Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Important cytogenetic and genetic risk factors for the development of UM include chromosome 3 monosomy, mutations in the guanine nucleotide-binding proteins GNAQ/GNA11, and loss of the BRACA1-associated protein 1 (BAP 1). Most primary UMs are treated conservatively with radiotherapy, but enucleation is necessary for large tumours. Despite the effectiveness of local control, up to 50% of UM patients develop metastasis for which there are no effective therapies.Attempts to utilize the targeted therapies that have been developed for the treatment of other cancers, including a range of signal transduction pathway inhibitors, have rarely produced significant outcomes in UM. Similarly, the application of immunotherapies that are effective in cutaneous melanoma to treat UM have also been disappointing. Other approaches that have been initiated involve proteasomal inhibitors and histone deacetylase inhibitors that are approved for the treatment of other cancers. Nevertheless, there have been occasional positive outcomes from these treatments in UM. Moreover, combination approaches in UM have also yielded some positive developments. It would be valuable to identify how to apply such therapies efficiently in UM, potentially via individualized tumour profiling. It would also be important to characterize UM tumours to differentiate the potential drivers of progression from those in other types of cancers.The recent identification of novel kinases and metastatic genes in UM tumours makes the development of new UM-specific treatments feasible.
Accepted ArticleThis article is protected by copyright. All rights reserved A) Uveal Melanoma: Background and risk factors Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and represents ~5 % of melanoma diagnoses in the US annually [1-3]. UM originates from ocular melanocytes with 85% of cases arising from the choroid region and the remainder from the ciliary body and iris [4]. The prognosis in UM is poor, in particular because around 50% of patients develop metastatic disease. Hepatic metastases occur in up to 90% of individuals, followed by metastases in lung and bones, and after establishment of metastatic disease the median survival time is only 4-5 months [5]. At the time of diagnosis, systemic metastases are reported in only 3%of patients, but it is likely that micro-metastases have already developed in many cases [6,7].Currently there are no effective systemic drug therapies for primary or metastatic UM [8,9].The median age at diagnosis is 62 years and the incidence of UM in males and females, and whether there is right or left eye involvement, is similar [10]. Underlying risk factors for UM include melanocytosis, melanocytoma, neurofibromatosis and the presence of atypical nevi [11][12][13][14]. Race is also a significant risk factor with a 150-fold greater incidence in fair-skinned over dark-skinned populations [15]. The incidence of UM in European countries varies wi...
Purpose Radiation maculopathy (RM) is the leading cause of visual acuity (VA) loss after proton beam therapy (PBT) of choroidal melanoma. The aim of this study was to assess the value of optical coherence tomography-angiography (OCT-A) for the diagnosis of RM in patients with choroidal melanoma treated with PBT. Materials & methods This 2-year prospective, descriptive, single-center study included patients treated with PBT for choroidal melanoma. VA measurement, retinography, OCT and OCT-A were performed. Vascular density (VD) in the superficial capillary plexus (SCP), peri-foveal anastomotic ring changes and foveal avascular zone (FAZ) enlargement were studied. Results Nineteen patients were included in the study. The median baseline melanoma thickness was 5.7 [3.6–8.1] mm. The median melanoma-to-macula distance was 3.5 [2.6–4.6] mm. The earliest signs of RM identified on retinography were hard exudates developing at 12 [12–24] months, followed by retinal hemorrhages at 18 [12–30] months, found in 88.9% and 77.8% of patients respectively. On OCT, the earliest sign was the onset/progression of cystoid macular edema (CME) at 12 [6–12] months, found in 10 patients (52.6%). On OCT-A, 100% of patients presented with a discontinuity of the perifoveal anastomotic ring and a FAZ enlargement after 12 [6–24] months. After 12 months, a VD loss in the SCP by 11.7% and 10.8% compared to baseline, was found in the macular and foveal areas respectively. A significant negative correlation was found between the VA and the VD in the macular SCP (R = −0.43; p = 0.029). Conclusion OCT-A is a reliable and effective diagnostic tool for RM in patients with choroidal melanoma treated with PBT.
Background: Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples.Methods: A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n = 57) and
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