Beneath the surface: a case report of metastatic iridociliary ring melanoma treated with pembrolizumab / Abaixo da superfície: relato de caso de melanoma metastático iridociliar em anel tratado com pembrolizumabe

ABSTRACT Iridociliary ring melanoma is an uncommon type of uveal melanoma. Clinical manifestation varies from asymptomatic cases to masquerade syndromes mimicking refractory glaucoma. Treatment options include radiotherapy and enucleation. Management of metastatic uveal melanoma remains discouraging. Novel therapies using immune checkpoint inhibitors are currently under study. We present a case of a 54-year-old Hispanic woman with progressive vision loss due to metastatic ring melanoma with anterior chamber seeding treated with pembrolizumab.

RESUMO O melanoma iridociliar em anel é um tipo incomum de melanoma uveal. As manifestações clínicas variam desde casos assintomáticos até síndromes mascaradas que mimetizam um glaucoma refratário. As opções de tratamento incluem radioterapia e enucleação. O manejo do melanoma uveal metastático continua desanimador. Novas terapias usando inibidores de checkpoint imunológico estão atualmente em estudo. Apresentamos o caso de uma mulher hispânica de 54 anos com perda progressiva da visão por um melanoma metastático em anel, com semeadura de câmara anterior, tratada com pembrolizumabe.

Research advances on anti-vascular endothelial growth factor in the treatment of intraocular tumors and its complications / 中华眼底病杂志

Intraocular tumors is a serious blinding eye disease, which has a serious impact on patients' vision and even life. At present, the main treatments include surgical treatment, radiation therapy, chemotherapy, laser therapy and combination therapy. In recent years, with the wide application of anti-vascular endothelial growth factor (VEGF) in the treatment of ocular diseases, many studies have confirmed that anti-VEGF drugs play an important auxiliary role in the treatment of intraocular tumors and its complications. In terms of the therapeutic effect, intravitreal anti-VEGF combined with other methods have a good prognosis in the treatment of choroidal metastatic carcinoma and retinoblastoma, while the therapeutic effect of uveal melanoma is still controversial. In the treatment of intraocular tumor complications, intravitreal anti-VEGF also has a good effect on the secondary lesions of choroidal osteoma and radiation retinopathy. As for drug safety, intravitreal anti-VEGF can significantly reduce the toxic and side effects of systemic chemotherapeutic therapy. However, the dosage and medication regimen of anti-VEGF drugs in the treatment of intraocular tumors and their complications have not been unified in current studies, and further basic and clinical trials are still needed to explore in the future.

Research progress of single-cell transcriptome sequencing in uveal melanoma / 中华眼底病杂志

Uveal melanoma (UM) is an aggressive and lethal tumor in the eye. The complexity and heterogeneity of UM and its microenvironment leads to a lack of strategies for early prevention and treatment of metastases. Single-cell sequencing technologies provide critical insights into deciphering the complexity of intratumor heterogeneity and the microenvironment by enabling genomic, transcriptomic, and epigenetic analysis at the single-cell level. With the help of bioinformatics analysis combined with artificial intelligence algorithms, molecular indicator systems related to prognosis as well as therapeutic targets can be found, which can provide a basis for guiding the selection of clinical treatment plans. However, the single-cell sequencing technology also has certain limitations, such as high sample requirements, expensive and time-consuming sequencing. It is believed that with the improvement of science and technology and the update of analytical methods, these shortcomings can be gradually solved, and this rare tumor will eventually be overcome in the future, and the goal of long-term survival of UM patients will be achieved.

Clinical research status and progress of uveal melanoma in China of 2011-2021 / 中华眼底病杂志

Uveal melanoma (UM) is one of the most common primary intraocular malignancy in adults. The incidence of UM is lower in Asia than in Europe and the United States, however, the age of onset of UM patients in Asia is earlier than in the European and American populations. With the improvement of economic living standards in recent years, UM as a rare intraocular tumor has been gradually recognized by the public. In the past 10 years, the research of UM in China has been characterized by a large number and rapid development. Among them, the direction of molecular genetics represented by non-coding RNA, the frontier development of potential anticancer drugs for UM and Chinese traditional medicines are the research hotspots for scholars in China. In the past 10 years, China has made a relatively complete understanding and research progress on the pathogenesis, diagnosis and treatment of UM. On the other hand, compared with European and American countries, China still lacks in frontier research such as immunotherapy. With the further efforts of Chinese ophthalmology researchers and research teams, and with the further development of scientific research in my country, it is believed that the mechanism affecting tumors can be further elucidated, providing more possibilities for treatment and improving the prognosis of UM patients in China.

Response patterns and treatment outcomes of uveal melanoma patients treated with external scleral plaque radiotherapy / 中华眼底病杂志

Objective:To observe the different clinical response patterns of uveal melanoma (UM) patients after external scleral plaque radiotherapy (PRT), and to investigate the risk factors of secondary enucleation after treatment failure.Methods:A single-centre retrospective study. Demographic baseline characteristics and clinical data were collected from 465 UM patients treated with 125I external scleral PRT at Beijing Tongren Hospital from March 2011 to September 2017. Among them, 217 were male and 248 were female, tumor all occurred monocularly. The mean age of subjects was 46.7±12.1 years. Reasons for secondary enucleation included local tumor treatment failure, glaucoma, scleral necrosis and patient request. Tumor grading was based on the grading standards established by the American Joint Committee on Cancer (AJCC). The pattern of tumor response after PRT was classified as degenerated type, growth type, stable type or other types according to literature criteria. The median follow-up time after PRT was 59 months to observe tumor changes. Complete follow-up records of 3 or more color doppler ultrasound imaging (CDI) was available in 245 cases. A t-test was performed to compare the patient's age, intraocular pressure, best corrected visual acuity, tumor thickness and maximum basal diameter before treatment; a chi-square test was performed to compare the patient's gender, AJCC T classification of the tumor, whether the ciliary body was involved, presence of subretinal fluid, optic disc invasion and vitreous hemorrhage, tumor shape and location. Kaplan-Meier survival analysis was used to estimate the cumulative probability of secondary enucleation after extra-scleral PRT. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the relationship between tumor characteristics and secondary enucleation after extra-scleral PRT. Results:Among 465 patients, eecondary enucleation was performed on 78 (16.8%, 78/465) patients during the follow-up period. The 1, 3 and 5 year secondary enucleation rates were 5.4%, 9.3% and 17.1 %, respectively. Eye preservation was successful in 387 cases (83.2%, 387/465). Patients treated by secondary enucleation had a larger maximum basal diameter of tumor, a higher proportion of irregular and diffuse morphology, a cumulative macular involved and a higher AJCC T classification, the difference was statistically significant ( P<0.05). There were 115, 76, 27, and 27 cases of degenerated type, stable type, growth type, and other type, respectively. The tumor thickness of the growth type and other types was significantly smaller than that of the degenerated type and the stable type, and the difference was statistically significant ( P<0.05). Univariate Cox analysis showed that the maximum basal diameter of the tumor ( HR=1.19), tumor thickness ( HR=1.08), AJCC T classification ( HR=1.90), growth type response pattern (relative to degenerated type response pattern) ( HR=4.20) was associated with failure of eye preservation ( P<0.05). In the multivariate Cox analysis, the largest tumor basal diameter ( HR=1.24) and the growth type response pattern (relative to the degenerated type response pattern) ( HR=4.59) were still associated with failure of eye preservation ( P<0.05). Conclusions:The tumor thickness of UM patients with growing and other response patterns after PRT is smaller before treatment; the maximum basal diameter of the tumor and the growing response pattern are independent risk factors for secondary enucleation.

Long-term results of visual function in posterior uveal melanoma patients treated with I125 episcleral brachytherapy in a Spanish referral Ocular Oncology Unit / Resultados de longo prazo da função visual em pacientes com melanoma uveal posterior tratados com braquiterapia epiescleral com I125 em uma unidade de referência em Oncologia Oftalmológica na Espanha

ABSTRACT Purposes: We analyzed patient, tumor and dosimetric characteristics of subjects in a Spanish population diagnosed with uveal melanoma treated with iodine 125 (I125) episcleral brachytherapy, who presented with post-treatment loss of useful visual acuity and global evolution of visual acuity. Methods: A single historic observational cohort study was undertaken. Patients with uveal melanoma were recruited between September 1995 and June 2015. Clinical, tumor and dosimetric data collection and visual acuity evaluations were performed under everyday practice conditions based on a useful visual acuity >0.1 on the decimal scale. The baseline analysis was performed using descriptive and survival analyses according to Kaplan-Meier curves. Results: A total of 286 of the 665 patients diagnosed with uveal melanoma received episcleral brachytherapy, and 198 were included in the study. The mean follow-up time was 75.3 months (95% CI = 68.0-82.6). Patients with post-treatment useful visual acuity loss (n=94, 47%) presented the following characteristics: visual symptoms (n=80, p-value = 0.001); iris color (brown n=33, hazel green n=49, p-value = 0.047); Collaborative Ocular Melanoma Study size (medium n=80, p-value = 0.159); tumor, node, metastasis stage (T2: n=38, T3: n=38, p=0.012); shape (nodular n=67, mushroom-shaped n=26, p=0.001); posterior pole involvement (n=47, p=0.04); recurrence (n=10, p=0.001); and dose administered in the fovea, optic nerve and center of the eye (p<0.002). Using Kaplan-Meier analysis, the mean overall survival of useful visual acuity was 90.19 months, and the probability of preserving useful visual acuity was 66% for one year, 45% for five years and 33% for ten years. Conclusion: Patients most likely to present with visual acuity loss were those with the following profile: elderly males with dark irises who were diagnosed with visual symptoms and exhibited a medium/large melanoma with a mushroom shape in the posterior pole (near the fovea and/or optic nerve). All patients treated with episcleral brachytherapy are likely to present with visual acuity loss, which is more pronounced in the first few years following treatment.

RESUMO Objetivo: Analisar características individuais, tu morais e dosimétricas de pacientes diagnosticados com melanoma uveal, tratados através de braquiterapia epiescleral com iodo-125 (I125), que apresentaram perda da acuidade visual útil após o tratamento e analisar a evolução global da acuidade visual em uma população da Espanha. Métodos: Este é um estudo observacional de coorte histórica considerando pacientes com melanoma uveal diagnosticados entre setembro de 1995 e junho de 2015. Foram coletados dados clínicos, tumorais e dosimétricos e medida a acuidade visual em condições de prática clínica diária, considerando uma acuidade visual útil superior a 0,1 na escala decimal. A análise de base foi efetuada por curvas Kaplan-Meier descritivas de sobrevivência Resultados: Um total de 286 dos 665 pacientes diagnosticados com melanoma uveal recebeu braquiterapia epiescleral e 198 deles foram incluídos no estudo. O tempo médio de acompanhamento foi de 75,3 meses (IC 95%: 68,0-82,6). Os pacientes com perda da acuidade visual útil após o tratamento (n=94, 47%) apresentaram as seguintes características: sintomas visuais (n=80, p=0,001), cor da íris (castanha: n=33, castanho-esverdeada: n=49; p=0,047), tamanho de acordo com o Collaborative Ocular Melanoma Study (tamanho médio: n=80, p=0,159), tumor, nódulo, estágio de metástase (T2: n=38, T3: n=38, p=0,012), forma (nodular: n=67, em forma de cogumelo: n=26, p=0,001), envolvimento do polo posterior (n=47, p=0,04), recorrência (n=10, p=0,001) e dose administrada na fóvea, no nervo óptico e no centro do olho (p<0,002). Na análise de Kaplan-Meier, o tempo médio de sobrevivência geral da acuidade visual útil foi de 90,19 meses e a probabilidade de preservação da acuidade visual útil foi de 66% por um ano, 45% por 5 anos e 33% por 10 anos. Conclusão: O perfil de paciente com maior probabilidade de perda da acuidade visual útil é o de homem idoso com íris escura, diagnosticado com sintomas visuais e melanoma de tamanho médio a grande, em forma de cogumelo no polo posterior (próximo à fóvea, ao nervo óptico ou a ambos). Todos os pacientes tratados com braquiterapia epiescleral terão perda da acuidade visual, mais pronunciada nos primeiros anos após o tratamento.

Bioinformatic analysis between epithelioid and mixed uveal melanoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the differentially expressed genes and crucial genes between epithelioid and mixed uveal melanoma(UM)based on bioinformatics analysis.<p>METHODS: Microarray datasets GSE22138 was extracted from gene expression omnibus database(GEO). The differentially expressed genes(DEGs)were screened out between epithelioid and mixed UM, and functional enrichment analysis were performed with DAVID database. STRING and cytoscape was applied to explore the protein-protein interaction(PPI)network and hub genes. Subsequently, cBioPortal was applied to explore the network of the hub genes, and GEPIA was adopted to study the survival analysis of hub genes.<p>RESULTS: Overall, 241 DEGs including 125 upregulated and 116 down regulated genes were identified. The DEGs mainly enriched in cell adhesion, response to drug and Positive regulation of endothelial cell proliferation. A total of 10 hub genes were identified. Survival analysis revealed the hub genes was associated with the prognosis of UM.<p>CONCLUSION: DEGs and hub genes identified by Bioinformatics analysis in the present study would be beneficial to understand mechanism and biological characteristics between epithelioid and mixed UM.

Scleral necrosis in patients with posterior uveal melanomas evaluated by transcleral fine needle aspiration biopsy and treated by 125I plaque / Necrose escleral em pacientes com melanoma da úvea posterior avaliados pela biópsia aspirativa com agulha fina e tratados com placa de Iodo 125

ABSTRACT Purpose: To evaluate the incidence, potential correlation with transcleral fine needle aspiration biopsy, and treatment of scleral necrosis in patients with posterior uveal melanomas treated by 125I plaque radiotherapy and assessed by transcleral fine needle aspiration biopsy. Methods: We per­formed a retrospective review of posterior uveal melanoma treated by 125I plaque radiotherapy at a single academic institution between July 2006 and July 2013. Consecutive patients diagnosed with a posterior uveal melanoma during the study period that had an anterior margin at or anterior to the equator who were evaluated by transcleral fine needle aspiration biopsy prior to 125I plaque radiotherapy were included. The main outcome measure was development of scleral necrosis, and the secondary outcome was treatment of this complication. Statistical analysis included computation of conventional descriptive statistics, cross-tabulation and chi-square tests of potential factors related to the development of scleral necrosis, and summarizing of treatment approaches and results. The incidence of treatment of scleral necrosis was calculated using the Kaplan-Meier method. Results: During the 7-year study period, 87 posterior uveal melanomas were evaluated by transcleral fine needle aspiration biopsy and treated by 125I plaque radiotherapy. The median largest basal diameter of the tumor was 13.3 mm, and the median thickness was 6.8 mm. Eight patients (9.2%) developed scleral necrosis during follow-up. Thicker tumors (> 6.5 mm) were more likely to develop scleral necrosis (n=7) than thinner tumors (p=0.05). The median interval between 125I plaque radiotherapy and detection of scleral necrosis was 19.1 months. The overall cumulative probability of scleral necrosis was 6.2% at 6 months and 14.3% at 24 months, subsequently remaining stable. For thicker tumors, the probability of scleral necrosis was 23.5% at 45.4 months. Five patients were treated by scleral patch graft (62.5%) and three by observation (37.5%). One patient underwent enucleation after two failed scleral patch attempts and recurrent scleral necrosis. The mean follow-up period for patients with scleral necrosis was 34.5 months. Conclusions: Thicker posterior uveal melanomas are more likely to develop scleral necrosis after 125I plaque radiotherapy and transcleral fine needle aspiration biopsy. While observation is sufficient for managing limited scleral necrosis, scleral patch graft is a viable alternative for eye preservation in extensive scleral necrosis.

RESUMO Objetivo: Avaliar incidência, possível correlação da biópsia aspirativa com agulha fina trans-escleral e manejo da necrose escleral em pacientes com melanoma da úvea posterior tratados com placa de Iodo-125 (PLACA) avaliados pela biópsia aspirativa com agulha fina trans-escleral. Métodos: Revisão retrospectiva de melanoma da úvea posterior tratados com placa de Iodo-125 entre 07/2006 e 07/2013 em uma única instituição acadêmica. Pacientes diagnosticados consecutivamente com melanoma da úvea posterior durante o intervalo desse estudo cuja margem anterior está no equador ou anterior ao mesmo e foram avaliados pela biópsia aspirativa com agulha fina trans-escleral antes do tratamento com PLACA foram incluídos. O principal desfecho avaliado foi desenvolvimento de necrose escleral e o desfecho secundário foi o manejo dessa complicação. Análise estatística incluiu computação de variáveis descritivas convencionais; tabulação e teste do Chi-quadrado de fatores potencialmente relacionados com o desenvolvimento de necrose escleral e sumarização do manejo dessa complicação. A incidência de necrose escleral foi calculada usando o método de Kaplan-Meier. Resultados: Durante o período de 7 anos desse estudo, 87 melanomas da úvea posterior foram avaliados pela biópsia aspirativa com agulha fina trans-escleral e tratados com placa. A mediana do maior diâmetro basal tumoral foi 13,3 mm e a mediana da espessura foi 6,8 mm. Oito pacientes (9,2%) desenvolveram necrose escleral durante o período de acompanhamento. Tumores mais espessos (> 6,5 mm) foram mais propensos a desenvolver necrose escleral (n=7) que tumores mais finos (p=0,05). O intervalo mediano entre PLACA e a detecção da necrose escleral foi 19,1 meses. Probabilidade cumulativa de desenvolvimento de necrose escleral foi 6,2% em 6 meses e 14,3% em 24 meses permanecendo estável subsequentemente. Em tumores espessos, a probabilidade de necrose escleral foi 23,5% em 45,4 meses. Cinco pacientes foram manejados com enxerto escleral (62,5%), 3 foram observados (37,5%). Um paciente foi enucleado após 2 enxertos esclerais com necrose escleral recidivada. Tempo de seguimento médio dos pacientes com necrose escleral foi 34,5 meses. Conclusões: Tumores espessos pareceram mais propensos a desenvolver necrose escleral após PLACA e biópsia aspirativa com agulha fina trans-escleral para melanoma da úvea posterior. Apesar de observação para necrose escleral limitada ser suficiente, enxerto de esclera é uma alternativa viável para preservação ocular em necrose escleral extensa.

Treatment for radiation retinopathy of uveal melanoma undergone radiotherapy: the current situation / 中华眼底病杂志

Radiotherapy is the prior treatment for uveal melanoma,but a major problem confronted most of the patients is radiation retinopathy,which accompanied with severe visual loss and secondary enucleation potential.There is no optium choice and normative strategy so far,the intraocular melanoma society has focused on application of anti-vascular endothelial growth factor drugs injection and glucocorticoids.This article reviews a series of potential managements for radiation retinopathy and its further stage.

Evaluation of nicotinamide as an anti-inflammatory and anti-angiogenic agent in uveal melanoma cell lines / Avaliação da nicotinamida como agente anti-inflamatório e anti-angiogênico em linhas celulares de melanoma uveal

ABSTRACT Purpose: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. Methods: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. Results: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. Conclusions: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

RESUMO Objetivo: Acredita-se que a nicotinamida (NIC) seja capaz de diminuir a angiogênese induzida pelo fator de crescimento endotelial vascular (VEGF). Investigar os efeitos da nicotinamida sobre a secreção de citocinas pró-angiogênicas e pró-inflamatórias em linhagens de células de melanoma uveal humano (UM). Métodos: Duas linhagens de células humanas de UM (92,1 e OCM-1) foram tratadas com NIC (10 mmol/L) ou apenas com meio de cultura por 48 horas. O sobrenadante das culturas obtido após a administração de nicotinamida foi comparado com o sobrenadante das culturas controle quanto à expressão de 20 fatores pró-angiogênicos e pró-inflamatórios, pela técnica de enzyme-linked immunosorbent assay (ELISA). Resultados: Sete citocinas pró-angiogênicas foram detectadas nas condições de controle em ambas as linhagens de células de UM. O tratamento com nicotinamida promoveu uma redução significativa da secreção das seguintes citocinas angiogênicas: Angiogenina, ANG2, EGF e VEGF-A em células 92.1; bFGF em células OCM-1; PIGF em ambas as linhagens celulares. Quanto às proteínas pró-inflamatórias, a expressão de MCP-1 e IL-8 foi significativamente reduzida com a administração de nicotinamida em relação às culturas de células que não receberam o tratamento. Conclusões: Nicotinamida apresenta propriedades anti-inflamatórias e anti-angiogênicas em modelo experimental in vitro. Tais efeitos sugerem a possibilidade de utilizar esta substância na quimioprevenção do UM. Entretanto, estudos com modelos experimentais in vivo são necessários para melhor avaliar o benefício do tratamento do UM com nicotinamida.

Apresentação incomum e agressiva de melanoma intraorbitário / Unusual and aggressive presentation of intraorbital melanoma

RESUMO O objetivo dos autores é relatar um caso de melanoma intraorbitário de apresentação atípica e agressiva, formando grande massa dolorosa de aspecto eritematoso e inflamatório projetando-se da órbita esquerda com o globo ocular danificado em seu ápice. A análise da peça identificou melanoma maligno com componentes celulares epitelióide, fusocelular e anaplásico.

ABSTRACT The purpose of this study is to report a intraorbital melanoma case with atypical and aggressive presentation, forming a large painful mass with erythematosus and inflammatory aspect protruding from the left orbit with eyeball damaged at its peak. Piece analysis identified malignant melanoma compound of epithelioid, spindle and anaplastic cells.

Internal eye wall resection of uveal tumors: long-term evaluation / Ressecção em bloco de tumores uveais: avaliação de longo prazo

The authors report five cases of uveal tumors managed with internal eye wall resection and evaluate the long-term results. Patient age varied from 31 to 61 years. Four patients were female and one was male. Uveal tumors involved ciliary body and choroid in three patients and choroid alone in the other two. Histopathological examination demonstrated three uveal melanomas, one leiomyoma, and one meduloepithelioma. The largest tumor diameter ranged from 8 to 15 mm and tumor thickness from 5 to 11 mm. Follow-up of the patients was over a period of 6 to 23 years. Final visual acuity was 20/20 in 3 patients and 20/200 in one patient, and in the fifth patient, the affected eye was enucleated. No cases of metastatic disease or local recurrence of the tumor were observed, suggesting that internal eye wall resection is a valid alternative for the treatment of selected cases of uveal tumors.

Os autores relatam 5 casos que apresentavam tumores uveais e foram submetidos à remoção cirúrgica em bloco do tumor, avaliando resultados de acuidade visual, índice de retenção do globo ocular e de doença metastática. Quatro mulheres e um homem, com idade entre 31 e 61anos foram submetidos ao procedimento. O tumor envolvia corpo ciliar e coroide em três olhos e somente a coroide em dois. A histopatologia demonstrou que 3 tumores eram melanomas, um leiomioma e um meduloepitelioma. O maior diâmetro dos tumores foi entre 8 e 15 mm e a espessura entre 5 e 11 mm. O tempo de seguimento dos pacientes foi de 6 a 23 anos. A acuidade visual final foi de 20/20 em 3 olhos, 20/200 em outro e um olho foi enucleado. Não foram observados casos de doença metastática ou recorrência tumoral, sugerindo que a ressecção em bloco de tumores uveais é uma alternativa válida para o tratamento destes tumores em casos selecionados.

Analysis of differentially expressed genes and metabolic pathways in human uveal melanoma / 中华实验眼科杂志

Background Studies showed that there exsits differential gene expression in human uveal melanoma (UM).However, the researching results are somewhat inconsistently abroad, while relevant literature is still less in China.Few domestic researches have reported the abnormalities of gene transcription level or the pathways of these genes.Objective This study was to compare the gene expression profiles between human UM and normal uvea tissues and analyze the metabolic pathways involved in these differentially expressed genes.Methods Four human UM samples were collected in Beijing Tongren Eye Center,and 4 pieces of normal uveal tissues from 4 donors served as controls.The expression of genes was detected with Human Genome U133 Plus 2.0 chip,and the expression profiles were compared between two groups.The biological functions and active pathways of the genes were analyzed by Gene Ontology Enrichment Analysis Software Toolkit (GOEAST).Results Compared with the normal controls,4 165 differential genes were screened in human UM (12.50％) ,including 1 236 up-regulated genes (3.71％) and 2 929 down-regulated genes (8.79％) ,in which the genes of raised more than 5-, 10-,50-and 100-fold were 113,21,1 and 1, respectively, and the genes of reduced by 50％ ,90％ ,98％ and 99％ were 1 053,422,33 and 5,respectively.The functions of these differentially expressed genes were associated with cellular differentiation and growth,development, cell adhension, immun response, transcriptional contol, signal transduction and anti-apoptosis.The metabolic pathways of differentially expressed genes included angiogenesis pathway, cell-cycle related protein kinase pathway and immune regulatory pathway (involving B lymphocytes and T lymphocytes).ConclusionsGene expression profiles are evidently different between human UM and normal uveal tissue.The variation of the gene profiles in human UM leads to the changes of multiple biological functions including angiogenesis and kinase pathway even immun system.It is implied that the pathogenesis of human UM is a comprehensive effect of multiple genes and biological pathways.

Understanding intraocular neoplasms from the perspective of ocular pathology / 中华实验眼科杂志

Ocular pathology is an important branch of histopathology,which plays a key role in understanding and revealing ocular diseases.In ophthalmology, retinoblastoma (RB) and uveal melanoma (UM) are common primary malignant intraocular neoplasms,which seriously endanger patients' lives.About two thirds of RB patients are caused by sporadic somatic mutations in the Rb1 gene,and the other one third of RB patients are caused by germline mutations in the Rb1 gene,which occur in the early age,are usually bilateral and transmissible to offsprings.High-risk histopathologic factors of RB mainly include the retrolaminar optic nerve invasion and/or massive choroidal invasion,and these are main indications for postoperative adjuvant chemotherapy.At present, due to lack of effective systemic therapy, about half of UM patients succumb to distant metastasis, most of which are hepatic metastases.Poor prognostic indicators of intraocular neoplasms include large tumor, ciliary body involvement, epithelioid cell type, extraocular diffusion,etc.Monosomy 3 and class 2 gene expression profile are currently accurate and objective prognostic indicators.

Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy / Implicação prognóstica da classificação citopatológica dos tumores melanocíticos da úvea avaliados pela biópsia aspirativa com agulha fina

PURPOSE: Determine whether cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy (FNAB) is a significant prognostic factor for death from metastasis. METHODS: Retrospective analysis of cases of clinically diagnosed uveal melanoma evaluated by fine-needle aspiration biopsy from 1980 to 2006. Main outcome evaluated was death from metastasis. Associations between baseline clinical variables and cytopathologic classification were evaluated using cross-tabulation. Prognostic significance of cytopathologic classification was evaluated by Kaplan-Meier and Cox proportional hazards analysis. RESULTS: Of 302 studied biopsies, 260 (86.1%) yielded sufficient cells for cytopathologic classification. Eighty of the 260 patients who had a sufficient specimen have already died (P=0.021), 69 from metastatic uveal melanoma. Cell type assigned by cytopathology was strongly associated with metastasis/metastatic death in this series (P=0.0048). Multivariate analysis showed cytopathologic classification to be an independently significant prognostic factor for metastatic death (P=0.0006). None of the 42 patients whose tumor yielded insufficient aspirates (sampled in at least two sites) have developed metastasis or died of metastasis thus far. CONCLUSION: In this series, cytopathology of fine-needle aspiration biopsy samples obtained from uveal melanomas was strongly prognostic of death from metastasis. Insufficiently aspirates (2 or more sites sampled) proved to be prognostic of a favorable outcome (i.e., not developing metastasis).

OBJETIVO: Determinar se a classificação citopatológica de tumores melanocíticos da úvea avaliados pela biópsia aspirativa com agulha fina (BAAF) é um fator prognóstico significativo para óbito por metástases. Métodos: Análise retrospectiva de casos diagnosticados clinicamente como melanoma uveal e avaliados pela biópsia aspirativa com agulha fina entre 1980 e 2006. O evento principal analisado foi óbito por metástase. Associações entre variáveis clínicas à apresentação e classificação citopatológica foram avaliadas usando tabulação cruzada. Significância prognóstica da classificação citopatológica foi avaliada por análise de riscos proporcionais de Cox e Kaplan-Meier. RESULTADOS: Das 302 biópsias estudadas, 260 (86,1%) renderam um número suficiente de células para classificação citopatológica. Oitenta dos 260 pacientes que obtiveram um espécime suficiente (adequado) foram a óbito (P=0,021), 69 destes por melanoma uveal metastático. O tipo celular designado pela citopatologia apresentou forte associação com metástase/óbito por metástase nessa série (P=0,0048). Análise multivariada mostrou que a classificação citopatológica foi um fator prognóstico independente significativo para o óbito por metástase (P=0,0006). Nenhum dos 42 pacientes cujos tumores renderam um aspirado insuficiente (quando foram amostrados pelo menos 2 sítios) desenvolveu metástase e foi a óbito por metástase até o presente momento. CONCLUSÃO: Nessa série, a citopatologia dos espécimes obtidos pela biópsia aspirativa com agulha fina de melanomas uveais foi fortemente prognóstica para óbito por metástase. Os aspirados insuficientes (se duas ou mais áreas foram amostradas) provou ser um resultado prognóstico favorável (i.e., de não desenvolvimento de metástases).

Clinical manifestation and ophthalmoscopic image characteristics of uveal metastatic carcinoma / 中华眼底病杂志

Objective To observe the clinical manifestation and ophthalmoscopic image characteristics of uveal metastatic carcinoma.Methods Thirty-six uveal metastatic carcinoma patients (43 eyes) were enrolled in this study.The patients included 21 males and 15 females.The patients' ages ranged from 28 to 71 years,with a mean age of (47.3 ±10.2) years.Seven patients had bilateral carcinoma and 29 patients had unilateral carcinoma.There were 30 patients with lung cancer,three patients with breast cancer,one patient with gastric cancer and two patients without primary tumors.There were 20 patients with known primary cancer,16 patients visited the Department of Ophthalmology first.All the patients were examined documenting visual acuity,intraocular pressure,slit-lamp microscopy and mydriatic fundus examination.Meanwhile,22 patients (26 eyes) were examined using B-type ultrasound and/or color Doppler flow imaging(CDFI).Twelve patients (12 eyes) were examined using fundus fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA).Seventeen patients (22 eyes) were examined using MRI and/or CT.The clinical manifestation and ophthalmoscopic image characteristics of uveal metastatic carcinoma patients were observed.Results Among 43 eyes,four lesions were in the iris,three lesions in the ciliary body and 32 lesions were in the choroid.Fundus examination showed an isolated mass in 26 eyes and more than two masses in nine eyes.Metastatic tumors of the iris and ciliary body often showed irregular cauliflower-like mass with gray-white or meat-red color and abundant vessels.The choroidal metastasis usually demonstrated flat rounded or irregular intraocular masses with gray-yellow or gray-white color in the posterior pole.B-type ultrasound showed ill-defined,flat,and irregular-shaped masses with uneven internal reflectivity.CDFI showed rich blood flow within the tumor.FFA and (or)ICGA showed pinpoint and mottled leaks against hyperfluorescence background.MRI revealed low or middle signal using T1 WI and low signal intensity using T2WI.Conclusions The uveal metastatic carcinoma usually occurs in one eye with an isolated mass.Most of them show a flat gray-yellow mass in posterior choroids and have the primary cancer sites of the lung.FFA and/or ICGA show pinpoint and mottled leaks against hyperfluorescence background.B-type ultrasound and (or) CDFI show ill-defined,flat,and irregular-shaped mass with rich blood flow within the tumor.MRI reveals low signal intensity on T2 WI.

Melanoma de corpo ciliar e coróide: relato de caso / Choroidal and ciliary body melanoma: case report

Melanomas oculares correspondem a 5 por cento de todos os melanomas e 85 por cento deles têm origem no trato uveal. Melanoma uveal é o tumor maligno intraocular primário mais comum no adulto. Relatamos neste artigo um caso de melanoma uveal em paciente, sexo feminino, 31 anos, com quadro de fotopsia, hiperemia e baixa da acuidade visual no olho esquerdo com evolução de quatro meses. Apresentava ao exame oftalmológico acuidade visual menor que 20/400, grande massa tumoral na região nasal retroiriana, com deslocamento anterior do cristalino, estreitamento da câmara anterior e descolamento seroso da retina. A ecografia sugeriu tratar-se de grande massa tumoral suspeita de melanoma de coróide com invasão do corpo ciliar. A confirmação diagnóstica foi possível por meio do exame anatomopatológico.

Ocular melanomas correspond to 5 percent of all melanomas and 85 percent of them have its origin in the uveal tract. Uveal melanoma is the most commom primary intraocular malignant tumor in the adult. In this article, a case of uveal melanoma in a 31 year-old female patient, with photopsia, hyperemia and low visual acuity in the left eye with evolution of 4 months is presented. In the ophthalmologic examination, visual acuity was lower than 20/400, a large tumoral mass was noted at the nasal region behind the iris with anterior lens displacement, anterior chamber narrowing and serous retinal detachment. The ocular echography suggested a large tumoral mass as a choroidal melanoma extending to the ciliary body. The confirmation diagnosis was possible through the histopathologic examination.

A Case of Ciliary Body Melanocytoma Presenting as a Painful Iris Mass

We report a case of ciliary body melanocytoma in a Korean patient, which presented as an intermittently painful pigmented iris mass and was successfully managed by iridocyclectomy. A 52-year-old healthy man presented with an irregularly-shaped and heavily-pigmented mass at the iris root of his right eye. Visual acuity of the right eye was 20/20 with normal intraocular pressure. Ultrasound biomicroscopy showed a 1.5x1.3-mm ciliary-body mass with extension into the iris root. Iridocyclectomy with scleral resection under a lamellar scleral flap was performed, and the histopathologic features of the resected tissue were consistent with melanocytoma of the ciliary body. The patient's visual acuity remained 20/20 with good postoperative cosmesis. During one year of follow-up, no signs of tumor recurrence were seen, and the patient reported resolution of the intermittent ocular pain in the involved eye.

Evidências obtidas de um caso de melanoma de íris recidivado / Evidences from a case of recurrent iris melanoma

O artigo apresenta uma análise histológica de um caso de melanoma recidivado de íris após sete meses da iridociclectomia, em uma paciente de 45 anos. Após enucleação, o exame histopatológico do globo ocular demonstrou a persistência de um pequeno fragmento do tumor no coto da íris remanescente, evoluindo para recorrência da neoplasia. O caso traz dados para uma discussão sobre a cirurgia conservadora de melanomas oculares, visando uma postura analítica dentro do espírito da Medicina Baseada em Evidência. Um caso raro, com documentação apenas do ponto de vista histopatológico, que motiva a utilização destes achados na discussão do assunto. A não contiguidade do que restou do tumor com as tumorações da recidiva fala em favor da disseminação e proliferação de células neoplásicas nas cirurgias conservadoras.

The article presents a histologic study of a rare recurrent iris melanoma seven months after iridocyclectomy, in a 45-year-old female patient. After enucleation, the histopathological examination of the ocular globe demonstrated the persistence of a small tumor fragment in iridectomy stump, developing the neoplasia recurrence. The case brings data for a discussion about the conservative surgery of ocular melanomas and an analytical position of Evidence Based Medicine. A rare case, with documentation only histopathologic, motivates the use of this finding into the subject matter. The distance of what remained from the tumor with the recurrent tumors reinforces the dissemination and proliferation of neoplastic cells in the conservative surgeries.

Aspectos psicológicos e qualidade de vida em pacientes com melanoma uveal durante o processo de tratamento por remoção do bulbo ocular / Psychological aspects and quality of life in uveal melanoma patients during the treatment process by ocular bulb remotion

OBJETIVO: Avaliar prospectivamente as repercussões emocionais no indivíduo com melanoma uveal e indicação cirúrgica em três momentos: diagnóstico e pré-cirúrgico, pós-cirúrgico e pós-cirúrgico tardio. MÉTODOS: Trata-se de estudo clínico-qualitativo, no qual se utilizaram os seguintes instrumentos: Inventário de Ansiedade Traço/Estado - IDATE; Inventário de Depressão Beck e o Questionário de Qualidade de Vida SF-36. RESULTADOS: Participaram do estudo, inicialmente, 20 pacientes, 13 homens e sete mulheres, com idade média de 52 anos e, num segundo momento, 16 estavam disponíveis. No momento pré-cirúrgico, o Estado de Ansiedade está aumentado em relação ao Traço. O índice de Depressão indica um estado mínimo a leve e a Qualidade de Vida revela que os aspectos físicos e emocionais são os mais afetados. No pós-cirúrgico de três meses, o Traço de Ansiedade está consideravelmente elevado, o índice de Depressão mostra um estado leve a grave e na Qualidade de Vida os aspectos mais atingidos são os físicos, sociais e emocionais, além da vitalidade e da saúde mental. No pós-cirúrgico de um ano, o Traço de Ansiedade se mantém semelhante ao da primeira avaliação, o Estado de Ansiedade diminui consideravelmente, a Depressão cai para um índice mínimo e a Qualidade de vida mostra a maioria dos aspectos equilibrados. CONCLUSÕES: Após três meses da cirurgia, os pacientes se mostram mais frágeis, com dificuldade de adaptação, com aumento do grau de depressão e ansiedade. Esse foi o pior período para os pacientes. Após um ano da cirurgia, mostram-se mais estruturados e com os aspectos de Qualidade de Vida mais equilibrados.

PURPOSE: To evaluate prospectively the emotional repercussions in the individual with uveal melanoma and surgical indication in three phases: diagnosis and preoperative, postsurgery and late postsurgery. METHODS: Clinical qualitative study based on the following instruments: STAI - State, Trait Anxiety Inventory; BDI - Beck Depression Inventory; Quality of Life Questionaire SF-36. RESULTS: The sample of this study consisted of 20 patients, 13 males and seven females, with average age of 52 years. Before surgery: the patients appear fragile and impacted by diagnosis and treatment. The state of depression indicates a minimum to light state. Anxiety has the state increased in relationship to Trait. Quality of Life has the emotional and physical aspects affected. Three months after surgery: the Depression shows to light to serious state. Anxiety has the state considerably increased. Quality of Life has most aspects affected: the physical, vitality, social, mental health and emotional aspects being the most affected. One year after surgery: the State of Anxiety decreases considerable. The Trait of Anxiety is maintained in most patients when compared to the first evaluation. Depression shows a minimum state. Quality of Life has most of its aspects balanced. CONCLUSION: After three months of surgery the patients appear more fragile with adaptation difficulty, Anxiety and Depression increasing. This period revealed to be the worst moment. One year after surgery, they appear more structured and with a more balanced Quality of Life.