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This case report demostrates an unusual occurence of orbital metastasis along with liver metastasis 5 years following enucleation for ciliochoroidal melanoma with no extraocular extension. It exemplifies that metastasis of the tumour can occur in the ipsilateral orbit after enucleation. Importance of close clinical follow-up after enucleation for choroidal melanoma, careful socket examination, and regular systemic metastatic workup is demonstrated. To the best of our knowledge, this is the first case report of uveal melanoma with ipsilateral orbital metastasis.

A 47-year-old man presented with profound loss of vision in right eye and relative afferent pupillary defect. On fundus examination, posterior pole details were obscured due to dense vitreous haemorrhage. B-scan ultrasonography was performed that revealed a mushroom-shaped hyperechoic lesion with medium internal reflectivity on A-scan ultrasonography. After performing contrast-enhanced MRI of the orbit, a diagnosis of choroidal melanoma was established. Patient was managed using plaque brachytherapy based on multiplanar MRI. This was followed 10 months later by pars plana vitrectomy and cataract extraction. Vision postoperatively improved to 20/60. A systematic clinical assessment along with supportive ancillary investigations augments diagnostic accuracy and reduces delay in definitive management.

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.

BACKGROUND Despite being the most common intraocular malignancy among adults, choroidal melanoma is a rare cancer type, even more so when accompanied by lung cancer. We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy (CIRT). CASE SUMMARY A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye. During the examination, we found a right lung tumor that was histologically diagnosed as lung cancer. The patient was treated with CIRT for both malignant neoplasms. The CIRT dose was 70 photon equivalent doses (GyE) in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer. At 3 mo after CIRT, the choroidal melanoma completely disappeared, as did the right lung cancer 7 mo after; the patient was in complete remission. CONCLUSION CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

PURPOSE To assess outcomes of small and medium choroidal melanoma (less than 5.0 mm in height) following Iodine-125 episcleral brachytherapy. METHODS AND MATERIALS Patients with small and medium choroidal melanoma that underwent Iodine-125 brachytherapy with apical height of 1.0 mm to 5.0 mm and largest basal diameter of ≤16.0 mm were included. Data were extracted from the original dosimetry plans to determine doses to vision critical structures with the prescription point to the apical height (actual dose, ABS guidelines) and, after simulation, with the prescription point to the height of 5.0 mm (simulated dose, COMS protocol). Visual acuity (VA) outcomes with actual dose and that predicted with the simulated dose were estimated along with local recurrence, ocular survival, and survival at 5 years. RESULTS A total of 339 patients with a mean age of 61.5 years with a mean follow up duration of 43.4 months were included. The mean dose reduction for lens, optic disc, and fovea was 34%, 39.4%, and 41.4%, respectively with actual dose when compared with simulated dose. The Kaplan-Meier estimations for 3 year event free rate of VA of 20/50 or better were 56% and 31% for actual dose and simulated dose, respectively. Only 3 events of local recurrence were observed (enucleated) yielding 5 year local control and ocular survival rate of 98%. Overall survival (OS) and metastasis free survival (MFS) were 95% and 87.5% at 5 years, respectively. CONCLUSIONS Small and medium choroidal melanoma treated according to ABS has excellent outcomes. Brachytherapy planning using ABS guidelines as compared to COMS protocol may be associated with lower rates of radiation toxicity and vision loss.

Uveal melanoma is the most common primary intraocular tumor in adults and can have varying presentations, although it is frequently asymptomatic. One rare presentation of uveal melanoma is neovascular glaucoma (NVG). We present a case of a 20-year-old male who presented with 2 weeks of left eye redness and decreased vision who was found to have NVG. He was referred for evaluation of glaucoma. Fundoscopic and ultrasonographic examination revealed a mushroom-shaped choroidal mass with low internal reflectivity consistent with choroidal melanoma. The patient underwent enucleation, and metastatic workup revealed hepatic metastases. The patient died 18 months after initial diagnosis. This case emphasizes the importance of a complete ophthalmic evaluation in cases presenting with NVG of unclear etiology to exclude the presence of a potentially life-threatening intraocular tumor.

Purpose: to study angioarchitectonics of choroidal melanoma with varied biometric characteristics by comparing the results of indocyanine green angiography (IAG) and OCT angiography (OCTA).Material and methods. Angiography with indocyanine green and OCT angiography was performed in 45 choroidal melanoma patients (45 eyes, 20 men, 25 women, mean age 57.36 ± 15.11 years) to see the features of angioarchitectonics for various tumor elevations: up to 3 mm (small choroidal melanomas) and within the 3.1– 5.0 mm range (medium choroidal melanomas) and assess the informative value of the techniques.Results. We established a high diagnostic value of angiography with indocyanine green and OCT angiography in the diagnosis of vasculature of choroidal melanoma (89% and 71 %, respectively), an acceptable significance in small choroidal melanomas, and a higher informative value of angiography with indocyanine green in medium choroidal melanomas. The vasculature of small choroidal melanomas is characterized by type 1 angioarchitectonics predominance (59 %), while that of medium-sized melanomas corresponds to type 2 angioarchitectonics (81 %). The pattern match in angiography with indocyanine green and OCT angiography took place in 93.8 % of patients. The average depth of vessel identification during OCT angiography was determined to stay within the range of 186 μm for choroidal melanomas of up to 1.9 mm high, 220 μm for melanomas between 2 and 3 mm high, and 255 μm for melanomas higher than 3 mm.Conclusions. The use of contrast and non-contrast angiography in assessing the vasculature of choroidal melanoma is highly informative and useful for the assessment of the type of angioarchitectonics. The use of OCT angiography is more informative for tumors with an elevation of up to 3 mm. In order to increase the accuracy and effectiveness of OCTA, the identification of newly formed vessels should be carried out with regard to the parameters established.

Purpose To report a case of a woman diagnosed with choroidal melanoma during pregnancy, as well as review similar cases published in the literature. The prevalence, risk factors, treatment, prognosis, and outcomes of choroidal melanoma in pregnancy are addressed. Methods An extensive search of the literature was conducted by accessing PubMed, MEDLINE, and Scopus databases in January 2018 to identify cases of choroidal or uveal melanoma diagnosed during pregnancy. Patient A 37-year-old white woman pregnant with twins and diagnosed with choroidal melanoma. Results Choroidal melanoma in pregnancy has a prevalence ranging from 4.3% to 7.5% among women of childbearing age with the disease. Pregnancy has been linked to increased incidence of choroidal melanoma, but female hormones have not been shown to play a role in the pathogenesis of the disease. Other factors such as melanocyte-stimulation hormone and fetal-induced angiogenesis may be implicated. Choroidal melanoma in pregnancy has not resulted in a worse maternal or fetal outcome. Conclusion Although rare, choroidal melanoma in pregnancy is a clinical challenge. Management of these patients should be tailored to maternal and fetal needs.

Nodular posterior scleritis (NPS) is rare; however, it is critical to differentiate it from similar intraocular pathologies to prevent inappropriate and potentially irreversible treatment. Multimodal imaging is beneficial in the diagnosis of NPS. This report describes the diagnosis and management of a case of NPS with corticosteroid therapy that led to complete resolution.

49-year-old male presented with an eight-month history of gradual blurring of vision of the left eye accompanied by eye pain, left-sided headache, eye redness, gradual proptosis and opacification of the cornea. Ocular ultrasound revealed a homogenous echodensities with moderate echogenicity and intermittent loculation occupying the whole vitreous cavity. Chest CT-scan with contrast showed multiple nodules on both lung fields evident of metastasis

Purpose The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (106Ru) plaque to treat uveal melanoma. Material and methods A literature review was performed based on results from searching PubMed, Embase, Web of Science, Scopus, and Cochrane databases, using the following key words: "choroidal melanoma", "uveal melanoma", "brachytherapy", and "ruthenium-106". We included studies performed on more than 30 patients since 1986, reporting on local control rate, complications rate, mean radiation dose, and mean tumor thickness. The cumulative analysis was performed using Metaprop command of Stata v.16, and meta-regression was conducted based on mean tumor thickness and mean radiation dose to tumor's apex. Results Twenty-one retrospective studies were selected, involving 3,913 patients treated primarily with 106Ru plaque brachytherapy. The range of radiation dose to tumor apex was from 70 Gy to 250 Gy. The local control rate following brachytherapy ranged from 59% to 98%, and the overall weighted mean of local control was 84%. However, the heterogeneity between studies' reports was remarkable (I2 = 95.40%). Meta-regression based on tumor thickness and mean dose of radiation to the apex showed that the studies' heterogeneity was minimally related to the difference in mean tumor size (I2 = 92%). The correlation between larger tumor size and lower local control rate was statistically significant (p-value = 0.024). There was no significant correlation between the mean radiation dose and local control rate (p-value = 0.679). The most commonly reported complications were cataract and radiation-related retinopathy. Conclusions Although the studies' heterogeneity was high, in a prescription dose ranging from 70 Gy to 250 Gy to the tumor apex, 106Ru brachytherapy seems to be successful in local control of uveal melanoma. The efficacy of 106Ru in controlling uveal melanomas decreased with the increase in tumor thickness. However, these outcomes should be verified in randomized comparative studies.

MicroRNAs (miRNA, miR) - regulate gene expression, take part in the regulation of cell life, proliferation and apoptosis. There are not enough publications on the study of microRNA in the plasma of patients with choroidal melanoma (CM) and the presented data are contradictory. An increase in the level of microRNA-146a in blood plasma was noted in patients with cancer of the lung, esophagus and breast. In the present study, we used microRNA-146a in the blood plasma of patients with CM. Purpose. To determine the possibility and reliability of detecting microRNA-146a in the blood plasma of patients with CM, taking into account the localization of the tumor and its size. Material and methods. The blood plasma of 84 patients was studied mean age 63.4±1.2 years. A control group of 28 people who did not have tumor or chronic autoimmune diseases mean age 63.25±1.43 years. The expression level of miRNA-146a was determined by quantitative PCR. Results. An increase in the level of microRNA-146a was shown, which correlates with the localization and thickness of the tumor. The results were confirmed by statistical analysis. Conclusion. MicroRNA-146a, which increases in plasma levels in patients with CM as its size increases, can be used as a biomarker of aggressive tumor course in terms of hematogenous metastasis. Key words: choroidal melanoma, microRNA-146a, biomarkers.

Choroidal melanoma has been described in literature as “a complex and evolving story” which is not far from the reality. While the incidence of this deadly disease is lower in the Asian population in general, the severity of symptoms and lack of cost affordable strategies to manage a case with extensive metastasis are lacking. Therefore, it should be our primary objective as ophthalmologists to diagnose and manage the primary malignancy at the earliest and to persuade the patient for frequent follow ups. Uveal melanoma is the most commonly found primary intraocular tumour in adults.1 Out of the three varieties, choroidal melanoma accounts for 80 % of all uveal melanoma. It is more commonly found in Caucasians and in middle aged males2 with a predilection for tropical areas with high levels of solar radiation.3 The incidence of uveal melanoma in Asian and African population is 0.15 - 0.18 and 0.2 - 0.4 per million respectively which is lowest in the world.4 Its origin can be attributed to the melanocytes or melanin-containing cells found in uveal tissue and important predisposing factors include lighter skin tone and eye colour. Shah et al5 also stated that UV exposure due to arc welding is also a risk factor. Around one fourth of all cases maybe asymptomatic. Presentation as secondary angle closure glaucoma is rare. Othman et al6 found this rare presentation in eight cases all of whom required enucleation. In fact, glaucoma as an initial manifestation of uveal melanoma has been seen in only 3 % of all cases.7 Collaborative ocular melanoma study (COMS) was one of the largest multicentric randomised trials with 1302 subjects detailing demography of patients, classification as well as a comparative evaluation of its treatment modalities. It paved the way for the current standard of care in treating ocular melanomas. This study showed the growth patterns of small sized tumour and demonstrated that there was no significant difference in long term survival rates in patients treated by enucleation and those treated by brachytherapy.8 Although considered a landmark it did not take into account the doubling time for this aggressive malignancy nor did it account for micro metastasis not easily detectable at the time of presentation of primary tumour. There was also a lack of data regarding iris and ciliary body melanomas.9 In this respect the TNM classification of uveal melanoma is more comprehensive, if not complex. The main treatment modalities are radiation therapy and surgical removal of local tumour which range from the fairly simpler enucleation and exenteration to the more challenging endo-resection, exo-resection, transscleral or transretinal resection. The treatment of metastasis is less satisfactory and includes either resection of regional metastasis or hepatic intraarterial chemotherapy or hepatic perfusions. None of which have shown to have good long-term survival.10,11,12

Purpose: To describe a clinical case of atypical posterior scleritis mimicking an amelanotic choroidal melanoma. Method: Observational case report of a 54-year-old woman who presented to the emergency department with photophobia and blurred vision in her left eye for three days. The development of a raised hypopigmented lesion superior to the papilla with choroidal folds and without vitritis simulated an amelanotic choroidal melanoma. Differential diagnosis took into consideration other compatible entities, including choroidal masses or orbital pseudotumor. Results: The patient was subject to full clinical examination, laboratory test, optical coherence tomography, orbital echography, and magnetic resonance imaging. Treatment with oral prednisone showed a significant improvement in all clinical and anatomical parameters. Discussions: Posterior scleritis is characterized by great clinical variability and sometimes can simulate an amelanotic choroidal melanoma. Performing an appropriate differential diagnosis of a large amelanotic lesion is the most important point during a routine ocular examination due to the implications for the patient. Conclusions: Posterior scleritis is a rare and incompletely understood inflammatory disease that affects the posterior part of the sclera. It can be associated with a range of conditions and very often is underdiagnosed. In about one third of the cases, it is related to some systemic disease, especially to autoimmune entity, so it may require a multidisciplinary approach. This case highlighted the importance of a solid differential diagnosis and an early treatment in order to help prevent the appearance of complications that can limit not only the visual outcome of the patient but even his survival in the most extreme cases. Abbreviations: LE = left eye; RE = right eye; BCVA = best corrected visual acuity; BO = both eyes; IOP = intraocular pressure; OCT = optical coherence tomography; MRI = Magnetic Resonance Imaging

Purpose To compare tumor control, vision, and complications between patients with a choroidal melanoma of Design Retrospective, comparative case series. Participants One hundred sixty-four consecutive patients with a choroidal melanoma of Methods Diagnosis was based on growth or high-risk characteristics. The apical dose was 100 to 120 Gy aiming to deliver ≥250 Gy to the sclera. Plaque positioning was modeled retrospectively. An increase of ≥0.3 mm in thickness and ≥0.5 mm in LBD indicated local recurrence. Outcomes were compared with cumulative incidence analysis and Cox regression. Median follow-up time for patients still alive was 8.4 years. Main Outcome Measures Recurrence rate, low vision, blindness, radiation maculopathy, and optic neuropathy. Results Melanomas treated with the 10-mm plaque were smaller (median thickness, 1.9 mm vs. 2.6 mm; LBD, 7.1 mm vs. 8.6 mm) and located closer to foveola (median, 2.0 mm vs. 2.8 mm) than those treated with the 15-mm plaque (P Conclusions The 10-mm ruthenium plaque contributes to better visual preservation, particularly with tumors close to fovea, without increase in local recurrence rate, and may therefore be preferable to the 15-mm plaque.

Purpose: To provide real-world data on the world-wide-web for patient and doctor awareness. Methods: From December 2017 to January 2020, consecutive patients with choroidal melanoma (CM), iris ciliary body melanoma (ICM), and ocular surface squamous carcinoma (OSSC) had specific outcomes recorded at each return visit. Each result was anonymized, entered in an online portal, and sent to a unique software program where it was used to create real-world data of number of patients, mean vision, local tumor control, eye salvage, systemic metastases, and length of follow-up for our eye cancer center. Results: A HIPAA compliant, internet-based software program was developed and linked to public access web page to collect and analyze near-real-time data pertaining to the treatment, vision, life, and follow-up time of patients. During this period, CM radiation plaque tumor control was 99.7%, median vision 20/25 (mean 20/50) and eye salvage 95.8%. ICM tumor control was 99.1% and the median vision 20/20 (mean 20/20). OSSC tumor control was 100% and the most common vision was 20/20 (mean 20/25). Rates of primary enucleation as treatment were 4.2% for CM, 2.8% for ICM, and 0% for OSSC. All patient results were updated by the ophthalmic oncology fellow at each patient visit as to reflect near-real-time outcomes at our center. Conclusion: Prospective data collection of returning patients was found to be a simple method to reflect patient care outcomes. This method of reporting doctor outcomes offers a measure of transparency for patients and an opportunity to compare results with other clinical practices.

Purpose: The aim of the study was to evaluate equivalence of growth rate and pathologic confirmation in small choroidal melanoma (SCM). Design: This study is a case series. Subjects, Participants, and Controls: A total of 61 patients with a choroidal melanocytic tumor of size 5.0–16.0 mm in the largest basal diameter and 1.0–2.5 mm in thickness were classified into the pathology-confirmed group (n = 19), growth-confirmed group (n = 30), and with combined observations (n = 12). Methods: Distribution of clinical variables (age, gender, laterality, tumor dimensions, tumor location, and presence of orange pigment, subretinal fluid, drusen, and retinal pigment epithelial [RPE] atrophy) between the groups was analyzed. Patient and disease characteristics were summarized as the median and interquartile range for continuous variables and the frequency and percentage for categorical variables. Comparisons were made using the Wilcoxon rank sum test for continuous variables and either Fisher’s exact test or the χ2 test for categorical variables with a p value threshold of 0.05 for statistical significance. Growth rate (change in basal dimension/12 months) diagnostic of SCM was quantified. Main Outcome Measures: The primary aim of this study was to test the hypothesis that “growth” was diagnostic of SCM with the secondary aim of quantifying the malignant “growth rate” (growth rate of SCM). Results: The clinical characteristics among all 3 groups were similar except more patients with symptoms (68 vs. 20 vs. 42%, p = 0.004) and juxtapapillary location (p = 0.03) were in the pathology group than in the growth-confirmed group. Those in the combined and growth-confirmed groups had more patients with drusen (11 vs. 60 vs. 50%, p = 0.003) and RPE atrophy (11 vs. 23 vs. 67%, p = 0.003), respectively, than in the pathology group. The median time to detect growth was 9 months (range 3–26 months). The mean growth rate in basal dimension was 1.8 mm/12 months (range, 0.0–7.4 mm; [95% CI: 1.32–2.28]). Conclusions and Relevance: Choroidal melanocytic lesions exhibiting a defined growth rate can be clinically diagnosed as SCM without a need for biopsy.

Optic nerve head melanocytoma is a benign pigmented lesion which is generally asymptomatic, however it can sometimes be related with visual field disturbance. In most cases the tumor stays stable for the duration of the life. Rarely 1-2% of such cases undergo a malignant transformation, hence serial monitoring is necessary. We report an instance of optic nerve head melanocytoma in a 30-year-old male with characteristic imaging signatures. Keywords: Optic nerve head, Melanocytoma, Choroidal melanoma

Описывается редкое наблюдение одиночного гигантского метастаза веретеноклеточной меланомы хориоидеи в печень у молодой женщины, которая восемь лет назад, в возрасте 32 лет, перенесла энуклеацию левого глаза по поводу первичной опухоли. Патология печени установлена во время ультразвукового исследования на восьмом месяце беременности, которая была подтверждена во время кесарева сечения. После родоразрешения пациентка направлена в онкологический диспансер, где метастаз меланомы подтвержден гистологически на основании транскутанной пункционной биопсии. Проведены пять курсов химиотерапии без эффекта. Пациентка госпитализирована в отделение портальной гипертензии областной больницы. При тщательном онкологическом обследовании установлен солитарный характер метастаза. Его объем достигал 2338 см3, неизмененной паренхимы – 951 см3. Также проведено детальное изучение ангиоархитектоники печени на основании данных МСКТ-ангиографии и инвазивной селективной целиакографии. Периферические ветви правой печеночной артерии деформированы, фрагментированы с заметной перекалибровкой – злокачественный процесс. Артериальные сосуды левой доли не изменены. Париетальные разветвления прослеживаются на всем протяжении. Правая и срединная вены полностью вовлечены в процесс, левая печеночная вена интактная. Учитывая неэффективность адъювантной терапии, прогрессирование заболевания, выполнена правосторонняя гемигепатэктомия. Ранний послеоперационный период протекал без осложнений. Осмотрена через один год и десять месяцев: качество жизни хорошее.

Recently published experimental data on the presence of different types of angiotensin receptors in melanoma tissue and in breast cancer, for example, are undoubtedly alarming and indicative because Sartan therapy (in certain groups of patients) may be a risk factor for the patients themselves. The reason for this is the ability of the specific group of drugs to promote carcinogenesis by blocking certain types of receptors, presented in certain types of tumors. The available in vivo and in vitro data in the world literature on the influence of antihypertensive drugs (Sartans and Thiazide diuretics) on melanogenesis and development of other cancerous forms, although disputed, are numerous. Even more disturbing are the further data in the medical literature on the development of multiple tumors after administration of Sartans alone or in combination with hydrochlorothiazide. According to other literature data, even monotherapy with the already mentioned diuretic- hydrochlorothiazide, could be seen as a possible key or risk factor for the development of cutaneous melanoma. We present a clinical case of a 67-year-old patient with anamnestic data for systemic antihypertensive therapy with a combined preparation containing Valsartan / hydrochlorothiazide 160 mg / 12.5 mg for the period from the end of 2011 to March, 2020, came on occasion of a prophylactic dermatological examination. The examination found a pigmented lesion in the right torso, clinically and dermatoscopically suspected of thin cutaneous melanoma. According to the anamnesis and available documentation, it is clear that within this combined antihypertensive medication, the patient has developed two additional neoplasms in the recent past: choroidal melanoma and colorectal carcinoma successfully treated surgically. To what extent, the shared data (on the occurrence of multiple tumors after combination treatment with antihypertensives such as sartans and thiazide diuretics) would lead to the necessary and desirable rethinking of therapeutic strategies for the treatment of hypertension and clarification of the mechanisms at molecular level, at this moment - remains unclear. But in practice it should be highly recommended. Keywords: Melanoma; Melanogenesis; Antihypertensive Therapy; Valsartan; Sartans; Surgery; Hydrochlorothiazide

ZusammenfassungUlzerationen der unteren Extremität sind ein häufiger Vorstellungsgrund in der phlebologischen Sprechstunde. Dementsprechend können dem phlebologisch tätigen Arzt neben gängigen Differenzialdiagnosen wie dem venösen, arteriellen und gemischten Ulkus auch weniger häufige, mit Ulzerationen assoziierte Krankheitsbilder begegnen. Eine sorgfältige Anamnese und eventuelle Umfelddiagnostik sind neben der sonografischen Untersuchung essenziell.Wir berichten über einen 77-jährigen Patienten, der vom Hausarzt zur Abklärung von vor 3 Jahren aufgetretenen Ulzerationen am Oberschenkel vorgestellt wurde.Die vorliegende Kasuistik beschreibt die differenzialdiagnostische Aufarbeitung, an deren Ende die Ulzerationen am Oberschenkel, ursprünglicher Grund der Vorstellung, als ulzerierte Granulome im Rahmen der bekannten Sarkoidose diagnostiziert wurden. In den Vordergrund der ausführlichen Umfelddiagnostik geriet allerdings das Aderhautmelanom mit multiplen Metastasen-verdächtigen Befunden insbesondere im Gehirn und pulmonal.Bedauerlicherweise verstarb der Patient unerwartet kurz vor Abschluss der Diagnostik und vor der Einleitung einer spezifischen Therapie aufgrund einer akuten Einblutung in einen Metastasen-verdächtigen zerebralen Rundherd.

Purpose To evaluate why small- and certain medium-sized parapapillary choroidal melanoma (pcM) patients treated with hypo-fractionated proton therapy (PT) retain excellent long-term visual acuity (VA) and assess the negative predictive factors for retaining good vision (≤ 0.2 logMAR (≥ 0.6 decimal) after 5 years. Methods This single-center, retrospective, comparative study recruited consecutive pcM patients that were treated with PT. Between 1984 and 2005, 609 patients received a total of 60 CGE, of whom 310 met the following inclusion criteria: posterior tumor border ≤ 2.5 mm from the optic disc, largest tumor diameter ≤ 17.9 mm, tumor thickness ≤ 5.2 mm and available follow-up data for at least 5 years. Results Mean follow-up was 120.8 ± 48.8 months (54.0–295.0). Out of 310 patients, 64 (21%) maintained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years following PT and were allocated to the “good visual outcome” (GVO) group, while the remaining 246 (79%) constituted the “poor visual outcome” (PVO) group, subdivided into 70 (22%) with a VA of 0.3–1.0 logMAR (0.1–0.5 decimal) and 157 (57%) patients with a VA > 1.0 logMAR (P = 0.04), tumor localization ≤ 0.5 mm to the fovea (P P = 0.02 and P Conclusions Of 310 small- to medium-sized pcM patients successfully treated with PT, 21% retained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years. Strongest negative predictive factor for retaining good long-term vision was the volume of the macula irradiated with at least 30 Gy.

The aim of this study was to assess the diagnostic ability of N-isopropyl-p-[I-123] iodoamphetamine (IMP) SPECT semi-quantitative evaluation based on the standardized uptake value (SUV) in patients with choroidal melanoma. The secondary aim was to investigate the 6-h IMP SPECT imaging in comparison with 24-h imaging. Twenty-five patients (14 males and 11 females, mean age of 59.2-year-old) were analyzed in this retrospective study. Patients underwent 24-h IMP SPECT imaging with a gamma camera after intravenous injection of IMP. Twelve of 25 patients underwent 6-h SPECT imaging in addition to the 24-h imaging. All acquired SPECT images were fused with CT images using an image-analysis software. To assess the utility of semi-quantitative evaluation method, we introduced an image evaluation method using SUVmax comparing with conventional count-based uptake index (UI) evaluation of the lesion. Volumes-of-interest (VOIs) for SUVmax and regions-of-interest (ROIs) for UI were drawn referring to the SPECT-CT fusion image. Then the relationship between the 6- and 24-h images was examined both in SUV and UI evaluation. Furthermore, the relationship between the size category classification (SCC) by UICC/AJCC: 1–4 scales and each semi-quantitative value using SUVmax and UI was also assessed. SUVmax of the tumor was significantly higher than that of the normal side; 2.37 ± 0.88 and 1.77 ± 0.39 (P

Purpose: To study the features of small choroidal melanoma and choroidal nevi angioarchitectonics using the optical coherence tomography angiography (OCTA).Patients and methods. We examined 128 patients with small choroidal neoplasms: 41 — with small choroidal melanoma (group 1), 42 — with suspicious nevi (group 2) and 45 — with benign nevi (group 3). All patients underwent general ophthalmic examinations and special instrumental diagnostic methods (ultrasound examination (US), fluorescence angiography (FA), spectral optical coherence tomography (SOCT), OCTA).Results. OCTA in all patients with small choroidal melanoma showed neovascular network under retinal pigment epithelium. We found a looped, cranked-twisted, heterogeneous vascular network with uneven clearance and with numerous bends and weaves, located under the vessels of retina. The limiting avascular zone corresponding to the tumor slope was determined in 19 (46.3 %) of 41 cases. There was a rim of dilated hyperreflective choriocapillaries on the periphery of the tumor. We identified hyperreflective homogeneous enlarged choriocapillaries in the focus area with a brighter glow than the surrounding choriocapillaries in 39 (92.9 %) of 42 patients with suspicious choroidal nevus. We detected an avascular zone with surrounding extended hyperreflective choriocapillaries in the center of the nevus in 3 (7.1 %) of 42 cases. We diagnosed homogeneous isoreflective choriocapillaries similar in brightness to the surrounding vessels in all 45 patients with benign nevi.Conclusions. Thus, the complex of clinical and instrumental methods, including OCTA, makes it possible to establish the diagnosis of malignant tumor of the choroid in early stages. At the same time, OCTA: 1) allows to visualize of the tumor vessels in the choroidal layer in 100 % of cases of in small choroidal melanoma; 2) makes it possible to distinguish the newly formed tumor vessels from the choriocapillaries in case of small choroidal melanoma; 3) provides an opportunity to establish the correct diagnosis and provide timely assistance to patients with benign and malignant choroidal tumors.

Purpose:This work assesses longitudinal microvascular changes in eyes treated with iodine-125 episcleral plaque brachytherapy (EPB).Methods:High-resolution optical coherence tomography angiograms (OCTAs) of the central 3 × 3-mm macula were obtained from iodine-125 EPB–treated and untreated fellow eyes of 61 patients. Previously validated semiautomated algorithms quantified capillary density (vessel skeleton density [VSD]) and caliber (vessel diameter index). Nonperfusion was also quantified as flow impairment region (FIR). Examinations from treated and fellow eyes obtained before treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps evaluated spatial correlation between radiation dose and microvascular metrics.Results:At 6 months, treated eyes had significantly lower VSD (0.145 ± 0.003 vs 0.155 ± 0.002; P = .009) and higher FIR (2.01 ± 0.199 vs 1.46 ± 0.104; P = .01) compared with fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. Vessel diameter index was significantly higher in treated eyes than in fellow eyes at 2 years (2.92 ± 0.025 vs 2.84 ± 0.018; P 45 Gy) radiation to the fovea and noted significant differences in VSD and FIR between groups.Conclusions:OCTA can quantify and monitor EPB-induced retinopathy and can detect vascular abnormalities even without clinically observable retinopathy. OCTA may be useful in investigating treatment interventions aiming to delay EPB-induced radiation retinopathy.

A retrospective analysis of the immediate and long-term effectiveness of the treatment of the choroidal melanoma using transpupillary thermotherapy (TTT) was carried out. The study included 84 patients with choroidal melanoma (C69.3) who received treatment between 2007 and 2018. Patients were sampled from the Belarusian Cancer Register. The average values of the thickness of the tumor were 2.6±1.3 mm, the diameter of the base - 7.2±3.3 mm. TTT was carried out using a diode laser with a wavelength of 860 nm and radiation power of 200 - 800 mW, the exposure time was 60 s, and the diameter of the laser spot was varied between 1 and 3 mm. The entire surface of the tumor was thermally treated with overlapping fields from the periphery to the top. 75 patients underwent a single session of TTT, while 9 - two sessions with an interval of 3–4 weeks. As a result of the treatment, 51 (60.7%) patients showed complete tumor resorption, 28 (33.3%) patients had stabilization of the tumor process, and 5 (6.0%) patients had no effect. In the group of patients with stabilization of the tumor process, continued growth was recorded in 16 (19.1%) patients with follow-up periods of 3 months to 4 years. In 19 (37.3%) patients from the group with complete tumor regression, relapse was observed 1 to 8 years after TTT. Metastatic disease (disease progression) developed in 5 (5.9%) patients, of which in 1 patient during the first 12 months, in 1 patient - after 4 years, and in 3 patients more than after 5 years of the follow-up observation. Analysis of the effectiveness of TTT of choroidal melanoma showed that an increase in the thickness and diameter of the base of the tumor focus results in the decrease of immediate effectiveness, and the rise of the likelihood of continued tumor growth.

To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic neuropathy, radiation-induced retinopathy, iris neovascularization, secondary glaucoma, enucleation, and local tumor control after proton beam therapy (PBT) of choroidal melanoma. Retrospective analysis of 1129 patients, who received primary PBT for the treatment of choroidal melanoma with a dose of 60 cobalt gray equivalents (CGE) between 1998 and 2013 at the Helmholtz-Zentrum Berlin, Germany. Kaplan-Meier curves and logrank test have been used for time-to-event analyses. Adjustment for potential confounders was done using multiple Cox regression models with forward and backward selection. We found a significant correlation between the irradiated length of the optic nerve and the dose to the optic disc (correlation coefficient, 0.93). Multivariate Cox regression revealed the dose to the optic disc as an independent predictive risk factor for the development of radiation-induced optic neuropathy (p < 0.001, HR 1.023, 95 CI 1.016–1.029), iris neovascularization (p < 0.001, HR 1.013, 95% CI 1.008–1.019), secondary glaucoma (p < 0.001, HR 1.017, 95% CI: 1.011-1.023) and enucleation (p < 0.001, HR 1.037, 95% CI 1.020-1.053). The irradiated length of the optic nerve was not a statistically independent predictive risk factor in multivariate analysis. Our data implicate the predominance of the dose to the optic disc over the irradiated length of the optic nerve regarding radiation-induced optic neuropathy, iris neovascularization, secondary glaucoma, and enucleation.

It is known that 25% of choroidal nevus are suspicious, and the risk of their malignanisation is 2-13% with a tendency to increase during follow-up me elongation. It is known that 5.8% undergoes malignancy within 5 years, and 13.9% of suspicious choroidal nevi undergoes malignancy within 10 years. In the article, a clinical case of choroidal melanoma development 5.5 years after the detection of suspicious nevus in a patient who refused to follow up is described. In the presented case, there was a combination of two risk factors of nevus malignisation, which significantly increases the likelihood of such an outcome. Long-term follow-up of patients is required from the first day of diagnosis nevus of the choroid with signs of progression.

Purpose. Estimation the local efficacy of the combined treatment — brachytherapy (BT) with laser coagulation (LC) in choroidal melanomas of juxta and parapapillary localization in the long-term follow-up. Patients and Methods. In 2009–2013, 50 patients with choroidal melanoma of juxta and parapapillary localization were examined and treated, 32 women and 18 men aged from 32 to 76 years old (average — 53.8 ± 9.6 years). The averaged tumor height was 3.8 ± 1.3 mm, basal diameter — 11.2 ± 2.4 mm. The combined organ-preserving treatment included a LC from the optic disc with subsequent BT was performed. The indications for this method were choroidal melanomas of juxta and parapapillary localization (the distance between the optic disc and the central border of the tumor was no more than 1.5 pd), with the absence of subretinal exudate and retinal detachment in this zone. The follow-up period after the combined treatment ranged from 18 to 102 months (Me = 60 months). Results. Complete tumor resorption was achieved in the majority — 38 (76.0 %) of cases, partial — in 11 (22.0 %) patients, stabilization of the process — only in one (2.0 %) patient, continued growth was not observed in any patient. The initial size of melanoma in patients with complete and partial tumor resorption showed similar averaged values, amounting to 3.8 ± 1.3 mm and 3.6 ± 1.1 mm (p > 0.05), respectively, basal diameter — 11.1 ± 2.4 mm and 11.4 ± 2.4 mm (p > 0.05), respectively. According to the duplex scanning, an increase in the distribution density of bloodflow in the projection of the tumor focus was noted compared with the initial data. In the spectral Doppler flow analysis study, an increase in the linear characteristics of the blood flow in the tumor’s own vessels after LC was recorded. Complications included optic neuropathy (88 %), hemorrhage (36 %) and secondary glaucoma (6 %). Conclusions. The combined treatment allowed to achieve high therapeutic results — 76.0 % of the total resorption of choroidal melanomas, which have unfavorable localization for BT. Given the main focus of local treatment of the choroidal melanoma on its destruction, this technique can be used to increase the effectiveness of the BT of choroidal melanomas of juxta and parapapillary localization.

Choroidal melanoma is the most common and life-threatening intraocular malignant neoplasm affecting the eye choroid in about 90 % of cases. The incidence varies from 0.7 to 1.1 per 100,000 of the population. This category of malignant neoplasms is highly aggressive in terms of local distribution, the occurrence of loco-regional and distant metastases. According to various authors, the frequency of metastasis reaches up to 50 %, the risks of metastatic disease depend on the size of the tumor, the duration of observation, clinical and pathomorphological characteristics of the choroidal melanoma and genetic factors. This article provides a detailed literature review on the developmental aspects and growth dynamics of choroidal melanoma from the point of view of neoangiogenesis and the phenomenon of vasculogenic mimicry, and the possibilities of instrumental diagnostics for determining the malignant vasculature of a tumor. The relevance of studying this issue is determined by the peculiarities of the origin of choroidal melanoma, which can occur both de novo and due to malignant transformation from nevus cells and the critical point for it is a tumor thickness of more than 2 mm, at in which the the process of neoangiogenesis starts. This review details the role of various methods of instrumental diagnostics, such as doppler ultrasound imaging to determine the presence or absence of blood flow in the tumor and its blood flow characteristics, angiography using contrasts: fluorescein and indocyanine green angiography, and optical coherent tomography—angiography to identify the malignant vasculature and evaluation of tumor angioarchitectonics. It has been shown that in the diagnosis of especially small choroid melanomas, which are of significant diagnostic complexity, a multimodal approach using the above research methods is important. There is no doubt that these instrumental technologies aimed to identify the malignant vasculature of choroidal melanoma play a large role not only in diagnosis, but also are of considerable practical interest in planning treatment, in assessing its effectiveness, and also in predicting the risks of metastatic process development.

Background Uveal melanoma is the commonest intraocular malignant tumor in adults and the choroid is the commonest involved location. It is more prevalent in Caucasians; however, the demographics are widely variable based on ethnicity. Histopathological features have been correlated to the cytogenetic profile, which we intend to report through the study of enucleated eyes with choroidal melanoma (CM). Materials and Methods A retrospective review of 28 enucleated globes with CM in 2 tertiary eye centers (January 2000-December 2017). The tumors were histopathologically classified based on the 8th edition of the American Joint Committee on Cancer (AJCC). The histopathological risk factors and the AJCC classifications were correlated with Fluorescence in situ hybridization (FISH) for chromosomes 3 and 8 available results in 18/28 eyes. Results We have included 28 patients with a mean age of 56 years, 13 males (46.4%) and 15 females (53.6%). None had lymph node involvement or metastatic disease. The tumor size was categorized as 3 and 4 in 68% of eyes. Half tumors were of spindle cell type and were associated with absent cytogenetic abnormality in chromosomes 3 and 8 (P=0.005). Closed vascular loops presence was significantly associated with abnormal chromosomes 3 and 8 (P=0.027). Conclusion Patients in our area presented late with larger tumor size. The spindle cell CM was the commonest and correlated with negative FISH results, while the presence of closed vascular loops was a risk factor for abnormal FISH results hence expected worse prognosis. AJCC classification did not correlate well with our FISH results., Highlights • Spindle cell type was the commonest in 28 enucleated globes with choroidal melanoma. • Mean age was 61 years with slight female predominance in 54%. • Large tumors (AJCC category sizes 3 and 4) were seen in 68% due to late presentation. • Absent chromosomes 3 and/or 8 abnormality was significantly associated with spindle cell type (P=0.005). • Chromosomal abnormality (3 and/or 8) was significantly associated with closed vascular loops (P=0.027).

Background: To report a case of autologous corneal transplant in a patient with corneal leukoma and choroidal melanoma in the fellow eye. Case Presentation: A 56-year-old woman was complaining about decrease in vision in her left eye. The patient was on the waiting list for a corneal transplant on her right eye due to corneal leucoma after a previous herpes infection. The patient was diagnosed with choroidal melanoma in her left eye. Due to the tumor size (longitudinal diameter >10 mm; anterior-posterior diameter >16 mm) the patient decided to undergo enucleation, after being informed about different treatment options (brachytherapy and enucleation). The patient showed her willingness to use the cornea of the left eye as a transplant for her right eye. After discussion with the ethical committee and its approval, and signing informed consent, the patient underwent enucleation of her left eye. The sample was examined by a pathologist and found to be free of melanoma cells in the corneolimbal tissue. Afterwards, trepanation of the donor cornea button was performed and transplanted to the left eye. Conclusion: Autologous corneal transplantation is a safe and feasible procedure in selected cases.

BACKGROUND: Diagnosis of small choroidal melanoma is mainly based on tumour thickness, subretinal fluid, or lipofuscin pigment. Ultra-wide-field imaging (UWF) allows depiction of choroidal lesions through a red (RC) and a green channel (GC). Aim of the study was to determine the utility of this tool in the detection of small choroidal melanoma. METHODS: Retrospective cross-sectional study of patients with small choroidal pigmented lesions up to 3 mm in thickness. All patients underwent clinical and imaging assessment including UWF. Lesions were subcategorized based on thickness and lesion type. A qualitative assessment ensued using the red and green channels feature. RESULTS: A total of 152 patients were included. Melanotic naevi (76/152,50%) and small choroidal melanomas (55/152,36%) were the predominant types. Thickness was

PURPOSE The aim of this study was to evaluate retinal microvascular abnormalities following plaque radiotherapy of choroidal melanoma (CM) using wide-field swept-source optical coherence tomography angiography (OCTA). DESIGN Single-centre retrospective review. METHODS Retrospective case series of 105 CM patients treated with I-125 plaque radiotherapy and imaged with wide-field (15 × 9 mm) SS-OCTA from March 2018 to August 2018 at the Ocular Oncology Service, Wills Eye Hospital (Philadelphia, PA). RESULTS At mean follow-up of 49 months (range 4-297) after plaque radiotherapy, there were 52 eyes (50%) with clinically evident radiation retinopathy (CERR) and 53 eyes (50%) without CERR. Comparison (CERR vs controls) revealed foveal avascular zone enlargement (1.7 vs 0.23 mm, P = 0.03) and reduction of capillary vascular density (CVD) in the superficial and deep plexus in the total wide-field (43% vs 47%, P

In this case-matched study of 28 patients, early treatment with intravitreal anti-VEGF therapy preserved vision by preventing or delaying visually significant radiation maculopathy for high-risk choroidal melanoma patients following plaque radiation therapy.

Sudden and extensive growth of intraocular tumors like retinoblastoma and choroidal melanoma may result in the clinical presentation of sterile or aseptic orbital cellulitis. In such masquerading situations, ocular and orbital imaging plays a significant role. The treatment with steroids may provide a rapid recovery from the aggressive orbital inflammation. However, a high index of suspicion is vital for apt diagnosis and timely management.

Long noncoding RNAs (lncRNAs) are essential regulators of gene expression and biological behaviors. However, the contribution of lncRNA LUCAT1 to choroidal melanoma (CM) remains unexplored. Here, we examined the expression of LUCAT1 in CM cells by qRT‐PCR and investigated its biological effects by cell counting kit‐8, EdU, TUNEL, transwell assays, and Western blot. Bioinformatics tools were applied to find RNA candidates for further study. Moreover, mechanistic experiments including RNA immunoprecipitation assay, pull‐down assay, and luciferase reporter assay confirmed the relation or interaction among the indicated molecules. Here, we reported ELF1 as the transcription activator of LUCAT1. Functionally, elevated expression of LUCAT1 positively regulated CM cell proliferation, metastasis, and epithelial‐mesenchymal transition process. In addition, we verified the competing endogenous RNA (ceRNA) hypothesis of LUCAT1 and confirmed LUCAT1 modulates CM progression by modulating miR‐514a/b‐3p/RBX1 axis. Meanwhile, miR‐514a/b‐3p was suggested to repress CM progression, whereas RBX1 was unmasked to aggravate CM development. Of note, RBX1 overexpression rescued the inhibitory effect of LUCAT1 silence on the biological processes of CM cells. Altogether, this study unveiled the modulation axis ELF1/LUCAT1/miR‐514a/b‐3p/RBX1 and evidenced LUCAT1 as a promoter in CM for the first time, providing a novel insight into future treatment of CM., LUCAT1 modulates miR‐514a/b‐3p expression by serving as a sponge in CM. RBX1 is the downstream target gene of miR‐514a/b‐3p in CM.

Background To compare iodine-125 (125I) with ruthenium-106 (106Ru) episcleral plaque radiation therapy in terms of the effectiveness and non-inferiority for choroidal melanoma treatment. Objective To report the non-inferiority of new made iodine-125 (125I) compared with ruthenium-106 (106Ru) episcleral plaque radiation. Patients and methods A retrospective, non-randomized comparative case series. In this series the patients treated with 125I and 106Ru episcleral plaques for choroidal melanoma between September 2013 and August 2017 at Farabi Hospital are compared. Local control of choroidal melanomas after 125I and 106Ru plaques implantation and vision changes are the main outcome measures. Results A total of 35 patients were identified (125I = 15, 106Ru = 20). No significant difference between two groups in visual acuity, diameter and thickness changes were observed after treatment. Multivariate linear regression (MLR) analysis showed that final diameter was only, independently and significantly, correlated with the pre-treatment diameter of the tumor (β = 0.59, 95% confidence interval [CI]: 0.29, 1.34, P = 0.003). The same MLR analysis for the final thickness and visual acuity, after adjusting for age and sex showed no significant difference between two groups. A single patient treated with 106Ru had local tumor recurrence with no one in the 125I group. No statistical difference in the rate of ocular complications was observed. Conclusion The treatment with our 125I plaques is as effective as 106Ru plaques in controlling choroidal melanoma tumor and preserving the vision during the two and half year of follow-up. The complication rates are alike. It means that the effectiveness of 125I is not only comparable to 106Ru but also superior when the outcome of the interest is the thickness of the tumors.

Three cases of peripheral exudative hemorrhagic chorioretinopathy (PEHCR), which mimicked other retinal pathologies, were reported. Different preliminary diagnoses were made initially, but thorough examination combined with the appropriate investigations led to the final diagnosis of PEHCR. Despite the rare occurrence of PEHCR, it must be included in the differential diagnosis for peripheral retinal diseases.