Objective To analyse ocular and systemic findings of patients presenting with systemic metastasis. Methods and analysis It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. Results Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. Conclusions Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Background: We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed. Methods: In 24 patients with choroidal melanoma (median diameter 5.85 mm), the exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors. Results: In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death. Conclusions: Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year.

Background Episcleral brachytherapy is the most common treatment for medium-sized choroidal melanomas. Although controversial, inadequate brachytherapy dose and dose rates have at least a hypothetical implication on patient survival. Methods All patients who received ruthenium-106 or iodine-125 brachytherapy for choroidal melanoma at St. Erik Eye Hospital 1996 to 2016 were included (n=1238). Cox regression hazard ratios for melanoma-related mortality across deciles, quartiles and individual integers of apex radiation doses (Gy) and dose rates (Gy/hour) were calculated, adjusted for tumour size and location. Results The average radiation dose at the tumour apex ranged from 73.0 Gy in the first decile to 108.6 Gy in the tenth. Decreasing apex dose by 1 Gy increments or by decile or quartile group was not associated with melanoma-related mortality (p>0.2) The average radiation dose rate at the tumour apex ranged from 0.5 Gy/hour in the first decile to 2.8 Gy/hour in the tenth. Similarly, decreasing apex dose rate by 1 Gy/hour increments or by decile or quartile groups was not associated with melanoma-related mortality (p>0.5). Conclusion There are no increased hazards for choroidal melanoma-related mortality after brachytherapy with decreasing doses between 108.6 and 73.0 Gy, or with decreasing dose rates between 2.8 and 0.5 Gy/hour.

Background To reveal clinical findings related to metastatic conjunctival melanoma. Methods 10 ophthalmic oncology centres (9 countries and 4 continents) shared data to create a large clinical case series. The main outcome measures were the incidence and cumulative risk of systemic metastasis, study mortality rates and Kaplan-Meier patient mortality after developing conjunctival melanoma metastasis. Results Of 288 patients, 29 developed metastasis. Five had metastasis at presentation, were American Joint Committee on Cancer (AJCC) cT3-category and exhibited tumour-surface ulceration. Four of five (80%) had melanotic tumours with plical and/or caruncular involvement and died within 1 year. One survived 21 months. In contrast, 24 developed metastases during follow-up (mean 4.6±3.2 years). Their primary tumours were cT1 (n=13/24, 54.1%), cT2 (n=6/24, 25%), cT3 (n=2/24, 8.3%) and 3 cTx (12.5%) at presentation. Death had occurred in 17 patients (n=17/24, 71%) by the end of the study. The cumulative risk of systemic metastasis after treatment was 0.4% (95% CI 0.6% to 2.9%) at 1 year, 8.6% (95% CI 5.1% to 14.3%) at 5 years and 22.3% (95% CI 14.5% to 33.5%) at 10 years. Each increase in AJCC cT category was associated with an 89% higher risk for metastasis (HR=1.89, p<0.001). Among all 29 patients who developed metastasis, those who presented with AJCC cT3 disease were at highest risk (p<0.001). Liver and lung (n=13 each) were the most reported metastatic sites. Conclusion Metastatic conjunctival melanoma was found in 10% of conjunctival melanoma patients. Tumour-specific characteristics including AJCC cT3-category, conjunctival location and surface ulceration were associated with metastatic risk. Survival durations were shorter for those presenting with metastasis.

Background: Alzheimer’s Disease (A.D.) is a multifactorial process. Advanced glycation end products (AGEs) have been correlated with disease development¹. Additionally, high concentrations of antibodies against the food derived antigens egg‐albumin and bovine casein, have been detected in patients with Alzheimer’s disease in preliminary research presented by our team, previously (AAIC 2018).In the present study, antibodies against egg‐albumin and bovine casein as well as AGEs were detected in the cerebrospinal fluid of 36 patients with mild and 35 patients with severe Alzheimer’s Disease and 13 healthy individuals and a correlation between the measured parameters and sample properties was attempted.Method: ELISA plates pre‐treated with highly hydrophilic microlon resin were used for the purpose of this study². Egg‐albumin or bovine casein antigens were attached at the ELISA plates for the measurement of antibodies. Additionally, polyclonal antibodies against multiple AGE products were used to detect attached sample CSF AGEs.Result: According to the results, 48,6% of of the samples of patients with severe AD had anti‐egg albumin concentration higher than mean concentration of healthy idividuals+2SD (characterized as positive) compared to 8.3% of positive samples in patients with mild disease. An overall 265% increase in mean concentration was observed in severe compared to mild patients, indicating association with severity. The observed difference was significant at p = 0.01 according to mann witney U test. Lower anti‐egg albumin concentrations were observed in female samples of either mild or severe disease (Figure 1). Much lower incidence of anti‐casein antibody positive samples was found in in severe AD (5.7% positive in severe versus 0% in mild AD). A slight, not statisticaly significant, increase in mean anti‐casein antibodies concentration (23.7%) and AGEs (16.2%) was observed in severe compared to mild disease with the higher concentrations also detected in the most positive to anti‐egg albumin samples.Conclusion: The results indicated a potential correlation of antibodies against egg‐albumin with the severity of Alzheimer’s disease with increased incidence in male patients. A lower correlation was observed in case of anti‐casein antibodies and AGEs.References:1. Takeuchi et al., Current Pharmaceutical Design, 14(10), 2008, 973‐978.2. P. Eleftheriou, etal. Biomed. Res. Int., 2014.