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Purpose: To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region., Methods: We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma., Results: The study included 106 eyes (age, 62.6 ± 15.2 years) with macular drusen (n = 7 globes) or parapapillary drusen (n = 29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2 ± 10.1 µm versus 34.3 ± 19.8 µm; P = 0.003), while both groups did not differ significantly in basal drusen width (74.0 ± 36.3 µm versus 108.7 ± 101.0 µm; P = 0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74 ± 0.44 µm versus 2.55 ± 0.88 µm; P = 0.57) or in RPE cell density (35.4 ± 10.4 cells/480 µm versus 32.8 ± 7.5 cells/480 µm; P = 0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60 ± 1.490 µm; P < 0.001) and RPE cell density (56.9 ± 26.8 cells/480 µm; P = 0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P > 0.10) and thickness (all P > 0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts., Conclusions: The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To estimate incidence of and analyze risk factors for developing secondary glaucoma in eyes with uveal melanoma before and after diagnosis., Design: A cross-sectional, population-based cohort study., Participants: Seven hundred eighty-one patients (median age, 64 years; range, 14-93) consecutively diagnosed with uveal melanoma from 1997 to 2012 in a national ocular oncology service, 708 (91%) of whom received ruthenium (50%) or iodine (50%) brachytherapy., Methods: Patient, tumor, treatment, and follow-up data were collected prospectively. Frequency and associations of melanoma-related glaucoma at tumor diagnosis were assessed. Incidence of developing secondary glaucoma after diagnosis was estimated by Kaplan-Meier analysis. Independent risk factors were modeled using Cox regression., Main Outcome Measures: Melanoma-related glaucoma and related risk factors., Results: Forty-five patients (5.8%; 95% confidence interval [CI], 4.2-7.6) had tumor-related secondary glaucoma at diagnosis, 34 (76%) from a narrow-to-closed angle (25 had direct angle invasion) and 10 (22%) from anterior neovascularization. Synchronous metastases were common in patients with initial secondary glaucoma (11% vs. 1.2% with incident glaucoma, P = 0.005). Patients with secondary glaucoma were often male (58% vs. 48% without glaucoma; P = 0.010) and had larger tumors (median thickness, 9.1 vs. 4.0 mm; P < 0.001) involving the ciliary body (43% vs. 21%; P < 0.001) with retinal detachment (53% vs. 30%; P < 0.001). One hundred and sixty-eight patients 165 of which were treated with brachytherapy developed incident tumor- or treatment-related secondary glaucoma a median of 1.7 years (range, 0.1-13.6) after tumor diagnosis. Cumulative proportion of developing secondary glaucoma was 23% (95% CI, 20-27) at 5 years. The most common mechanism was neovascularization in 119 patients (71%; 95% CI, 63-78). By multivariable regression, initial retinal detachment 3 to 4 quadrants (hazard ratio [HR], 2.18; P < 0.001), initial intraocular pressure 17 mmHg or higher (HR, 1.64; P = 0.01), and tumor thickness predicted incident secondary glaucoma., Conclusions: Secondary glaucoma at initial uveal melanoma diagnosis predicts high risk of synchronous metastases. Although anterior neovascularization is the most common mechanism for secondary glaucoma after diagnosis, other mechanisms such as angle narrowing and anterior chamber hemorrhage are not infrequent. Initial retinal detachment and intraocular pressure with tumor thickness could inform interim assessments of intraocular pressure and neovascularization., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the clinicopathologic correlation of a case of bilateral serpiginous-like chorioretinitis (SLC) associated with unilateral ciliochoroidal melanoma., Methods: A 71-year-old white woman was diagnosed with progressive SLC in both eyes associated with ciliochoroidal melanoma in the right eye. Clinical findings and imaging before and after enucleation in the right eye were correlated to histologic and immunohistochemistry sections., Results: Examination and imaging identified a peripheral bilobed amelanotic lesion with low reflectivity on B-scan ultrasound with an associated exudative detachment in the right eye. Additionally, multiple areas of new SLC lesions in the macula and peripapillary region in the right eye and along the inferior arcade in the left eye were observed. Oncologic evaluation confirmed a Class 2, ciliochoroidal melanoma, and the eye was enucleated. Autoimmune and infectious laboratory evaluations for the etiology of the SLC lesions were negative. Histopathology of the enucleated eye confirmed the diagnosis of uveal melanoma with lymphocytic inflammation at the edges of the tumor itself and in the areas of discrete SLC lesions. Immunohistochemistry identified similar predominantly CD3 and CD8 T cells and fewer CD20 B cells in both regions., Conclusion: Serpiginous-like chorioretinitis may present as a paraneoplastic, predominantly T-lymphocyte inflammation associated with intraocular tumor such as uveal melanoma.

The COVID-19 pandemic has had an unprecedented impact on the National Health Service in United Kingdom. The UK Ocular Oncology Services evaluated the impact on the adult eye cancer care in the UK. All four adult Ocular Oncology centres participated in a multicentre retrospective review comparing uveal melanoma referral patterns and treatments in a 4-month period during the national lockdown and first wave of the COVID-19 pandemic in 2020 with corresponding periods in previous 2 years. During the national lockdown, referral numbers and confirmed uveal melanoma cases reduced considerably, equalling to ~120 fewer diagnosed uveal melanoma cases compared to previous 2 years. Contrary to the recent trend, increased caseloads of enucleation and stereotactic radiosurgery (p > 0.05), in comparison to fewer proton beam therapy (p < 0.05), were performed. In the 4-month period following lockdown, there was a surge in clinical activities with more advanced diseases (p < 0.05) presenting to the services. As the COVID-19 pandemic continues to mount pressure and reveal its hidden impact on the eye cancer care, it is imperative for the Ocular Oncology Services to plan recovery strategies and innovative ways of working.

Little is known about contributors to the psychosocial impact of uveal melanoma, a rare cancer. Predictors and outcomes of benefit finding, a potentially favorable outcome, were investigated. Adults (n = 107) completed assessments prior to diagnosis of uveal melanoma and one week, three months and 12 months after diagnosis. Path analyses with the full information maximum likelihood estimation method were conducted. Objective disease impact on vision did not predict benefit finding (p > .05). Approach-oriented coping prior to diagnosis and one week later significantly predicted greater benefit finding 12 months later (p < .01). Avoidance-oriented coping at three months moderated the concurrent relationship of benefit finding and positive affect at 12 months (p < .001). This first study of predictors of benefit finding in uveal melanoma patients suggests that greater approach-oriented coping prospectively predicts higher benefit finding. Further, avoidance may condition the association of benefit finding with psychosocial outcomes.

We retrospectively analyzed data from records of 48 patients (48 eyes) treated with gamma-knife (n = 18) or Ruthenium-106 brachytherapy (n = 30) for uveal melanoma, in our Ocular Oncology Unit between December 2013 and September 2019, with the aim to evaluate treatment outcomes, and incidence and risk factors for secondary glaucoma. Patients demographics and tumor characteristics at diagnosis were recorded. Follow-up data were collected regarding local tumor control, treatment complications, enucleation need, metastases occurrence and survival status. The median follow-up period was 33.7 months in the gamma-knife group and 26.2 months in the brachytherapy group. The mean tumor thickness, the largest basal diameter and the tumor volume were significantly higher in the gamma-knife group than in the brachytherapy group. The local tumor control rate was 100% in the brachytherapy group and 77.8% in the gamma-knife group. In the gamma-knife group, six patients were enucleated, no patient treated with brachytherapy underwent enucleation. The overall survival rate was 96.7% in the brachytherapy group and 94.44% in the gamma-knife group. Secondary glaucoma occurred in 10 patients after gamma-knife and in one patient after brachytherapy: it should be emphasized that larger lesions were treated with gamma-knife, whereas smaller tumors were selected for brachytherapy. We found a significative correlation of tumor thickness (P value = 0.043) and volume (P value = 0.040) with secondary glaucoma occurrence after gamma-knife treatment. Moreover, secondary glaucoma significantly correlated with radiation retinopathy in the gamma-knife group (P value = 0.009). This study shows preliminary clinical results that could be useful for further studies with more patients and longer follow-up., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB., Methods: Tumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level., Results: Comparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases., Conclusions: While TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered., Competing Interests: Competing interests: EAR received travel support from NanoString Technologies and MSD. TMV received travel support from BMS. JWR is an employee and stockholder of Nanostring Technologies. SW is an employee and stockholder of Nanostring Technologies. PK reports receiving commercial research grants from Bristol-Myers Squibb and Merck and is a consultant/advisory board member for Neon Therapeutics and Personalis. RAS reports having received fees for professional services from Qbiotics, Novartis, MSD Sharp & Dohme, NeraCare, AMGEN, Bristol-Myers Squibb, Myriad Genetics, GlaxoSmithKline and us supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant and NHMRC Practitioner Fellowship. Support from the Ainsworth Foundation, ClearBRIDGE Foundation and colleagues at Melanoma Institute Australia and Royal Prince Alfred Hospital are also gratefully acknowledged. EK has served as a consultant advisor for BMS, Novartis, Roche, Merck, Amgen, Pierre-Fabre, EISAI, Bayer, Genzyme-Sanofi for which the institution (LUMC) received funding, and received research grants from BMS. DSP is cofounder, shareholder and advisor of Immagene B.V. GVL is consultant advisor for Aduro, Amgen, Bristol-Myers Squibb, Highlight Therapeutics S.L., Mass-Array, Merck, MSD, Novartis, OncoSec Medical, Pierre Fabre, Roche, QBiotics, Skyline DX and Sandoz. TS has served as a consultant advisor for Adaptive Biotechnologies, AIMM Therapeutics, Allogene Therapeutics, Amgen, Merus, Neon Therapeutics, and Scenic Biotech; is recipient of grant and research support from MSD, BMS, and Merck KGaA; is a stockholder in AIMM Therapeutics, Allogene Therapeutics, Merus, Neogene Therapeutics, and Neon Therapeutics; and is a venture partner at Third Rock Ventures. CB reports personal fees as a consultant advisor for BMS, MSD, Novartis, Lilly, Pfizer, GSK, GenMab, Pierre Fabre and Third Rock Venture for which the institute (Netherlands Cancer Institute) received payments, has received research grants from BMS, Novartis, and NanoString Technologies all paid to the institute (Netherlands Cancer Institute), and is cofounder of Immagene B.V., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cancer survivors commonly experience long-term anxiety and depression. Anxiety and depression might result from problems emerging during survivorship rather than illness and treatment. This study tested three potential causal paths: (a) concerns about physical symptoms and functional problems and fear of cancer recurrence (FCR) arising during survivorship directly cause anxiety and depression, (b) an indirect path whereby FCR mediates effects of concerns about physical symptoms and functional problems on anxiety and depression, and (c) a reciprocal path whereby anxiety and depression cause concerns about physical symptoms and functional problems and FCR, which exacerbate later anxiety and depression., Methods: Sample of 453 uveal melanoma survivors who completed observations 6-, 12-, 24-, 36-, 48- and 60-months post-diagnosis and did not miss two consecutive observations. Cross-lagged analyses were conducted to predict Hospital Anxiety and Depression Scale subscale scores. Symptoms and functional problems were measured using the EORTC OPT 30 scale, and FCR operationalised by the EORTC OPT 30 worry about recurrence scale. Covariates were age, gender, treatment modality, and visual acuity of the fellow eye and chromosome-3 status (which accurately predicts 10-year survival), worry and anxiety or depression., Results: All paths received some support, although the indirect path emerged only for anxiety in females. Concerns about physical symptoms, functional problems, and FCR originated in survivorship and appeared to both influence and be influenced by anxiety and depression., Conclusions: Findings emphasise the importance of actively monitoring survivors to prevent, detect, and intervene in the development of anxiety and depression during survivorship., (© 2020 John Wiley & Sons Ltd.)

Cancer affects millions of individuals worldwide. One shortcoming of traditional cancer classification systems is that, even for tumors affecting a single organ, there is significant molecular heterogeneity. Precise molecular classification of tumors could be beneficial in personalizing patients' therapy and predicting prognosis. To this end, here we propose to use molecular signatures to further refine cancer classification. Molecular signatures are collections of genes characterizing particular cell types, tissues or disease. Signatures can be used to interpret expression profiles from heterogeneous samples. Large collections of gene signatures have previously been cataloged in the MSigDB database. We have developed a web-based Signature Visualization Tool (SaVanT) to display signature scores in user-generated expression data. Here we have undertaken a systematic analysis of correlations between inflammatory signatures and cancer samples, to test whether inflammation can differentiate cancer types. Inflammatory response signatures were obtained from MsigDB and SaVanT and a signature score was computed for samples associated with 7 different cancer types. We first identified types of cancers that had high inflammation levels as measured by these signatures. The correlation between signature scores and metadata of these patients (sex, age at initial cancer diagnosis, cancer stage, and vital status) was then computed. We sought to evaluate correlations between inflammation with other clinical parameters and identified four cancer types that had statistically significant association (p-value < 0.05) with at least one clinical characteristic: pancreas adenocarcinoma (PAAD), cholangiocarcinoma (CHOL), kidney chromophobe (KICH), and uveal melanoma (UVM). These results may allow future studies to use these approaches to further refine cancer subtyping and ultimately treatment., Competing Interests: We have the following interests: David Lopez is employed by Gilead Pharmaceuticals. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Benign tumors of the ciliary body are rare and may potentially be confused with uveal melanoma in clinical routine. Clinical findings rarely allow for safe differentiation. Hence primary excisions are frequent. We report the case of a patient with a benign ciliary tumor, which was observed over a total of 13 years and eventually underwent a local tumor resection.

Purpose: Owing to its relative resistance to chemotherapeutics, prognosis following the diagnosis of metastatic uveal melanoma has remained disappointing. On this basis, liver resection in cases of isolated hepatic metastases has been postulated as a viable treatment option. Herein we performed an analysis of patients who underwent hepatic metastatectomy for uveal melanoma and compared their outcomes to those undergoing resection for colorectal cancer liver metastases (CRLM) in the same time period., Methods: From 2008 to 2018, all patients referred to our unit with hepatic metastases were included for analysis. Performing a 3:1 matched cohort analysis, patients with metastatic uveal melanoma were matched for age, sex, operative approach, tumour number and size to those undergoing resection for CRLM. Clinicopathological data was sought from a prospectively maintained database and reviewed along with 30-day post-operative morbidity and mortality., Results: Fifteen patients underwent hepatic metastasectomy for primary uveal melanoma. A further 45 patients undergoing hepatectomy for metastatic colorectal cancer acted as the control group. No in-hospital mortality was noted with four patients (26.6%) developing post-operative morbidity. The median follow-up period following melanoma resection was 27 months (range 5-211) with 1-, 3- and 5- year overall survival for this cohort of 86.6%, 53.3% and 40%, respectively. There was no difference in overall survival between the melanoma and CRLM group (p =0.80)., Conclusion: In patients presenting with hepatic metastases from uveal melanoma, this present study supports the rationale to proceed to surgery with acceptable morbidity and mortality.

We appraise the role of screening for distress as part of health psychology assessment of patients newly diagnosed with cancer. We reviewed records of consecutive patients who accepted a health psychologist's assessment over 4 years, examining convergence and divergence of the result of screening (whether patients reached threshold as 'cases') with the psychologist's clinical judgment of need for intervention. Of 261 patients, 88 (33.7%) were 'cases'. Of these, need for psychological intervention was identified in 70 (79.5%). Of the 173 (66.3%) 'non-cases', need was identified in 59 (34.1%). Examination of cases where the psychologist's judgment diverged from screening showed that 'caseness' can arise from distress that patients can manage themselves and, conversely, that psychological needs arise in the absence of overt distress. Formal screening may not identify need for psychological intervention. The psychologist's role is to make expert judgments of patients' current and future needs. Dialogue with patients should be the vehicle for assessment.

Malignant cutaneous melanoma frequently metastasises to gastrointestinal tract, small bowel being the most common site likely due to its rich vascular supply. However, most common sites for metastatic uveal melanoma are the liver (93%), lung (24%), bone (16%), skin/subcutaneous tissue (11%) and lymph nodes (10%). 1 We present a case of 46-year-old man with jejunojejunal intussusception secondary to metastatic uveal melanoma status postbrachytherapy after 11 years of remission. We aim to highlight the rare occurrence of adult intussusception secondary to uveal melanoma after a prolonged period of remission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Headaches and visual complaints are common conditions encountered in the emergency department. While a patient's age, risk factors, and comorbidities often aid in risk stratification and guide emergency department evaluation, atypical presentations of serious disease may still occur in young otherwise healthy patients CASE: In this vignette we discuss a case of ocular (choroidal) melanoma in a 21 year-old female patient who presented with recurrent photopsia and headaches., Discussion: Ocular melanoma is the most common non-skin melanoma and should be considered by the emergency physician for patients with visual deficits. Likely presentations and risk factors for ocular melanoma will be discussed as well as emergency department and specialty management., (Copyright © 2018. Published by Elsevier Inc.)

Nevus of Ota is a blue, hyperpigmented, benign dermatosis of the skin and mucosae that most often occurs unilaterally in the distribution of the ophthalmic (V1) and maxillary (V2) branches of the trigeminal nerve. Although uncommon, association with malignant melanoma is a complication that must be considered in the evaluation of patients with nevus of Ota. Mutations in the GNAQ and BAP1 genes in patients with nevus of Ota place them at higher risk for malignant melanoma and metastasis. We report the case of a 29-year-old woman with a long-standing history of nevus of Ota who presented acutely with an intracranial melanoma as an extension of a primary uveal melanoma.

Competing Interests: There are no conflicts of interest

Purpose: To provide a clinical description of the long-term outcome of a 103 Pd plaque-irradiated ciliary body melanoma with extrascleral extension while attempting to preserve a subadjacent glaucoma filtering bleb., Methods: A 75-year-old woman with pseudoexfoliative glaucoma for 17 years, 16 years status post argon laser trabeculoplasty, and 15 years status post trabeculectomy in the left eye, was diagnosed with an ipsilateral ciliary body melanoma with visible extrascleral extension. Treatment involved insertion of a 103 Pd radioactive plaque over the functioning trabeculectomy, with removal 7 days later. At plaque insertion, amniotic membrane grafts were used to cover the plaque and protect the filtering site., Results: The tumor was successfully treated without clinical evidence of harm to the filtering bleb, with resultant stable intraocular pressure. However, the patient developed blebitis 1.5 years later. Though it resolved with topical antibiotic therapy, the bleb became less succulent. Two years postoperatively, she developed a spontaneous hyphema that resolved after one injection of transscleral bevacizumab 1.25 mg. Her tumor continually regressed in thickness. Without additional glaucoma surgery, her intraocular pressure remained well-controlled on topical medications for 6 years., Conclusions: Ciliary body melanoma with minimal extrascleral extension beneath a functioning filtering bleb can be treated using radioactive plaque therapy. In this case, we were able to achieve both tumor regression and glaucoma control by covering the plaque with an amniotic membrane graft.

Background: To report on radiation-related side effects and complications after ruthenium-106 plaque brachytherapy of uveal melanomas., Methods: Medical records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy between 1997 and 2012 at a single center, were analyzed. We evaluated the occurrence of radiation-related side effects on the anterior and posterior segment of the eye. The influence of patient, tumor and treatment parameters on outcome was analyzed by multivariate time to event analysis considering competing risks., Results: The median overall follow-up was 37.9 months. After treatment, the estimated risk at 12, 24 and 48 months for developing anterior segment complications was 25.3%, 37.5% and 50.3% for cataract formation and 5.4%, 6.4% and 8.1% for secondary glaucoma, respectively. The estimated risk for the occurrence of posterior segment complications 12, 24 and 48 months after treatment was 3.1%, 6.7% and 18.3% for radiation retinopathy, 18.3%, 27.1% and 42.6% for radiation maculopathy and 16.5%, 21.0% and 32.8% for radiation neuropathy, respectively. The risk of an increase in retinal detachment after treatment was 14.7%, 14.7% and 17.4% at 12, 24 and 48 months, respectively. The risk of vitreous hemorrhage occurring after treatment was 6.2%, 8.1% and 12.7%, and the risk of tumor vasculopathy was 15.4%, 17.4% and 19.0%. Scleral necrosis was observed in one patient., Conclusion: Radiation-related side effects and complications are common among patients treated with ruthenium brachytherapy for uveal melanoma. However, the risk for those largely depends on individual tumor parameters. Before treatment, patients should be informed of their specific risks to develop various side effects. Patient information before treatment should cover not only general information about the treatment and possible complications and side effects but should also give details on the specific risks of the patient in her individual situation. This also includes elucidating the patient's individual resources and expectations and her willingness for long-term regular follow-up examinations and secondary adjunct treatments.

Uveal melanoma patients have a poor survival after the diagnosis of metastatic disease. Isolated hepatic perfusion (IHP) was developed to treat patients with unresectable metastases confined to the liver. This retrospective analysis focuses on treatment characteristics, complications, toxicity and survival after IHP. Patients with uveal melanoma metastases confined to the liver treated with IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC Cancer Institute and Leiden University Medical Center) were included. Between March 1999 and April 2009, 30 patients were treated with IHP. The duration of surgery was 3.7 h (Erasmus MC Cancer Institute) versus 8.7 h (Leiden University Medical Center) and also the dosage of melphalan differed: 1 mg/kg body weight (n=12) versus a dose of 170-200 mg (n=18) or melphalan (100 mg) combined with oxaliplatin (50 or 100 mg) (n=3). The length of hospital stay was 10 days. Two patients developed occlusion of the hepatic artery and died, respectively, 3 days and 1.5 months after surgery. Progression-free survival was 6 (1-16) months and recurrences occurred mainly in the liver. The median overall survival was 10 (3-50) months. IHP is a potentially beneficial treatment modality resulting in a reasonable overall survival for uveal melanoma patients. Because of considerable morbidity related to the open procedure, a percutaneous system has been developed and is currently being investigated.

Purpose: To describe a case of iris melanoma for which a patient refused treatment for 15 years, and the complications that resulted., Methods: Single case report., Results: A 52-year-old white man was evaluated for a suspicious pigmented lesion of the left iris. He was followed closely with serial examinations and ultrasound biomicroscopy, and he refused therapy when the lesion showed growth 15 years after presentation. The patient subsequently developed recurrent hyphema, intraocular pressure up to 55 mmHg, and glaucomatous optic neuropathy. He eventually underwent iodine-125 brachytherapy resulting in tumor regression and improvement of intraocular pressure., Conclusion: Untreated iris melanoma can develop complications such as recurrent hyphema and glaucoma with irreversible optic nerve damage. Treatment of slow-growing iris melanoma must be considered to prevent complications.

Metastatic bladder tumors constitute <5% of all bladder tumors and metastatic malignant melanoma of the urinary bladder is very rare. We present a case report of a metastatic malignant melanoma of the urinary bladder. A 70-year-old woman without any apparent significant clinical history was admitted to the Department of Urology for gross hematuria. Microscopic findings of the transurethral resection specimen revealed fascicles, sheets, and diffuse areas composed of oval and fusiform cells with focal pigmentation. Immunohistochemical analysis revealed that the tumor cells were positive for human melanoma black-45, Melan-A, and S100, and negative for pancytokeratin. Subsequently, we contacted the patient and learned that she was admitted to the Department of Ophthalmology for painless and progressive visual field loss 15 years ago. She had been diagnosed with a primary ocular (uveal) melanoma. A detailed patient history coupled with histological and immunohistochemical findings were necessary to make the final diagnosis of metastatic melanoma.

Uveal melanoma is a rare subtype of melanoma, accounting for only 3-5% of all melanoma cases in the USA. Although fewer than 4% of uveal melanoma patients present with metastasis at diagnosis, approximately half will develop metastasis, more than 90% of which disseminate to the liver. Infrequently, a number of malignancies can lead to leptomeningeal metastases, a devastating and terminal complication. In this case report, we present an exceedingly rare case of a patient with uveal melanoma who developed leptomeningeal carcinomatosis as the sole site of metastasis. After conventional methods to diagnose leptomeningeal carcinomatosis fell short, a diagnosis was confirmed on the basis of identification and genomic analysis of melanoma circulating tumor cells in the cerebrospinal fluid.

Purpose: To measure scleral and choroidal volume in eyes of Chinese, and to assess associations with age and axial length., Methods: We histomorphometrically examined globes from infants and adults which had been enucleated due to retinoblastoma, uveal melanoma, or absolute painful glaucoma. Thickness of sclera and choroid were measured, and volumes were calculated., Results: The study included 225 globes (mean axial length: 24.6 ± 4.2 mm; range:17.0-35.7 mm; mean age: 30.4 ± 22.6 years; range: 1-83 years). Mean computed scleral volume was 648 ± 136 mm(3). Scleral volume in children aged <5 years significantly increased with longer axial length (P = 0.001; correlation coefficient r: 0.42) and older age (P = 0.003; r: 0.39) in univariate analysis. In multivariate analysis within the group of children aged ≤2 years, larger scleral volume increased with longer axial length (P = 0.04; standardized correlation coefficient beta: 0.32; correlation coefficient B: 21.6; 95 % confidence interval (CI): 0.52, 42.7) and showed a statistically non-significant tendency to increase with older age (P = 0.06;b eta: 0.30; B: 56.9; 95% CI: -1.5,115). In individuals aged ≥ 5 years, scleral volume was not significantly associated with axial length (P = 0.75) or age (P = 0.13). Mean choroidal volume as measured and calculated in 95 individuals (age: 16-81 years) was 44.1 ± 14.1 mm(3), and was not significantly associated with age (P = 0.47; r: -0.08) or axial length (P = 0.83; r: -0.02)., Conclusions: This study on children eyes with retinoblastoma and adult eyes with malignant melanomas or end-stage glaucoma suggests that primary eye growth up to an age of 2 years is associated with an increase in scleral volume. After the age of 2 years, scleral volume and choroidal volume remain unchanged, leading to scleral and choroidal thinning with longer axial length, in particular at the posterior pole.

Purpose: To assess differences in scleral and choroidal thickness between eyes with secondary high axial myopia caused by congenital glaucoma, eyes with primary high axial myopia, and nonhighly myopic eyes., Methods: The study consisted of 301 Chinese individuals with a mean age of 23.9 ± 22.6 years and mean axial length of 24.8 ± 4.2 mm. It included the "secondary highly myopic group" (SHMG) because of congenital glaucoma (n = 20 eyes; axial length >26.0 mm), the "primary highly myopic group" (PHMG) (n = 73; axial length >26.0 mm), and the remaining nonhighly myopic group (NHMG)., Results: The secondary highly myopic group versus the primary highly myopic group had significantly thinner sclera in the pars plana region (343 ± 71 μm versus 398 ± 83 μm; P = 0.006), whereas scleral thickness in other regions did not differ significantly between both highly myopic groups and was significantly thinner in both highly myopic groups than in the NHMG. Mean total scleral volume did not differ significantly (P > 0.20) between any group (SHMG: 659 ± 106 μm; PHMG: 667 ± 128 μm; NHMG: 626 ± 135 μm). Choroidal thickness was significantly thinner in both highly myopic groups than in the NHMG, with no significant differences between both highly myopic groups. Choroidal volume did not differ significantly (P > 0.40) between any of the groups (SHMG: 43 ± 12 μm; PHMG: 43 ± 13 μm; NHMG: 46 ± 17 μm)., Conclusion: In secondary high axial myopia, the sclera gets thinner anterior and posterior to the equator; whereas in primary high axial myopia, scleral thinning is predominantly found posterior to the equator. Because volume of sclera and choroid did not differ between any group, scleral and choroidal thinning in myopia may be due to a rearrangement of tissue and not due to the new formation of tissue.

Background: Retrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma., Methods: In this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010., Results: The median IOP decreased significantly from 35 mmHg ± 8.8 before TE to 16 mmHg ± 8.2 (=52.3 %) six months after TE (Wilcoxon-Mann-Whitney-U Test, p<0.01). None of the patients needed any glaucoma medication six months after trabeculectomy. Two patients developed local recurrence during follow-up, which were independent of the trabeculectomy. One patient had to be enucleated due to intractable pain and suspected remaining tumor activity. One patient died due to metastasis., Conclusions: Trabeculectomy is an option in intractable glaucoma in patients with uveal melanoma after proton beam therapy in single cases. Secondary interventions are common. Inoculation metastases are possible. Secure local tumor control must be a prerequisite for filtrating operations.

Purpose: To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort., Methods: Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52)., Results: Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated., Conclusion: UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness.

A 20-year-old woman with congenital iris heterochromia presented with loss of vision of her right eye. We made de diagnosis of a large 'uvea melanoma' and enucleated the eye. Pathological examination showed an underlying oculodermal melanocytosis (ODM). The life-time risk of uveal melanoma in the general population is 0.7:100,000, but 1:400 in patients with ODM. Therefore, annual fundoscopy is recommended in these patients.

Case Report: We present a case of plateau iris and glaucoma due to multiple unilateral iridociliary cysts. The patient was treated with iridotomy Nd: YAG laser and 360° iridoplasty, without achieving pressure control. Phacoemulsification improved the hypertension. Dynamic gonioscopy and OCT of the anterior chamber was also performed before and after treatment., Discussion: Iridociliary cysts are a benign condition that can cause iris plateau configuration, and can produce a difficult to treat ocular hypertension. Cystotomy, peripheral iridoplasty, and other treatments have been proposed., (Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To describe aqueocentesis cytopathology results from dogs and cats presenting for uveitis investigation and to determine whether this is a useful and safe procedure., Animal Studied: Dogs and cats presenting for investigation of anterior uveitis (April 2008-December 2013)., Procedures: Aqueous was collected via limbal entry under sedation/general anesthesia, for cytopathology and occasionally bacterial culture or polymerase chain reaction (PCR) testing. Further workup included blood testing (hematology, biochemistry, and serology), diagnostic imaging, nonocular cytopathology, and available histopathology., Results: Fifty-six dogs and 39 cats were included in the study. An aqueous cytopathologic diagnosis of lymphoma (or discrete cell neoplasia) was made in six dogs and seven cats, and a diagnosis of large cell carcinoma made in one dog. This diagnosis of lymphoma was confirmed by ocular histopathology in two dogs and one cat; nonocular cytopathology corroborated lymphoma in another three dogs and five cats. Lymphoma was not evident on aqueous cytopathology but confirmed on nonocular histopathology in two dogs and by cytopathology in one cat. Additionally, aqueous cytopathology in three cats suggested, but was not considered diagnostic of, lymphoma; one of these cats had a confirmatory diagnosis of lymphoma on subsequent clinical investigation. Aqueous humor cytopathology alone was not diagnostic in non-neoplastic anterior uveitis cases, but supplemented the clinical picture with other systemic diagnostic tests. No clinically important complications were reported in association with aqueocentesis., Conclusions: Aqueocentesis is performed readily with minimal risk. The results were primarily useful in aiding a diagnosis of lymphoma in both dogs and cats., (© 2014 American College of Veterinary Ophthalmologists.)

Melanomas account for over 70% of adult malignancies in the eye and occur primarily in the choroid. Melanomas rarely originate in the ciliary body, with an annual incidence of approximately 1.6 cases per million. While the incidence rate of these tumors is low, malignant melanomas metastasize at early stages of disease development and show poor prognoses. Malignant melanomas of the ciliary body are often deeply hidden and have complex clinical manifestations, which are easily misdiagnosed and affect the prognosis. Here, we report a case of monocular ciliary body melanoma in an elderly Asian woman. Using this case as an example, we perform a systematic review of the disease's clinical symptoms, signs, diagnoses, differential diagnoses, treatment and prognosis.

We report the case of a man affected by a unilateral Ménière's disease who, after being free from vertigo spells and tinnitus for more than ten years, manifested an exacerbation of symptoms just before the diagnosis of a choroidal melanoma. Melanoma is an aggressive form of cancer derived from neuroectodermal melanocytes. Melanocytes are present in the inner ear where they contribute to the production of endolymphatic potentials and to the maintenance of normal volumes of the inner ear fluids. A possible autoimmune connection between the exacerbation of audiovestibular symptoms and melanoma is discussed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Importance: Schnabel cavernous degeneration (SCD) has been observed in eyes with uveal melanoma (UM), but, to our knowledge, a definitive study establishing the association between SCD and UM has not been conducted., Objective: To explore an association between SCD and UM., Design, Setting, and Participants: A historical cohort analysis was performed using histologic slides and related clinical records of cases from the Collaborative Ocular Melanoma Study and Eye Pathology Laboratory at the University of Wisconsin, including 1985 UM eyes, 517 eye bank eyes, and 155 enucleated glaucomatous eyes., Main Outcomes and Measures: The prevalence of SCD was calculated and compared between each group; subgroup analysis was also conducted of eyes with and without SCD for the prevalence of glaucoma., Results: Schnabel cavernous degeneration was seen in 17 (0.9%) UM eyes, 9 (1.7%) eye bank eyes, and 2 (1.3%) enucleated glaucomatous eyes. No difference was detected between the prevalence of SCD in UM eyes and eye bank eyes (odds ratio [OR], 0.49; 95% CI, 0.22-1.10) or enucleated glaucomatous eyes (OR, 0.66; 95% CI, 0.15-2.89). Subgroup analysis, performed on 421 UM eyes, provided sufficient clinical information to definitively establish the presence or absence of glaucoma. Of the 95 (22.6%) eyes with glaucoma, 11 (11.6%) revealed histopathologic evidence of SCD. Compared with enucleated end-stage glaucoma eyes, this represents a 10-fold increase in SCD in UM eyes with glaucoma (OR, 10.10; 95% CI, 2.17-46.26). The prevalence of glaucoma in UM eyes with SCD, however, was respectively 7- and 15-fold higher than the prevalence of glaucoma in SCD-negative UM eyes (OR, 6.98; 95% CI, 2.51-19.43) and SCD-positive eye bank eyes (OR, 14.67; 95% CI, 1.46-146.97)., Conclusions and Relevance: Although an association between SCD and UM was not confirmed, subgroup analysis did reveal an increased incidence of SCD in eyes with both UM and glaucoma. This suggests that the occurrence of glaucoma may increase the risk of SCD in eyes with UM.

Purpose: To evaluate retrospectively the usefulness of the red diode and krypton laser for transscleral contact cyclophotocoagulation (CPC) in the treatment of secondary glaucoma in eyes with uveal melanoma., Patients and Methods: Twenty-seven eyes of 27 patients (mean age, 66 y; range, 33 to 85 y) with a uveal melanoma and secondary glaucoma were treated with a transscleral 670-nm diode (40 treatments) and 647-nm krypton (5 treatments) laser CPC; 25 eyes had been or were subsequently treated with brachytherapy. The energy used was 420 mW at the tip of the probe (exposure time, 10 s). Seventeen eyes were treated once, 6 eyes twice, and 4 eyes 3 to 6 times. The aim was to preserve vision in 21 patients and to relieve pain in 6 patients. Fourteen patients (52%) died during follow-up., Results: With ≥1 CPCs, the intraocular pressure decreased from a median of 40 mm Hg at baseline to 28 mm Hg at 12 months (n=18) and 23 mm Hg at 24 months (n=10). Hypotony developed in 6 eyes. Before CPC, 12 eyes had a best corrected visual acuity (BCVA) of 20/400 or better. At 12 months, 5 of 18 eyes had BCVA 20/400 or better, and at 24 months 4 of 10 eyes. Four eyes were removed. At the latest visit, 15 of 23 eyes had no light perception, but were preserved. All patients whose aim of treatment was to relieve pain achieved pain relief., Conclusions: CPC lowered intraocular pressure and the number of medications needed for secondary glaucoma in eyes with uveal melanoma, also providing pain relief.

Paraneoplastic cerebellar degeneration (PCD) is characterized by subacute development of pancerebellar dysfunction as a remote effect of a systemic cancer and usually develops in patients affected by gynecological tumors. Uveal melanoma is a very rare disease with a severe prognosis. A 58-year-old man affected by uveal melanoma developed anti-Yo positive paraneoplastic cerebellar degeneration (PCD) 42 months after the initial diagnosis. The onset and worsening of the neurological symptoms were parallel to the course of liver metastasis. To our knowledge this is the first case of PCD in a patient with uveal melanoma. We speculate that the cerebellar degeneration-related protein 2 (CDR2), to which the anti-Yo antibodies are directed, may have been expressed in melanoma cells and conferred proliferative advantage to the disease., (© 2013.)

The incidence of uveal melanoma, in particular that of the ciliary body, is very low in black people, including West Indians. When symptomatic, it manifests as decreased or impaired visual acuity and seldom, if ever, pain. We report a case of ciliary body melanoma that is of scientific interest for two reasons: 1) a West Indian melanoderm patient being affected, 2) presentation as a recurrent uveitis with a transient increase of intraocular pressure, and without any decline in visual acuity. We recommend that in any case of uveitis, black patients included, a ciliary body tumor should always be excluded by pupillary dilation., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Cases Report: We report the cases of 2 women with a pigmented tumour in the ciliary body, one a melanocytoma and the other a melanoma, with different clinical manifestations. The first one presented with decreased visual acuity associated with recent growth of the tumour, as well as sectorial opacities of the lens and subluxation. The second one is asymptomatic and has been kept under observation for more than 30 years., Discussion: Although the definitive diagnosis of a pigmented tumour of the ciliary body is only achieved by the histopathology study, the group of clinical features is a determining factor when a conservative treatment is indicated., (Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.)

Clinical Case: No intraocular biopsy technique is free of risk and all have the possibility of giving false negatives due to the difficulty in obtaining a sufficient sample. A modified chorioretinal biopsy was performed on a patient with suspected choroidal melanoma after negative biopsy with 25G vitrectomy. In addition to removing a solid fragment of tumor material using bimanual surgery, material from the lesion was obtained with the vitreotome to perform cytology, which confirmed the diagnosis of melanoma., Discussion: Cytology obtained through the vitreotome in association with removing a solid sample of the choroidal lesion may improve the efficiency of intraocular biopsy., (Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.)