MicroRNA in refined diagnosis of choroidal melanoma

Epigenetic studies of the level of microRNAs in human oncogenesis indicate their signifi cant role in the development and growth of malignant tumors of various origins. The fi rst works on the role of microRNAs in patients with uveal melanoma appeared in 2008.The aim: to analyze the expression level of miRNA-126 and miRNA-223 in the plasma blood of patients and to determine their signifi cance in the refi ned diagnosis of choroidal melanoma. Materials and methods. We examined 84 patients with choroidal melanoma (CM), mean age – 63.4 ± 1.2 (35–86 y.o.). Localization – a single CM node with a thickness of 0.77–17.19 mm. The control group consisted of 28 volunteers, age – 62.9 ± 1.42 (45–78 y.o.). Plasma miRNA expression levels were determined by real-time PCR.Results. An increase in the level of expression of miRNA-223 and miRNA-126 in blood plasma was confi rmed in all 84 patients with choroidal melanoma N0M0 compared with the control group. An increase in the expression of miRNA-223 and miRNA-126 was proved with an increase in tumor prominence.Conclusion. The obtained results of an increase in the expression of miRNA-223 indicate an increase in cell proliferation, and an increase in the expression of miRNA-126 on the activation of angiogenesis in a growing tumor, which makes it possible to recommend a study of the level of miRNA-223 and miRNA-126 for a more accurate diagnosis of small CM in cases of difficulty of differential diagnosis with other tumor-like diseases of the choroid.

Brachytherapy in organ-preserving treatment of choroidal melanoma: complications and the possibility of their prediction

This review analyzed the domestic and foreign literature on brachytherapy of choroidal melanoma using ruthenium ophthalmic applicators. The review highlights the historical aspects of radiation treatment, from the first experience of using ionizing radiation in the treatment of malignant neoplasms to modern methods of brachytherapy; presents the radiobiological foundations of radiation therapy; considers the issues of radiation pathomorphosis, reflecting the nature of pathological changes in the choroidal melanoma tissue during brachytherapy; shows the dependence of the effect of exposure ionizing radiation from the phase of the cycle of cell division; and also describes the presence of changes characteristic of the response to ionizing radiation in unirradiated tissues. The analysis of various post-radiation complications, both early and late, was carried out in some detail, with emphasis on the possibility of predicting and preventing them in real clinical practice. A comparison is made in terms of the frequency of development of various post-radiation complications in the works of domestic and foreign authors, as well as a comparison with the effect of ionizing radiation from other radioactive isotopes. Recommendations of experts are given regarding the correct calculation of the dose to the sclera and medication support, based on many years of experience in the use of ruthenium ophthalmic applicators for brachytherapy of choroidal melanoma. The risks of developing such late complications as radiation maculopathy and radiation neuropathy have been demonstrated, especially in pre-equatorial tumor localization. The possibilities of modern methods of instrumental diagnostics for studying the processes occurring in the area of the tumor, as well as changes in the surrounding tissues, are shown, which determines the feasibility and importance of further study of this issue.

A Prediction Model to Discriminate Small Choroidal Melanoma from Choroidal Nevus

Objective: To develop a validated machine learning model to diagnose small choroidal melanoma. Design: Cohort study Subjects, Participants, and/or Controls: The training data included 123 patients diagnosed as small choroidal melanocytic tumor (5.0-16.0 mm in largest basal diameter and 1.0 mm to 2.5 mm in height; Collaborative Ocular Melanoma Study criteria). Those diagnosed as melanoma (n=61) had either documented growth or pathologic confirmation. 62 patients with stable lesions classified as choroidal nevus, were used as negative controls. The external validation data set included 240 patients managed at a different tertiary clinic, also with small choroidal melanocytic tumor, observed for malignant growth. Methods: In the training data, lasso logistic regression was used to select variables for inclusion in the final model for the association with melanoma versus choroidal nevus. Internal and external validation were performed to assess model performance. Main Outcome Measures: Predicted probability of small choroidal melanoma Results: Distance to optic disc ≥3mm and drusen were associated with decreased odds of melanoma whereas male versus female sex, increased height, subretinal fluid, and orange pigment were associated with increased odds of choroidal melanoma. The area under the receiver operating characteristic (AUROC) “discrimination value” for this model was 0.880. The top four variables that were most frequently selected for inclusion in the model on internal validation, implying their importance as predictors of melanoma, were subretinal fluid, height, distance to optic disc, and orange pigment. When tested against the validation data, the prediction model could distinguish between choroidal nevus and melanoma with high discrimination of 0.861. The final prediction model was converted into an online calculator to generate predicted probability of melanoma. Conclusions: To minimize diagnostic uncertainty, a machine learning based diagnostic prediction calculator can be readily applied for decision making and counselling patients with small choroidal melanoma.

Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5

AIM: To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and oridonin on choroidal melanoma cell lines, and to explore its underlying mechanism. METHODS: MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin, and MTT assay used to evaluate the inhibition rate of the two compounds on cells. Then, the cell cycle distribution and apoptosis were detected by flow cytometry, and changes in apoptosis-related proteins such as death receptor 5 (DR5), a-caspase-3, and x-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot. MUM-2B cells were transfected with si-DR5, which interfered with the expression of the DR5 gene. MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins. RESULTS: When TRAIL and oridonin were simultaneously administered to the MUM-2B cells, the apoptosis rate was significantly higher than that by the two drugs individually. However, the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone. Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells. The Western blot results showed that the protein expression levels of the DR5, a-caspase-3, and BAX increased, while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells. Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells. CONCLUSION: The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment, which may ascribe to up-regulation of DR5.

OCT-angiography for the diagnosis of radiation maculopathy in patients treated with proton beam therapy: A 2-year prospective study

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.