No abstract

Background The immune response has been implicated in the control of uveal melanoma progression. Epigenetic mechanisms mediated by specific microRNAs (miRs) regulate immune responses. Methods Blood was drawn from six patients with uveal melanoma followed from diagnosis, at which time there was no clinical or radiographic evidence of metastasis, until metastasis manifested. Circulating T cell, natural killer (NK), natural killer T (NKT), and myeloid suppressor cell populations were assessed by flow cytometry. CD3+, CD15+, and CD56+ cells were isolated using immunomagnetic beads. Plasma and cellular levels of immune regulatory miRs were determined by quantitative polymerase chain reaction assays. Results The development of metastasis was associated with decreases in circulating CD3−CD56dim NK cells and CD8+ and double-negative CD3+CD56+ NKT cells. ICOS+CD4+FoxP3+ T regulatory cells and CD11b+CD14−CD15+ myeloid suppressor cells increased. Plasma levels of miR-20a, 125b, 146a, 155, 181a, and 223 were higher in the study patients at diagnosis compared to controls. Plasma levels of miR-20a, 125b, 146a, 155, and 223 increased, and miR-181a decreased when metastasis manifested. Alterations in immune regulatory miRs were also observed in CD3+, CD15+, and CD56+ cell populations. Conclusions The development of metastasis in uveal melanoma is associated with changes in immune effector and regulatory cells consistent with lessening tumor immune surveillance. These changes are associated with changes in plasma and cellular levels of immune regulatory miRs. The results may help guide uveal melanoma immunotherapy and biomarker development.

No abstract

No abstract

Traditionally the paraneoplastic retinopathies have been classified into two groups: melanoma-associated retinopathy (MAR) and cancer-associated retinopathy (CAR). MAR occurs in individuals with metastatic cutaneous or uveal melanoma and is characterized by nyctalopia, photopsias, and variable vision loss. In most cases, the fundus is essentially normal in appearance. More recently, there have been multiple reports of a MAR-like retinopathy with associated detachments of the retinal pigment epithelium (RPE) and neurosensory retina. Such a clinical presentation has been termed paraneoplastic vitelliform retinopathy. In the present report, we describe an 80-year-old male with metastatic cutaneous melanoma who developed paraneoplastic vitelliform retinopathy. For the first time, histopathology from enucleation specimens provides a clinicopathologic disease correlation with focal abnormalities in the inner nuclear and outer plexiform layers.

Acta Ophthalmol. 2010: 88: e334–e340 Abstract. Purpose:  Single‐centre consecutive interventional case series by retrospective chart review to evaluate the efficacy of verteporfin (Visudyne™) photodynamic therapy (PDT) of retinal capillary haemangioma (RCH). Methods:  Following an initial period of observation, six eyes of five patients with RCH (juxtapapillary 3 and extrapapillary (EP) 3) received 1–3 sessions of standard verteporfin PDT upon the development of progressive vision‐threatening complications. Four of the five patients had von Hippel‐Lindau (VHL) disease. Follow‐up included documentation of best‐corrected Snellen visual acuity (BCVA), tumour regression, and presence or absence of subretinal fluid (SRF) and/or lipid exudation as assessed by dilated fundus examination (DFE), fundus photos, and optical coherence tomography (OCT). These parameters were documented at 1 week, 1 month, and 3 months following each PDT session and up to 32 months following the first PDT. Results:  All eyes showed favourable response to PDT as defined by tumour regression or stabilization as well as improvement of SRF and lipid exudation. BCVA improved or stabilized in three eyes. Three eyes required PDT retreatment for recurrent SRF. Epiretinal membrane (ERM) worsened in three eyes, requiring vitreoretinal surgery at a median of 6 months following PDT. Conclusions:  PDT is a moderately effective treatment for juxtapapillary and EP RCH. In this series, PDT resulted in tumour regression or stabilization as well as in the improvement of SRF and lipid exudation in all cases. However, stabilization or improvement of visual acuity was observed in only 50 per cent of the cases. The treatment benefits may be limited by pre‐existing macular changes and worsening of ERM. A larger prospective study is necessary to validate these findings.

Despite advances in the diagnosis and local tumor control, the overall mortality rate for uveal melanoma remains high because of the development of metastatic disease. The clinical and histopathological systems currently being used to classify patients are not sufficiently accurate to predict metastasis. Tumor genotyping has demonstrated significant promise but obtaining tumor tissue can be problematic. Furthermore, assessment of tumor tissue does not indicate whether tumor cells have actually been shed and cannot indicate whether treatment is reducing metastasis. The detection of circulating tumor cells in blood has been shown to be a prognostic biomarker that can be used to monitor the effectiveness of therapy in patients with metastatic carcinoma. Uveal melanoma disseminates hematogenously, and the detection of circulating melanoma cells may potentially be useful for diagnosis, risk stratification, and the monitoring of disease progression and treatment efficacy. PCR-based and immunomagnetic cell isolation techniques, derived from studies in patients with cutaneous melanoma, have been tested. For various biological and technical reasons, they have not demonstrated the accuracy and reproducibility required for an effective prognostic assay in patients with uveal melanoma. Assessments have been confounded by false positives and negatives and thus, correlations between circulating melanoma cells and survival have not yet been established. Circulating melanoma cell detection is a valuable tool for investigating metastasis in uveal melanoma and also has the potential to become a standard part of uveal melanoma management. However, more research on the biology of uveal melanoma as well as improvements upon the current technologies are needed.

No abstract