Ibudilast Protects Retinal Bipolar Cells from Excitotoxic Retinal Damage and Activates the mTOR Pathway.

Ibudilast, an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE), has been recently shown to have neuroprotective effects in a variety of neurologic diseases. We utilize a chick excitotoxic retinal damage model to investigate ibudilast's potential to protect retinal neurons. Using single cell RNA-sequencing (scRNA-seq), we find that MIF, putative MIF receptors CD74 and CD44, and several PDEs are upregulated in different retinal cells during damage.

Two unique BAP1 pathogenic variants identified in the same family by panel cascade testing.

Germline pathogenic variants in the tumor suppressor gene BAP1 are associated with the hereditary tumor predisposition syndrome with susceptibility to uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other cancers. Germline BAP1 pathogenic variants are rare in the non-cancer general population with an estimated carrier frequency of 1:19,898 but more common in cancer patients with a carrier frequency of 1:1299. In the following we present the first report of a family with two unique BAP1 pathogenic variants.

Exploring approaches for predictive cancer patient digital twins: Opportunities for collaboration and innovation.

We are rapidly approaching a future in which cancer patient digital twins will reach their potential to predict cancer prevention, diagnosis, and treatment in individual patients. This will be realized based on advances in high performance computing, computational modeling, and an expanding repertoire of observational data across multiple scales and modalities. In 2020, the US National Cancer Institute, and the US Department of Energy, through a trans-disciplinary research community at the intersection of advanced computing and cancer research, initiated team science collaborative projects to explore the development and implementation of predictive Cancer Patient Digital Twins.

Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.

Introduction: Approximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.

Ultra-wide field imaging to assess the optic nerve and retina in Boston type I and II keratoprosthesis patients.

Background: The ability to view the posterior segment in keratoprosthesis (Kpro) implanted patients is limited. The purpose of this retrospective, observational study was to investigate the use of ultra-wide field (UWF) scanning laser ophthalmoscopy imaging and its utility for serial evaluation of the retina and optic nerve in patients with either a Boston type I or II Kpro.

Methods: A retrospective chart review was performed for patients with a Boston type I or II Kpro seen at The Ohio State University Wexner Medical Center.

Choroidal Effusion Mimicking Uveal Melanoma: A Novel Presentation of Idiopathic Systemic Capillary Leak Syndrome.

Background: Idiopathic systemic capillary leak syndrome (ISCLS, also known as Clarkson's disease) is a rare medical condition characterized by episodes of capillary endothelial cell dysfunction with leakage of fluid into the interstitial space resulting in severe hypotension, hemoconcentration, hypoalbuminemia, and generalized edema. Each episode can result in multiorgan failure due to systemic hypoperfusion.

Case Presentation: We report a case of uveal effusion, mimicking uveal melanoma, associated with ISCLS following viral infection.

A Mathematical Model of Breast Tumor Progression Based on Immune Infiltration.

Breast cancer is the most prominent type of cancer among women. Understanding the microenvironment of breast cancer and the interactions between cells and cytokines will lead to better treatment approaches for patients. In this study, we developed a data-driven mathematical model to investigate the dynamics of key cells and cytokines involved in breast cancer development.

Estrogen Receptor Is Expressed in Uveal Melanoma: A Potential Target for Therapy.

Background: Metastatic uveal melanoma (UM) has no effective treatment. To date, no publications have reported immunohistochemical evidence of estrogen receptors (ERs) in UM; however, changes in pathologic reporting for ER in breast carcinoma prompted a re-examination of ER in UM, as it could represent a potential therapeutic target.

Objective: To determine if UM tumors express ER by immunohistochemistry (IHC) using current methodology for breast cancer and to evaluate ER gene expression using a publicly available UM database.

Is Uveal Melanoma a Hormonally Sensitive Cancer? A Review of the Impact of Sex Hormones and Pregnancy on Uveal Melanoma.

Background: Despite a higher incidence and worse prognosis of uveal melanoma (UM) in men, there have been many case reports of pregnant patients with aggressive UM. This has led researchers to explore the influence of sex hormones and pregnancy on the development and progression of UM and hormones as potential therapeutic targets.

Summary: A systematic literature review was conducted.

Multimodal imaging and functional analysis of the chick NMDA retinal damage model.

Objectives: The chick is rapidly becoming a standardized preclinical model in vision research to study mechanisms of ocular disease. We seek to comprehensively evaluate the N-methyl-D-aspartate (NMDA) model of excitotoxic retinal damage using multimodal imaging, functional, and histologic approaches in NMDA-damaged, vehicle-treated, and undamaged chicks.

Methods: Chicks were either left undamaged in both eyes or were injected with NMDA in the left eye and saline (vehicle) in the right eye.

TMEM97 ablation aggravates oxidant-induced retinal degeneration.

The retinal pigment epithelium (RPE) is critical to the survival of the overlying photoreceptors. Subject to light exposure and active metabolism, the RPE and photoreceptors are particularly susceptible to oxidative damage that plays an important part in age-related macular degeneration (AMD). Recent meta-analyses identified TMEM97 as a new putative AMD risk locus, though it is yet to be functionally verified.

Intraocular metastases of lung origin: Case reports and cytology correlates.

Intraocular metastases from the lung are a common occurrence and an important differential for cytopathologists reading fine needle aspiration biopsies (FNAB). It is a particularly challenging diagnosis when the patient has had no previous diagnosis of lung cancer. We present two cases of intraocular metastases from lung primaries, and we discuss the clinical, radiological, and cytopathological features that help differentiate intraocular metastases of lung primary from other intraocular tumours, in the setting of FNAB.

Atypical choroidal nevus in a subject with a germline PALB2 pathogenic variant.

Recent evidence suggests that PALB2 variants may increase risk for the development of uveal melanoma and uveal melanocytic neoplasms. Here we report a case of an atypical choroidal nevus in a patient with a personal history of cancer and pathogenic PALB2 germline variant. A 75-year-old white female presented with an elevated predominantly amelanotic choroidal lesion OS.

Isolated Diffuse Choroidal Hemangioma: A Variant of Sturge-Weber Syndrome?

The authors report a case of a diffuse choroidal hemangioma in the left eye of a 17-year-old girl. No evidence of leptomeningeal angiomatosis was found on magnetic resonance imaging and neither the medical history nor the clinical examination revealed a port wine birthmark on the left side of the face. Fine telangiectatic vessels were found on the bulbar conjunctiva of the ipsilateral eye.

Uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year.

Whole Exome Sequencing Identifies Candidate Genes Associated with Hereditary Predisposition to Uveal Melanoma.

Purpose: To identify susceptibility genes associated with hereditary predisposition to uveal melanoma (UM) in patients with no detectable germline BAP1 alterations.

Design: Retrospective case series from academic referral centers.

Participants: Cohort of 154 UM patients with high risk of hereditary cancer defined as patients with 1 or more of the following: (1) familial UM, (2) young age (<35 years) at diagnosis, (3) personal history of other primary cancers, and (4) family history of 2 or more primary cancers with no detectable mutation or deletion in BAP1 gene.

Heterogeneity in Mitogen-Activated Protein Kinase (MAPK) Pathway Activation in Uveal Melanoma With Somatic GNAQ and GNA11 Mutations.

Purpose: The activation of the mitogen-activated protein kinase (MAPK) pathway has been suggested as the major downstream target when GNAQ and GNA11 (GNAQ/11) are mutated in uveal melanoma (UM). However, clinical trials with single agent MEK inhibitor showed no clinical significance in altering the overall outcome of the disease in UM; therefore, we investigated the correlation between naturally occurring mutations in GNAQ/11 and activation of MAPK pathway in vivo in primary UM.

Methods: Screening for activating mutations in codons 183 and 209 of GNAQ/11 was carried out by sequencing and restriction fragment length polymorphism (RFLP) in a cohort of 42 primary UM.

Germline large deletion of BAP1 and decreased expression in non-tumor choroid in uveal melanoma patients with high risk for inherited cancer.

Uveal melanoma (UM) is the most common phenotype in patients with germline BAP1 mutation. This study aimed to identify selection criteria for BAP1 germline testing and assessed the role of large deletion/duplication and epigenetic inactivation. One hundred seventy-two UM patients with high risk of hereditary cancer were included.