Incidence and Risk Factors for Secondary Glaucoma in Eyes with Uveal Melanoma.

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.

BILATERAL SERPIGINOUS-LIKE CHORIORETINITIS ASSOCIATED WITH CILIOCHOROIDAL MELANOMA: A Clinicopathologic Correlation.

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.

Concurrence of peripunctal nevus and uveal melanoma with scleral pigment dispersion presenting as phthisis bulbi.

This case report demostrates an unusual occurence of peripunctal nevus and uveal melanoma, in which the clinical diganosis of uveal melanoma was masked by the atypical presentation as phthisis bulbi. Nevertheless, peculiar scleral pigment hinted at a possible intraocular tumour. The importance of meticulous clinical examination in assessment of ocular and periocular pigmented lesions is demonstrated. Further, clinicopathological differentials of correlation scleral pigmentation in diffuse necrotic uveal melanoma are illustrated.

Impact of COVID-19 pandemic on eye cancer care in United Kingdom.

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.

Clinical outcomes and secondary glaucoma after gamma-knife radiosurgery and Ruthenium-106 brachytherapy for uveal melanoma: a single institution experience.

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.

A prospective study of cancer-related benefit finding in uveal melanoma patients.

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.

Comprehensive analysis of cutaneous and uveal melanoma liver metastases.

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.

Predictors of long-term anxiety and depression in uveal melanoma survivors: A cross-lagged five-year analysis.

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.

Metastatic uveal melanoma: A valid indication for liver 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.

Molecular signatures for inflammation vary across cancer types and correlate significantly with tumor stage, sex and vital status of patients.

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.

[Excision and tectonic covering of a vascular leiomyoma of the ciliary body with large anterior staphyloma using scleral patch graft]. / Exzision und tektonische Deckung eines vaskulären Leiomyoms des Ziliarkörpers mit großem anteriorem Staphylom mittels Sklerapatch.

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.

Jejunojejunal intussusception secondary to metastatic uveal melanoma after 11 years of remission.

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.

Reflections on a Health Psychology Service for Patients with Uveal Melanoma: The Challenge of Psychological Screening and Intervention When Distress is 'Normal'.

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.

Nevus of Ota associated with a primary uveal melanoma and intracranial melanoma metastasis.

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.