Autophagy and vesicular trafficking in human uveal melanoma: A histopathological study.

Uveal melanoma is an ocular tumor with a high risk of developing metastases. The endo-lysosomal system can affect the melanoma progression by accelerating and facilitating invasion or metastasis. This study aims to conduct comparative analysis of normal choroidal melanocytes and uveal melanoma cells ultrastructure with a focus on intracellular transport system, and to examine the patterns of autophagy- and vesicular trafficking-related proteins expression in a case series of uveal melanomas. Transmission electron microscopy was used to assess the ultrastructure of normal choroidal melanocytes and uveal melanoma cells. The expression levels of autophagy- and vesicular trafficking-related proteins in three histological types of uveal melanoma were analyzed by immunofluorescence staining. Electron microscopy results showed that the autophagic vacuoles were more abundant in normal choroidal melanocytes, than in uveal melanoma cells. The normal choroidal melanocytes were characterized by active intracellular vesicular trafficking; however, the proportion of caveolae was higher in uveal melanoma cells. The spindle type of tumor was characterized by a high expression levels of LC3 beta, while Rab7 and Rab11 proteins expression was significantly up-regulated in the mixed-type tumor cells. The results indicate that uveal melanoma cells probably have lower basal levels of autophagy and higher receptor-mediated endocytic trafficking-associated with caveolae than normal choroidal melanocytes. RESEARCH HIGHLIGHTS: The autophagic vacuoles are abundant in normal choroidal melanocytes. Uveal melanoma cells are characterized by a high proportion of caveolae. The high expression levels of LC3 beta were revealed in a spindle type of tumor, while Rab7 and Rab11 proteins expression was up-regulated in the mixed-type tumor cells.

Quantitative Diffusion-Weighted MR Imaging: Is There a Prognostic Role in Noninvasively Predicting the Histopathologic Type of Uveal Melanomas?

Histopathologically, uveal melanomas (UMs) can be classified as spindle cell, mixed cell and epithelioid cell type, with the latter having a more severe prognosis. The aim of our study was to assess the correlation between the apparent diffusion coefficient (ADC) and the histologic type of UMs in order to verify the role of diffusion-weighted magnetic resonance imaging (DWI) as a noninvasive prognostic marker. A total of 26 patients with UMs who had undergone MRI and subsequent primary enucleation were retrospectively selected. The ADC of the tumor was compared with the histologic type. The data were compared using both one-way analysis of variance (ANOVA) (assessing the three histologic types separately) and the independent t-test (dichotomizing histologic subtypes as epithelioid versus non-epithelioid). Histologic type was present as follows: the epithelioid cell was n = 4, and the spindle cell was n = 11, the mixed cell type was n = 11. The mean ADC was 1.06 ± 0.24 × 10-3 mm2/s in the epithelioid cells, 0.98 ± 0.19 × 10-3 mm2/s in the spindle cells and 0.96 ± 0.26 × 10-3 mm2/s in the mixed cell type. No significant difference in the mean ADC value of the histopathologic subtypes was found, either when assessing the three histologic types separately (p = 0.76) or after dichotomizing the histologic subtypes as epithelioid and non-epithelioid (p = 0.82). DWI-ADC is not accurate enough to distinguish histologic types of UMs.

Uveal and conjunctival melanomas: disease course and outcomes in Chinese patients.

INTRODUCTION: Epidemiological studies of ocular melanomas have largely focused on Caucasian populations. This study reviewed the course and outcomes of uveal melanoma (UM) and conjunctival melanoma (CM) in Chinese patients. METHODS: This retrospective study included patients with UM and CM who received treatment in a tertiary eye centre in Hong Kong from January 1994 to December 2019. Data were recorded concerning patient demographics, tumour laterality, tumour characteristics, investigations performed, treatment regimen, and final outcomes. RESULTS: During the 25-year study period, there were 13 patients with UM and 11 patients with CM who did not display nodal or systemic involvement at diagnosis. The mean ± standard deviation ages at diagnosis of UM and CM were 59 ± 15.8 and 57 ± 13.9 years, respectively. There were more men among patients with UM than among those with CM (P=0.042). Most patients with UM underwent primary enucleation (n=12; 92.3%), whereas most patients with CM underwent orbital exenteration (n=9; 81.8%). The prognosis was significantly worse for CM than for UM. The median disease-free survival were 5.2 years (range, 0.7-20.5) and 2.1 years (range, 0.1-24.9) for UM and CM, respectively. Melanoma-related mortality was significantly higher among patients with CM than among those with UM (P=0.006). CONCLUSION: Compared with UM, CM has higher rates of systemic metastasis and tumour-related mortality in Hong Kong Chinese patients, regardless of prior definitive treatment.

Psychometric Results of a New Patient-Reported Outcome Measure for Uveal Melanoma Post-Brachytherapy Treatment: The PROM-UM.

The objective of this study was to evaluate the psychometric properties of a new patient-reported outcome instrument intended for use with patients who have undergone brachytherapy for uveal melanoma (PROM-UM). Classical test theory and item response theory were used to evaluate the performance of individual items and domains. A convenience sample of 439 participants who had undergone brachytherapy for uveal melanoma from one of three North American ocular oncology treatment centers were included in this cross-sectional study. Exploratory factor analysis identified three domains which were labelled "Symptom Impairment", "Worry", and "Discomfort". The acceptability of the instrument was supported by little missing data (range = 0.00-1.14%) and low maximum endorsement (range = 0.00-1.82%). Item-total (range = 0.68-0.85) and inter-item (range = 0.74-0.80) correlations indicated acceptable reliability. Discrimination and difficulty were assessed using item response theory. Items in all three domains indicated moderate to very high discrimination (range = 1.00-4.10). Two items in the Symptom Impairment domain were too difficult to measure. Response ranges in the other two domains demonstrated acceptable difficulty. These results from the study indicate that this new patient-reported outcome instrument can be used with patients treated with brachytherapy for uveal melanoma. Providers could use this instrument to help inform post-treatment management.

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

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.

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.

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.

Management of primary choroidal lymphoma presenting as extensive serous retinal detachment and salmon patch of bulbar conjunctiva: a case report.

BACKGROUND: We describe the outcome of ultra-low-dose radiotherapy plus intravitreal methotrexate and rituximab injections for a patient with primary choroidal lymphoma who presented with nodular conjunctival salmon patches and extensive serous retinal detachment. CASE PRESENTATION: A 34-year-old Iranian man presented with a nodular patch of bulbar conjunctiva in the right eye, and 1+ vitritis. A nearly complete shallow serous retinal detachment, retinal folds, and multifocal yellow choroidal infiltrates were seen during a fundus examination of the right eye. Enhanced depth imaging optical coherence tomography revealed macular retinal folds and an uneven, undulating, "seasick" appearance of the choroidal surface with choriocapillaris compression, intraretinal and subretinal fluid, and clusters of optically dense material at the outer retinal level. An incisional biopsy of the conjunctival lesion confirmed the diagnosis of primary choroidal lymphoma with epibulbar involvement. The patient was treated with ultra-low-dose "boom-boom" radiation (4 Gy delivered in two fractions over two consecutive days) as well as intravitreal methotrexate and rituximab injections. After a year, the lesions had completely disappeared, with no adverse effects or recurrence. CONCLUSION: Ultra-low-dose (boom-boom) radiotherapy combined with intravitreal chemotherapy and/or immunotherapy may be an effective treatment for primary choroidal lymphoma with anterior epibulbar extension and diffuse subretinal fluid with favorable response and minimal side effects.

Retrospective analysis of secondary enucleation for uveal melanoma after plaque radiotherapy.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Plaque brachytherapy (PRT) is widely accepted as an effective globe-conserving treatment modality for UM. However, local treatment failure and complications lead to the enucleation of irradiated eyes. We conducted this study to explore the causes and long-term prognosis for UM patients who accepted secondary enucleation after plaque radiotherapy. METHODS: This was a retrospective cohort study. Data of patients who underwent secondary enucleation for UM after plaque radiotherapy, from July 2007 to July 2019, at Beijing Tongren Hospital were analyzed. Kaplan-Meier analysis was performed to assess the probability of indications, metastasis, and metastasis-related death. Cox regression analysis was used to analyze associations of the prognostic factors. RESULTS: Eight hundred and eighty patients were clinically diagnosed with uveal melanoma and initially treated by iodine-125 plaque radiotherapy, 132 of whom underwent secondary enucleation and pathological examination in the same hospital. Fifty-two (39.4%) eyes were enucleated simply because of uncontrollable neovascular glaucoma (NVG). Forty-four (33.3%) patients suffered from tumor recurrence. Tumor non-response occurred in 18 (13.6%) cases. Ten (7.6%) eyes received enucleation entirely due to other types of glaucoma. Failure to preserve the eyes for other reasons occurred in eight (6.1%) patients. At a median follow-up of 58.1 [IQR: 40.9-90.5] months, the systemic spread was detected in 45 (34.1%) patients, and 38 of them died. On multivariate analysis, tumor largest basal diameter (HR 1.15 [95% CI: 1.01, 1.31]), tumor non-response (HR 7.22 [95% CI: 2.63, 19.82]), and recurrence (HR 3.29 [95% CI: 1.54, 7.07]) were risk factors for metastasis. Increased age (HR 1.54 [95% CI: 1.07, 2.23]), tumor non-response (HR 7.91 [95% CI: 2.79, 22.48]), and recurrence (HR 3.08 [95% CI: 1.13, 7.23]) were risk factors for metastasis-related death. CONCLUSIONS: NVG was the major reason for secondary enucleation for Chinese UM patients after PRT. Tumor non-response and recurrence were associated with a significantly higher risk of long-term metastasis and metastasis-related death.

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results.

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

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.

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.

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.

[The clinical observation of external scleral plaque radiotherapy in patients with uveal melanoma].

Objective: To investigate the safety and efficacy of external scleral plaque radiotherapy (PRT) in the treatment of uveal melanoma (UM). Methods: This was a retrospective case series study. The data of 819 patients who underwent ophthalmic PRT from July 2007 to November 2017 at Tongren Hospital Affiliated to Beijing Capital Medical University was collected, including preoperative visual acuity, intraocular pressure and slit lamp microscope, color fundus photography, indirect ophthalmoscopy, color Doppler ultrasound, fundus fluorescein angiography, indocyanine green angiography, orbital nuclear magnetic resonance imaging, PRT times and time, complications, follow-up time, the maximum basal diameter and height of the tumor UM half a year after the applicator was removed, tumor metastasis rate, mortality and visual acuity observed at the last follow-up. The tumor growth was considered when the tumor height increased by 2.0 mm or the extension of any boundary of the tumor was 2.5 mm; otherwise, the treatment was defined as effective. The paired t test and Kaplan-Meier survival curve were used for statistical analysis. Results: There were 408 males and 411 females. The age ranged from 13 to 85 years (mean, 47 years). Nine patients had ciliary body melanoma, 43 patients had choroidal melanoma involving the ciliary body, and 767 patients had choroidal melanoma. In all 819 eyes, the tumor was medium-sized in 697 eyes and large in 110 eyes. All patients were treated with PRT only one time. The average radiotherapy time was 15 days (range, 6 to 50 d). All operations were successfully completed, with no active bleeding, infection, adjacent tissue injury and other related complications. At 6 months after the treatment, the maximum basal diameter of the tumor was (12.41±3.20) mm, which was significantly different from that before treatment (12.82±3.21) mm (t=2.40, P<0.01); the tumor height was (6.18±2.55) mm, which was significantly different from that before treatment (7.21±2.57) mm (t=4.05, P<0.01). The average follow-up time was (34±24) months (range, 1 to 125 months). Twenty-five patients lost follow-up at 2 years after the PRT, and 71 patients underwent enucleation. The effective rate of the PRT treatment was 88.3% (723/819), and the eyeball retention rate was 91.1% (723/794). The visual acuity remained stable in 393 eyes, decreased in 344 eyes, and improved in 82 eyes. Sixty patients had systemic metastasis (liver, bone or breast metastasis). Twenty-two patients died of tumor metastasis. The 5-year metastasis rate was 12.8%; the 5-year mortality rate was 5.8%; the 10-year metastasis rate was 20.6%; the 10-year mortality rate was 5.8%. Conclusions: PRT is safe and effective in the treatment for UM and can preserve some useful visual acuity. PRT can be used as the main treatment for medium-sized UM.(Chin J Ophthalmol, 2020, 56: 670-675).

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.

[Complications and status quo of plaque radiotherapy for uveal melanoma].

Radiation treatment, including episcleral plaque radiotherapy, stereotactic radiosurgery, proton beam therapy and so on, is the primary eye-conserving choice for uveal melanoma. But the complications resulted from radiotherapy's nonselective kill to tumor cells can be visual-threatening and eventually result in the enucleation of eyeball. This review summarizes current radiation strategies for uveal melanoma and how these complications occur, develop and present, in the hope that it could provide insights for the radiation interventions and diagnosis of radiative complications. (Chin J Ophthalmol, 2018, 54: 707-711).