The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

Characterizations of uveal melanoma patients with three additional primary malignancies.

PURPOSE: In a population-based cohort of 960 uveal melanoma (UM) patients, we describe patients with three additional malignancies, including one unique patient with four synchronous primary malignancies. METHOD: A descriptive presentation of the clinical course and outcome for UM patients with three additional primary malignancies. RESULTS: After more than 20 years of follow-up of the UM cohort, 11 patients (1.1%) were diagnosed with three additional primary malignancies before, simultaneously or after UM. Among these, one patient had four synchronous primary malignancies, detected during workup for a symptomatic UM. All diagnoses were treated during the following 4 months, firstly the breast cancer, thereafter, the lung and pancreatic cancers and finally the UM. The patient died 3 years later of abdominal carcinomatosis due to the pancreatic cancer. The family history and gene testing did not disclose any genetic predisposition for cancer. A comparison of the four synchronous tumours, morphologically and immunohistochemically, showed no similarities and the expression of antibodies was different. CONCLUSION: Patients with UM may be diagnosed with non-ocular additional primary cancers. Thus, a comprehensive workup is obligatory and a further follow-up of the UM patients seems necessary. The UM is not always the main problem.

Additional malignancies and mortality in uveal melanoma: A 20-year follow-up of a Norwegian patient cohort.

PURPOSE: The purpose of this study is to explore the frequency of additional primary malignancies in uveal melanoma (UM) patients and cause-specific mortality, to help guide surveillance strategies after UM. METHODS: All patients diagnosed with UM at Oslo University Hospital during 1990-2017 were eligible for inclusion. Linkage to the Cancer Registry of Norway obtained information on additional malignancies and cause of death throughout 2019. UM patients were categorized according to timing of additional malignancy (prior/simultaneously or after UM) or no additional cancer, and by UM stage at diagnosis. Age-adjusted mortality rates were presented per 1000 person-years with 95% confidence intervals (CI). RESULTS: The study population included 960 UM patients: 77% were diagnosed in stage and I/II and 56% were men. Mean age at diagnosis was 63 years. Additional malignancies were observed in 152 patients prior/simultaneous to UM, and in 120 patients >1 year after UM. Overall, mortality per 1000 person-years was 3.5 (95% CI 3.1-3.9) for UM and 3.0 (2.6-3.4) for other causes. Lowest UM mortality [1.3 (0.60-2.1)] was seen in patients with a second malignancy after UM, regardless of stage. Highest UM mortality was seen for UM patients in stage III/IV, both without [16.1 (13.2-19.1)] and with any additional malignancy [16.9 (6.6-27.3)]. CONCLUSION: Our results support that UM patients frequently have additional malignancies, both before and after UM. Low-UM mortality in patients with a primary malignancy after UM, might indicate less aggressive UM. The cumulative UM mortality flattens about 10 years after diagnosis and annual follow-up of patients for 10 years seems adequate.

Iris Racemose Hemangioma Assessment with Swept Source Optical Coherence Tomography Angiography: A Feasibility Study and Stand-Alone Comparison.

PURPOSE: To evaluate arteriovenous malformations (AVM) with swept-source (SS) optical coherence tomography (OCT) angiography (OCTA) in iris racemose hemangioma and compare it with traditional intravenous iris fluorescein angiography (IVFA). METHODS: A cross-sectional observational clinical study was conducted on patients with iris racemose hemangioma with the ZEISS PLEX Elite 9000 SS OCT & OCTA. RESULTS: Three eyes of three patients were imaged. Iris racemose hemangiomas demonstrated a tortuous, well-defined, and continuous course of the AVM. The ZEISS PLEX Elite 9000 SS OCT & OCTA allowed for a detailed visualization of the ARM and was superior to IVFA in depicting small caliber, fine vessels. CONCLUSIONS: SS-OCTA may provide a dye-free, no-injection, cost-effective method comparable to spectral domain OCTA and IVFA for diagnosing and monitoring iris racemose hemangiomas for growth and vascularity.

Fundus Autofluorescence Change as an Early Indicator of Treatment Effect of Brachytherapy for Choroidal Melanomas.

BACKGROUND: Early confirmation of the effect of brachytherapy for choroidal melanoma showing that tumour coverage is valuable. The irradiated retinal pigment epithelium (RPE) commonly develops atrophy. This study compares the fundus autofluorescence (AF) changes to the development of RPE atrophy following brachytherapy. METHODS: Retrospective study of 19 patients treated with 106Ru and 2 with 125I plaques with either a 3- or 6-month follow-up period. Ultra-widefield (UW) composite colour and AF images were obtained with Optomap 200Tx and interpreted as complete, partial, or no RPE changes and complete or partial hyperautofluorescence, hypoautofluorescence, or isoautofluorescence. RESULTS: At the 3-month follow-up, 9 of 13 patients (69%) (95% confidence interval [CI], 0.389-0.896) treated with 106Ru plaques developed complete homogenous hyperautofluorescence surrounding the tumour, but only 1 of 13 (8%) (95% CI, 0.004-0.379) developed complete RPE atrophy at the same time point. Six patients in the 106Ru plaque group had their first follow-up with UW imaging at 6 months. Four of them developed homogenous hyperautofluorescence and none developed complete RPE atrophy around the tumour. The 2 patients treated with 125I did not demonstrate any clear RPE or AF changes. CONCLUSION: The effect of 106Ru plaque treatment on fundus UW imaging is detected as homogenous and well-demarcated hyperautofluorescence before visible RPE atrophy.

The Small Fatal Choroidal Melanoma Study. A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To determine the size at which choroidal melanomas can metastasize and to report the characteristics of small fatal choroidal melanomas (SFCM). DESIGN: Retrospective case series. METHODS: Ten ocular oncology services submitted 45 patients with a choroidal melanoma 3 mm or less in thickness and 9 mm or less in largest basal diameter (LBD), when treated, who developed metastases. RESULTS: Median tumor thickness was 2.4 mm (range, 1.0-3.0 mm) and LBD 7.3 mm (range, 3.0-9.0 mm). Of 14 (31%) tumors that were first observed, 12 grew a median of 0.5 mm (range, 0.1-1.2 mm) in thickness and 1.0 mm (range, 0-3.0 mm) in LBD within a median of 7 months; 3 were initially smaller than 3 mm in LBD. Number of risk factors for growth and metastasis was 0 for 4% of the tumors; 60% were over 2 mm in thickness, 63% had subretinal fluid, 84% caused symptoms, 57% had orange pigment, and 92% were within 3 mm of the disc. Local recurrence occurred in 8 of 31 eyes (26%) treated conservatively. Median metastasis-free survival was 4.5 years (range, 0.8-15.7 years). Kaplan-Meier estimate of metastasis developing was 15% (95% confidence interval [CI], 7-26), 51% (95% CI, 36-64) and 85% (95% CI, 71-92) by 2, 5, and 10 years, respectively. By the time of analysis, 37 patients had died of metastasis after a median of 7 months. CONCLUSIONS: Choroidal melanomas less than 3.0 mm in LBD are highly unlikely to metastasize. Risk factors of an SFCM are similar to those for all choroidal melanomas of similar size.

The Results of Stricter Inclusion Criteria in an Immunomagnetic Detection Study of Micrometastatic Cells in Bone Marrow of Uveal Melanoma Patients - Relevance for Dormancy.

Approximately 50% of uveal melanoma patients develop metastases. We want to evaluate the effect of stricter criteria on our data from our previous study correlating survival and bone marrow (BM) micrometastasis results using our immunomagnetic separation (IMS) method. Mononuclear cell fractions (MNC) isolated from BM were examined for tumour cells and the patients were classified as BM positive (BM+) or BM negative (BM-). The study originally included 328 consecutive patients with uveal melanoma from 1997 to 2006. The cohort was limited to 217 patients when we introduced cyto- or histopathological verification of melanoma cells in the patient as a main new criterion for inclusion. Tumour cells were found in BM-samples in 38.7% (95% CI, 32-45) at enrolment. Until the latest work-up 43.8% (95% CI, 38-50) of patients had developed melanoma metastases. After a minimum follow-up time of 8.5 years, 60.4% (95% CI, 54-66) of patients had died. The causes were: melanoma metastases 69.5%, another type of cancer 5.4% and non-cancerous causes 19.5%. Overall median survival was shorter for the BM- patients (11.3 years) (95% CI, 10-12) compared to the BM+ (16.5 years) (95% CI, 12-14), p = 0.04, log rank test. All-cause mortality and specific melanoma mortality estimated after 12 year follow-up showed a highly significant difference comparing BM- and BM+, p = 0.010 and p = 0,017, respectively. IMS yields a high fraction of BM+ samples due to micrometastasis at diagnosis and these cells appear to have a positive prognostic impact strengthening our previous report. The late recurrences support the concept of tumour dormancy.

Multicellular tumor spheroids of human uveal melanoma induce genes associated with anoikis resistance, lipogenesis, and SSXs.

PURPOSE: Uveal melanoma (UM) has a high propensity for metastatic spread, and approximately 40-50% of patients die of metastatic disease. Metastases can be found at the time of diagnosis but also several years after the tumor has been removed. The survival of disseminated cancer cells is known to be linked to anchorage independence, anoikis resistance, and an adaptive cellular metabolism. The cultivation of cancer cells as multicellular tumor spheroids (MCTS) by anchorage-independent growth enriches for a more aggressive phenotype. The present study examines the differential gene expression of adherent cell cultures, non-adherent MCTS cultures, and uncultured tumor biopsies from three patients with UM. We elucidate the biochemical differences between the culture conditions to find whether the culture of UM as non-adherent MCTS could be linked to an anchorage-independent and more aggressive phenotype, thus unravelling potential targets for treatment of UM dissemination. METHODS: The various culture conditions were evaluated with microarray analysis, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), RNAscope, immunohistochemistry (IHC), and transmission electron microscopy (TEM) followed by gene expression bioinformatics. RESULTS: The MCTS cultures displayed traits associated with anoikis resistance demonstrated by ANGPTL4 upregulation, and a shift toward a lipogenic profile by upregulation of ACOT1 (lipid metabolism), FADS1 (biosynthesis of unsaturated fatty acids), SC4MOL, DHCR7, LSS (cholesterol biosynthesis), OSBPL9 (intracellular lipid receptor), and PLIN2 (lipid storage). Additionally, the present study shows marked upregulation of synovial sarcoma X breakpoint proteins (SSXs), transcriptional repressors related to the Polycomb group (PcG) proteins that modulate epigenetic silencing of genes. CONCLUSIONS: The MCTS cultures displayed traits associated with anoikis resistance, a metabolic shift toward a lipogenic profile, and upregulation of SSXs, related to the PcG proteins.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Bilateral uveal melanomas with different gene expression detected with 7 years interval.

PURPOSE: To report a bilateral uveal melanoma detected in a micrometastasis study. METHOD: Case report. RESULTS: At enucleation of a circumpapillary amelanotic mixed melanoma in a patient with ocular melanocytosis, a pigmented lesion in the other eye was detected, thought to be a naevus. BAP1 was positive showing nuclear staining of the tumour cells. Seven years later the naevus showed growth and development of a retinal detachment. FNAB disclosed monosomy 3 in the spindle tumour cells. CONCLUSION: A case of bilateral melanoma with long-term survival without metastatic diseases is reported. Different gene expressions in the two eyes were revealed. The case is a reminder that follow-up over years is essential in patients with a uveal melanoma, especially with ocular melanocytosis.

Transarterial Chemoembolization of Liver Metastases from Uveal Melanoma Using Irinotecan-Loaded Beads: Treatment Response and Complications.

PURPOSE: The purpose of this study was to evaluate treatment response and complications of transarterial chemoembolization using drug-eluting beads loaded with irinotecan (DEBIRI) in patients with liver metastases from uveal melanoma (UM). MATERIALS AND METHODS: Patients treated with DEBIRI (n = 14) were retrospectively analyzed regarding overall survival, compared to patients (n = 14) treated with intravenous dacarbazine (DTIC). Median overall survival was calculated from time of diagnosis of metastatic disease (OS1) and start of treatment (OS2). Radiological response for DEBIRI was assessed according to RECIST 1.1 on contrast-enhanced computed tomography (CT), obtained 1.5 months (range 1.2-3.7) post treatment. Major complications of DEBIRI were defined according to the Society of Interventional Radiology classification for complications by outcome. RESULTS: In the DEBIRI group, OS1 was 14.8 months (range 3.9-47.5), and OS2 was 9.4 months (range 1.7-39). Further, 11/13 (84.6%) of these patients had progressive disease on first follow-up CT and new lesions were seen in nine. There were 12 major complications in nine patients, possibly including one case of mortality due to disseminated intravascular coagulation (DIC). CONCLUSION: For patients with liver metastases from UM, the effect on overall survival of DEBIRI alone is questionable. Compared to previous reports, the response rate of DEBIRI was poor, with new liver lesions observed in the majority of patients. Major complications possibly included one case of DIC.

Autofluorescence imaging in the differential diagnosis of optic disc melanocytoma.

PURPOSE: Optic disc melanocytoma (ODM) is a benign tumour that usually occurs on or adjacent to the optic nerve head. The aim of the study was to evaluate fundus autofluorescence (FAF) imaging as a diagnostic tool in ODM. METHODS: Retrospective comparative case series study of six patients with ODM and a comparing group of four patients with juxtapapillary choroidal nevus (JCN) and four with juxtapapillary uveal melanoma (JUM). Clinical examination was supplemented with ultrasound B-scan examination and spectral-domain optical coherence tomography. FAF images were obtained with the 532-nm laser (Optomap P200Tx) from all patients. RESULTS: Clinical examination in the ODM group revealed a dome-shaped, darkly pigmented tumour on or adjacent to the optic disc in all patients, with a mean tumour basal dimension 1.4 mm and mean tumour thickness by ultrasonography of 1.0 mm. FAF revealed a totally hypofluorescent mass with sharply demarcated, feathery edges. No hyperfluorescent changes due to orange pigment or subretinal fluid were seen. In contrast, patients with JCN and JUM manifested focal hyperfluorescence as well as larger hyperfluorescent areas at the tumour and its borders. CONCLUSION: Fundus autofluorescence imaging is a non-invasive adjuvant tool in the differential diagnosis of ODM characterized by lack of hyperfluorescence compared to JCN and JUM.

Immunomagnetic detection of micrometastatic cells in bone marrow of uveal melanoma patients: a paradox.

PURPOSE: Our objective was to study survival rates with the bone marrow (BM) results in a cohort of uveal melanoma patients with long follow-up. METHODS: Mononuclear cell fractions isolated from BM were examined for tumour cells using our immunomagnetic separation (IMS) method. The patients were classified as BM positive or BM negative. Clinical follow-up, histopathological findings, vital status and cause of death were registered. RESULTS: The study included 328 consecutive patients with uveal melanoma from 1997 to 2006. Tumour cells were found in BM samples in 29% (95% CI, 25-34) at enrolment (96 cases). After a minimum follow-up time of 6 years, 156 (48%) (95% CI, 42-53) melanoma patients had died. The causes were as follows: melanoma metastases 92 (59%), another cancer 20 (13%) and non-cancer 44 (28%). Nine patients were still living with melanoma metastases. Until the latest work-up, 101(31%) (95% CI, 26-36) patients had developed melanoma metastases. Cyto- or histopathological verification of the metastatic lesions was obtained in 85 cases (84%). In the group with melanoma metastases, 28 tested BM positive at study entry (28%) (95% CI, 19-38). In total, 39 of 101 with metastases tested positive at least once after a maximum of three tests (39%) (95% CI, 29-49). The overall median survival from the first BM test was shorter for the BM negative patients (9.5 years) compared with the BM positive (14.4 years), p = 0.02, log rank test. CONCLUSION: Ocular melanoma cells detected in BM seem to have a positive prognostic impact on survival in contrast to our original hypothesis.

Malignant melanoma--diagnosis, treatment and follow-up in Norway.

BACKGROUND: The incidence of malignant melanoma in Norway is among the highest in the world and rising, with approximately 1 500 persons receiving the diagnosis annually. Correct surgical primary treatment cures 80-90%, while 10-20% experience relapses. The treatment of a metastatic malignant melanoma has changed considerably in the last 1-2 years as a result of clinical experience with new drugs. The current publication provides an updated overview of the treatment of malignant melanoma in Norway. METHOD: The article is based on a search in PubMed and on the authors' own research and clinical experience. RESULTS: After several decades with almost no change in the treatment of malignant melanoma, we have seen a positive development over the past couple of years. New treatment methods for malignant melanoma with distant spreading metastases have yielded favourable results in selected patients and are currently established in cancer departments in Norway. INTERPRETATION: Rapid and correct primary treatment is curing most patients with malignant melanoma. New drugs offer hope for selected patient groups with metastatic disease. Several new types of targeted treatment are being tested in clinical studies in Norway and elsewhere in the world.

Disseminated tumour cells in bone marrow of patients with uveal melanoma.

PURPOSE: Approximately 50% of patients with uveal melanomas develop metastases. Thus, it is important to improve our understanding of how melanoma metastases develop. METHODS: As part of a uveal melanoma micrometastasis study, we compared the detection rates of immunomagnetically selected (IMS) tumour cells in bone marrow (BM) with positively stained tumour cells using immunocytochemistry (ICC). Bone marrow mononuclear cells were isolated. Immunocytochemistry cytospin preparations were immunocytochemically stained in parallel with two different melanoma antibodies, 9.2.27 and HMB45. Using IMS, melanoma cells were selected from BM mononuclear cell fractions using immunomagnetic beads coated with the 9.2.27 antibody and identified by light microscopy. RESULTS: In cytospin preparations from 226 patients, melanoma cells were detected in 24 (10.6%), 10 with 9.2.27 and 17 with the HMB45 antibody. In three cases, we found positive cells with both antibodies. Six of the 226 (2.6%) patients that stained positively with ICC died with metastatic disease, all also positive with IMS. Sixty-six (29.2%) patients had positive BM samples with IMS at the first examination. Immunomagnetic selection (IMS) was positive in 36.8% of the 57 patients who later developed clinical metastases. Twenty-one IMS-positive patients and 31 IMS-negative patients died of metastases, in total 52 of 226 patients (23.0%). The mortality rate of melanoma metastasis was 24% (6/24) after at least 4 ½ years in ICC-positive patients compared to 38.5% (20/52) in IMS-positive patients. CONCLUSION: The presence of melanoma cells in BM of patients with uveal melanoma is documented in our study with IMS and ICC. Immunomagnetically selected is more sensitive than ICC in detecting tumour cells in BM. However, statistically, we did not find any prognostic impact of the presence of melanoma cells in BM.

Fine-needle aspiration biopsy and other biopsies in suspected intraocular malignant disease: a review.

Ocular oncologists require a strong indication for intraocular biopsy before the procedure can be performed because it carries a risk for serious eye complications and the dissemination of malignant cells. The purpose of this review is to evaluate the extent to which this restricted practice is supported by evidence from previous reports and to outline our main indications and contraindications. The different intraocular biopsy techniques in the anterior and posterior segment are discussed with a focus on our preferred method, fine-needle aspiration biopsy (FNAB). In the literature, complications are typically under-reported, which reduces the possibilities of evaluating the risks correctly and of making fair comparisons with other biopsy methods. In FNAB, the exact placement of the needle is critical, as is an accurate assessment of the size of the lesion. Fine-needle aspiration biopsy is usually not a reliable diagnostic tool in lesions < 2 mm in thickness. It is very advantageous to have a cytopathologist present in the operating theatre or close by. This ensures adequate sampling and encourages repeated biopsy attempts if necessary. This approach reduces false negative results to < 3%. Adjunct immunocytochemistry is documented to increase specificity and is essential for diagnosis and management in about 10% of cases. In some rare pathological processes the diagnosis depends ultimately on the identification of specific cell markers. An accurate diagnosis may have a decisive influence on prognosis. The cytogenetic prognostications made possible after FNAB are reliable. Biopsy by FNA has a low complication rate. The calculated risk for retinal detachment is < 4%. Intraocular haemorrhage is frequently observed, but clears spontaneously in nearly all cases. Only a single case of epibulbar seeding of malignant cells at the scleral pars plana puncture site of transvitreal FNAB has been documented. Endophthalmitis has been reported and adequate standard preoperative preparation is obligatory. An open biopsy is still an option in the anterior segment, but has been abandoned in the posterior segment. Although vitrectomy-based procedures are becoming increasingly popular, we recommend using FNAB as part of a stepwise approach. A vitrectomy-assisted biopsy should be considered in cases where FNAB fails. In any adult patient with suspected intraocular malignancy in which enucleation is not the obvious treatment, the clinician should strive for a diagnosis based on biopsy. When the lesion is too small for biopsy or the risks related to the procedure are too great, it is reasonable to be reluctant to biopsy. The standards applied in the treatment of intraocular malignant diseases should be equivalent to those in other fields of oncology. Our view is controversial and contrary to opinion that supports current standards of care for this group of patients.

Immunomagnetic detection of micrometastatic cells in bone marrow in uveal melanoma patients.

PURPOSE: Our objective was to introduce immunomagnetic separation (IMS) in ocular research by evaluating the possibility of detecting tumour cells in bone marrow (BM) and peripheral blood (PB) samples and validating the captured cells as melanocytic cells. METHODS: Mononuclear cell (MNC) fractions isolated from BM and PB in uveal melanoma patients were examined for tumour cells using our IMS method. Sheep-anti-mouse IgG antibody-coated super paramagnetic particles were conjugated to an anti-melanoma antibody. Microscopy of the magnetic fraction isolated from MNCs was performed to identify and count the number of bead-rosetted cells. The finding of at least two rosettes with coated beads in a 20-microl fraction of a sample was registered as a positive test. The melanocytic nature of the tumour cells was ascertained with a double labelling procedure using fluorescent microparticles. RESULTS: Using IMS in a study of 328 patients, tumour cells were at initial diagnosis found in BM and PB in 29.9% and 1.6% of cases, respectively. In positive samples, a median of 56 tumour cells (range 2-500) were identified. The captured cells were documented to be of melanocytic origin by the simultaneous binding of fluorescent beads coated with another melanoma-associated antibody. CONCLUSIONS: The IMS method was sensitive and efficient in the detection of occult melanoma tumour cells in BM. The validity of the immunomagnetic technique was strengthened by verifying the melanocytic characteristics of the isolated cells. The IMS procedure identifies intact, vital tumour cells, permitting further molecular characterization, an advantage which makes this method attractive for extended use. The clinical relevance of the findings will be further investigated in follow-up studies with repeated sampling and characterization of the isolated tumour cells.

Nordic research in ophthalmology.

Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.

[Retinoblastoma--hereditary eye cancer in children]. / Retinoblastom--arvelig øyekreft hos barn.

BACKGROUND: Retinoblastoma is a malignant tumour of the retina that occurs in early childhood. The aim of this paper is to give an updated review of the disease. MATERIAL AND METHODS: A review is given based on literature published over the last few years and on the authors' own experience. RESULTS: The yearly incidence of retinoblastoma is approximately one per 14 000 live births, which gives four new cases of retinoblastoma per year in Norway. The only known risk factor is heritage. Symptoms of retinoblastoma are strabismus, reduced visual acuity and red eye, but the absolutely most important sign is leukokoria (white pupillary reflex). Important diagnostic tools are ophthalmoscopy, ultrasonography, CT and MRI. The goal of treatment is to destroy all tumour tissue, but not the surrounding tissue. Treatment options are enucleation, chemotherapy, external beam radiation, radioactive isotope plaques, cryotherapy, photocoagulation, or a combination of these depending upon the size and location of the tumour. INTERPRETATION: The overall results in the treatment of retinoblastoma are favourable and have improved over the last few years because of better treatment modalities. The survival rate is approximately 95%. It is important that physicians bear in mind the signs of retinoblastoma and especially the alarming sign of leukokoria and acute strabismus in a child.