la modalidad de tratamiento aplicada, la evolución y el pronóstico, a partir de la información recogida de la revisión del expediente clínico del paciente.

Choroidal malignant melanoma is the most frequent intraocular tumor in adults. Its clinical evolution is very variable and it is a potential hazard for the life of the affected people. The case of a 42-year-old Caucasian urban male patient is reported. The patient presented to the Ophthalmological Center of Holguín complaining of slow and progressive loss of vision of about 2-years´ evolution that initially began as a peripheral visual field defect up to affect central vision. The ophthalmoscopy showed an elevated grayish-brown-colored mushroom-shaped tumoral lesion next to the papilla that produced a secondary tent-like retinal detachment. He was diagnosed as carrier of choroidal malignant melanoma and was referred to The National Institute of Oncology and Radiobiology where the enucleation of his righ eye ball was performed and the diagnosis was confirmed through pathological study. The main risk factors, clinical presentation, clinical research findings for diagnosis, treatment, evolution and prognosis were discussed from the information obtained from his clinical record.

[Iris mammillations. Three case reports]. / Mamelones de iris. A propósito de tres casos.

CLINICAL CASES: We report the cases of 3 young patients who were seen in our hospital with the diagnosis of iris mammillations. Two of them were bilateral without familial association. The third child had iris mammillations as part of an ocular melanocytosis. None of them had abnormalities in the posterior segment or the pachymetry. DISCUSSION: The discovery of iris mammillations during an examination requires a long term follow up of these patients due to its association with uveal melanoma. This is required whether it is a casual discovery or in the presence of ocular melanocytosis.

[Uveal melanoma: clinical characteristics, treatment and survival in a series of 500 patients]. / Melanoma uveal: características clínicas, tratamiento y supervivencia en una serie de 500 pacientes.

OBJECTIVE: To analyse the clinical features, treatment and survival of uveal melanoma patients diagnosed in a referral Intraocular Tumours Unit over a twenty-year period. METHODOLOGY: A prospective study was performed including five hundred patients, diagnosed between January 1992 and December 2011. Clinical tumour characteristics and treatment were collected in a database in Microsoft@ Access@. The numeric variables were expressed as means of frequency and standard deviation, and the quantitative variables using frequency tables. RESULTS: The mean age of the sample was 62.19 years, with 51.2% females, and 64.2% presented with symptoms. The tumours were small in 31.12% of cases, and large in 23.09%, according to COMS criteria. Hazel green was the iris colour in 42.2% of the cases. The initial treatment was episcleral brachytherapy in 42.4% of the total. The overall mortality rate was 17% and 31.3%, and melanoma-related mortality rate was 11.6% and 14.8%, at 5 and 10 years, respectively. CONCLUSIONS: In the serie studied melanomas were more frequent in women, and a higher proportion of darker irides were observed than in other previous studies. Most of the tumours were diagnosed when they became symptomatic and in the early or medium stages, allowing conservative therapies to be used, with brachytherapy being the predominant treatment. The melanoma-related mortality appeared to be lower than previously data published. However, further studies are required on the factors influencing survival.