[Impact of COVID-19 on a rare disease (uveal melanoma) in a national reference unit of intraocular tumors in Spain]. / Impacto del COVID-19 en una enfermedad rara (melanoma uveal) en una unidad de referencia nacional de tumores intraoculares en España.

Objective: To analyze the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumor included in the Orphanet catalog of rare diseases) in a Spanish national reference unit for intraocular tumors during the first year of the pandemic. Material and methods: An observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analyzing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumor size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. Results: Eighty-two patients with uveal melanoma were included, of which 42(51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumor size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p < 0.05). Multivariable logistic regression demonstrated that both medium-large tumor size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p < 0.01 and OR 10; 95% CI,1.10-90.25; p = 0.04, respectively). Conclusions: The increase in tumor size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

Impact of COVID-19 on a rare disease (uveal melanoma) in a national reference unit of intraocular tumors in Spain.

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumour included in the Orphanet catalogue of rare diseases) in a Spanish national reference unit for intraocular tumours during the first year of the pandemic. METHOD: An observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analysing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumour size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. RESULTS: Eighty-two patients with uveal melanoma were included, of which 42 (51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumour size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p < 0.05). Multivariable logistic regression demonstrated that both medium-large tumour size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p < 0.01 and OR 10; 95%CI, 1.10-90.25; p = 0.04, respectively). CONCLUSIONS: The increase in tumour size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

Ocular oncology service during the COVID-19 outbreak: uveal melanoma characteristics presenting in 2019 compared to 2020.

AIM: We aim to evaluate the impact of the COVID-19 pandemic on ocular oncology in Ireland, comparing uveal melanoma trends in 2019 to 2020. METHODS: Patients included for analysis were those that presented to the ocular oncology service from January 2019 to December 2020 in the Royal Victoria Eye and Ear Hospital in Dublin, who underwent primary treatment for uveal melanoma-proton beam therapy, brachytherapy or enucleation. RESULTS: Ninety-seven patients presented in 2019 (n = 46) and 2020 (n = 51) who underwent primary treatment for uveal melanoma. Presentation via the eye casualty department was more common in 2020. Dimensions of choroidal melanomas were increased both in basal diameter and thickness compared to those in 2019. More patients had enucleations in 2020 than in 2019 (21.6% vs 9.3%, respectively) and less had proton beam therapy (6.2% vs 12.4%). More patients had evidence of extra-scleral extension at the time of surgery in 2020 compared to 2019 (4.1%, n = 4 versus 0%, respectively). The mean duration of brachytherapy therapy was longer in 2020 (5.3 days ± 35.8) compared to 2019 (4.6 days ± 38.7). Mean time between presentation and primary treatment was 35.6 ± 28.8 days in 2019 and 24.1 ± 20.4 days in 2020. CONCLUSIONS: More advanced disease is suggested by the increased mean basal diameter and tumour thickness, extra-scleral extension and longer duration of brachytherapy. Time from diagnosis to treatment was not delayed in 2020.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

Comparison of Tumor Size and Gene Expression at Presentation in Uveal Melanoma Patients before and during the COVID-19 Pandemic.

Introduction: The aim of this study was to compare the clinical and gene expression variables of uveal melanoma patients presenting before and after the start of the COVID-19 pandemic as surrogate markers in order to assess the pandemic's potential impact on care. Methods: We conducted a retrospective chart review of uveal melanoma patients at Retina Consultants of Texas and assessed tumor size, staging, and gene expression data during two time periods: May 2019 to February 2020 (Group 1: Before the COVID-19 pandemic declaration by the WHO in March 2020) and May 2020 to March 2021 (Group 2: After the start of the COVID-19 pandemic). Results: A total of 80 patients with uveal melanoma were studied (Group 1: 40 [50%] and Group 2: 40 [50%]). There was no statistically significant difference in the tumor thickness (p = 0.768), largest base dimension (p = 0.758), Collaborative Ocular Melanoma Study size class (p = 0.762), and American Joint Committee on Cancer stages (p = 0.872) between the two groups. Additionally, there was no difference in the tumors' gene expression data including gene expression profile class (p = 0.587) and PRAME expressivity (p = 0.861) between the two groups. Discussion/Conclusion: The COVID-19 pandemic had no effect on the presentation of uveal melanoma patients across all tumor characteristics including size, staging, and gene expression data, suggesting there was not a significant diagnostic delay in care for uveal melanoma patients at our center due to the pandemic.

COVID-related choroiditis masquerading as a choroidal melanoma

In the last two years, considerable attention has focused on eye disorders in the COVID-19 infection. The damage to the inner tunic of the eye is the most dramatic. The authors address hemodynamic abnormalities in these patients occurring during the disease and in the post-COVID-19 syndrome as demonstrated by optical coherence tomography (OCT) and OCT angiography (OCTA). Clinical presentations of COVID-related choroiditis are similar to those of other choroidites. This paper discusses a 66-year-old man with COVID-related choroiditis masquerading as choroidal melanoma who experienced the COVID-infection in April–May 2021. Clinical echographic signs of COVID-related choroiditis are described. The pathomorphology of this condition is uncovered for the first time. By comparing morphological signs in the choroid typical for cell damage with viruses and signatures of the pathological process in the inner tunic of the eye, the disease was interpreted as a COVID-associated choroiditis. The authors conclude that attention should be paid to both early vision loss and its rate when differentiating between tumor-and non-tumor-related choroid disorders. © 2022, Medicine-Inform LLC. All rights reserved.

Early together: A randomized phase III study of early palliative care in metastatic uveal melanoma (MUM)

Background: Uveal melanoma is a rare cancer. Up to 50% of patients (pts) develop metastasis, mainly hepatic. Overall survival in metastatic pts is 12 months (mo), contrasting with a good overall condition until death. To evaluate the impact of integrating early palliative care on patient needs and self-efficacy, we designed a comparative randomized trial in MUM pts. Methods: 162 pts will be randomized (1:2) between the control and the experimental groups in two French centres (Institut Curie-Paris and Centre Antoine Lacassagne-Nice). In the control group, palliative care is introduced according to international guidelines. In the experimental group, it is added earlier, concomitant to the announcement of metastases by the medical oncologist. The main objective is to assess if early supportive care impacts on patient psychological needs at 6 mo, versus standard of care, based on the SCNS-SF34 questionnaire. Secondary objectives include patient's other needs at 6 and 12 mo, quality of life (QLQC30), progression-free and overall survival, and partners' needs (SCNS-P&C). MUM pts, suitable for a treatment with no curative intent, ECOG PS 0-1, with no physical or biological sign of disease, and capable of filling questionnaires are eligible. Questionnaires are completed by all pts at each oncological visit (baseline, 3, 6, 9 and 12 mo). Supportive care visits take place every 6 weeks if needed and address patient's information needs, disease and treatment understanding, social and psychological status, symptoms, and partners' involvement. Prognostic uncertainty and disease seriousness in the absence of symptom is addressed depending on pts' expressed needs. Medical oncologists and supportive care physicians from both centres attend communication skill training provided by an expert during the study. Analyses: SCNS-SF34 psychological needs scale scores at 6-mo will be compared with a Student's t-test, in an ITT analysis. For 10 points mean score difference expected between groups (within standard deviation of 20 points) and a two-sided type 1 error of 5%, inclusion of 54 pts (control group) and 108 pts (experimental group) provides the study 85% of power. The planned inclusion period is 3 years, pts will be followed for one year, for a total study duration of 4 years. From July 2020 to January 2022, 63 pts have been enrolled in the trial;2 pts declined. Five pts were removed early from the study: one for consent retrieval, 4 for early death due to metastasis. COVID-19 delayed enrollment for 5 months. We plan to complete the study Q4 2023 and to analyze the data Q4 2024.

Underlying Ciliary Body Uveal Melanoma in a Patient with Chronic Lymphocytic Leukemia Presenting for Hyphema.

(1) Background: Ciliary body uveal melanoma is a rare subtype of uveal melanoma which comprises 3-5% of melanomas, an immunogenic cancer, and can present multifaceted initial clinical manifestations, masquerading as various ocular pathologies. Chronic lymphocytic leukemia (CLL) presents immunodeficiency and risk for the development of a secondary malignancy, with Bruton's tyrosine kinase inhibitor treatment having a mutagenic effect and a secondary anti-platelet aggregation effect. We present the case of a 65-year-old patient undergoing treatment for CLL with ibrutinib who presented with recurrent hyphema that masked an underlying, inferiorly situated, ciliary body uveal melanoma; (2) Methods: Retrospective case review; (3) Results: An ophthalmological examination together with imaging via mode B ultrasound and contrast-enhanced magnetic resonance imaging resulted in the clinical and imagistic diagnosis of a ciliary body uveal melanoma. A pathological examination of the enucleated eye confirmed the diagnosis. Postoperative tumoral reoccurrence was not detected for 1½ years, however, CLL immunosuppression worsened with admission for severe COVID-19 disease. (4) Conclusions: CLL patient screening for melanoma should also include detailed ophthalmological examinations, which could also include ultrasound ophthalmological imaging. The avoidance of uveal melanoma metastatic disease is paramount for patient survival. CLL manifests additional profound immunosuppression.

Necrosis of uveal melanoma post-COVID-19 vaccination.

A 49-year-old Indian male presented with rapidly progressive vision loss 1 day after receiving the second dose of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine (Pfizer-BioNTech, NY, USA). The eye had secondary angle closure glaucoma, bullous retinal detachment, and massive intraocular hemorrhage. Ultrasound showed an ill-defined subretinal mass with moderate internal reflectivity. Magnetic resonance imaging (MRI) confirmed an enhancing heterogeneous subretinal mass. Histopathology showed a necrotic melanocytic lesion arising from the posterior edge of the ciliary body and choroid. Necrotic uveal melanoma was confirmed after expert histopathology opinion. Uveal melanomas can rarely present with tumor necrosis following mRNA COVID-19 vaccination.

Detecting Progression of Treated Choroidal Melanomas: Is Ultrasonography Necessary?

Prompt detection and treatment of local treatment failure after radiotherapy for choroidal melanoma optimises any opportunities for conserving vision and the eye, possibly reducing an increased risk of metastatic disease. Long-term surveillance is therefore required but is hampered by the perceived need to perform ultrasonography, which may not be available at a patient's local hospital. The aim of this study was to determine whether local treatment failure can reliably be detected with colour fundus photography alone, and, if so, in which patients. Patients were included in the study if diagnosed with local treatment failure between April 2016 and February 2021 after eye-conserving therapy for choroidal melanoma. Wide-field colour and fundal autofluorescence (FAF) images, optical coherence tomography (OCT), and ultrasonography (US) were analysed by two of the authors (GN and UH). The cohort included 87 patients with local treatment failure. In 75 patients with clear media, tumour progression was detected by colour photography alone in 74 (98.7%) patients. Sensitivity was not increased by the addition of either OCT or AF. One patient with clear media developed extraocular extension detected with US without visible change in the intraocular part of the tumour. In the other 12 patients, US was required because of opaque media and a consequently poor fundal view. Local treatment failure after radiotherapy for choroidal melanoma is detected in 98.7% of cases with colour photography when the media are clear. Ultrasonography is useful when photography is prevented by opaque media or tumours having locations in the far periphery.

The Trends of Uveal Melanoma Research in the Past Two Decades and Future Perspectives.

Evaluation of the research trends in uveal melanoma in the past two decades. Data were extracted from the Web of Science database website. VOSviewer and Citespace software were used to analyze the retrieved data. The leading country in terms of output and international collaboration is the USA. Research interest in genetic mutations, molecular pathways, and immunotherapy was remarkable in recent years. Most of the top ten journals are specialized in ophthalmology. In recent years, the hotspots include future perspectives, BAP1 mutation, therapeutic target, and systematic reviews. The keywords with the strongest citation bursts are immunotherapy, outcome, and in situ hybridization. The output of uveal melanoma research increased during the past two decades. Before 2015, the main focus of the research was to facilitate prognostication and metastatic risk stratification. Recently, research has moved to examine the metastatic microenvironment. Future research foci may include exploring the role of different mutations, immunotherapy, molecular alterations, and finding ideal clinical biomarkers.